Dermatology

How to Boost Your Immune System While Living With Psoriasis – Everyday Health

Your immune system is made up of cells, tissues, and organs that help your body stay healthy and fight infections. But when you have psoriasis, your immune system doesnt always work the way it should.

Psoriasis revs up your immune system like theres something that its trying to fight, but theres actually nothing there, says Anne Truitt, MD, a dermatologist at Skin Surgery Medical Group in San Diego. The resulting inflammation in your body leads to psoriasis symptoms such as skin plaques, according to the National Psoriasis Foundation (NPF).

Due to the nature of psoriasis, some of the medications used to treat it are also designed to affect the way your immune system works. Because psoriasis is a condition where the immune system is upregulated, when we use medicines to downregulate the immune system, the medications that treat psoriasis can decrease your immunity, says Marisa Garshick, MD, an assistant clinical professor of dermatology at NewYork-Presbyterian Weill Cornell Medical Center and dermatologist at MDCS Dermatology in New York City.

This is especially true of systemic drugs, such as methotrexate. Those drugs tamp down the entire immune system to slow down psoriasis. Newer drugs such as biologics act on the immune system in a different way. Because they only target specific immune cells or proteins linked to psoriasis, they dont affect the rest of the immune system the way systemic drugs do. That said, Some biologics may carry an increased risk of certain types of infections, based on the particular cytokine or marker that they are decreasing, Dr. Garshick says.

Treatment options such as topical medications dont tend to affect the immune system as much, either, because they arent ingested or administered inside the body.

No matter which medication you take, its good to keep your immune system working as well as it can. Heres how to do just that.

You may wonder if you need to do anything special to improve your immunity, especially in the colder months. I think its important for everybody to boost their immune system during cold and flu season. But its also well documented in literature that psoriasis patients are at a higher risk of catching the flu than the average person, says Dr. Truitt. This is especially true for those who take systemic medication.

The good news? Taking measures to prevent infections can not only help you stay healthy but also lower the frequency and severity of psoriasis flares. Start with these strategies.

Even though COVID-19 has died down, washing hands is still key to cutting down the risk of any infection. And for people with compromised immunity, proper handwashing can reduce the incidence of colds by up to 21 percent, according to research published in the Annals of Translational Medicine.

Wash your hands before and after eating or preparing food, after coughing or blowing your nose, after using the toilet, and when you arrive somewhere new.

Because psoriasis patches tend to be dry, opt for handwashing instead of hand sanitizers whenever possible. Stay away from sanitizers that have a lot of alcohol or drying components to it, Truitt advises. And then make sure that youre moisturizing with a bland moisturizer after drying your hands.

Just 31 percent of people with psoriasis got the flu vaccine during the 20182019 season, even though it was recommended to almost all of them, according to one study. This may be in part because people worry that the vaccine will trigger their immune system and lead to a psoriasis flare. But the opposite may be true, according to another study. Researchers found that people with moderate-to-severe psoriasis benefit from influenza, pneumococcal, and shingles vaccines.

Talk to your doctor about which vaccines are recommended for you, based on your age and vaccine history.

There are countless benefits to exercise, including better immunity. Research has found that regular physical activity can prepare and strengthen the immune system against communicable diseases such as COVID-19.

Theres also definitely a strong correlation between regular exercising and reducing your psoriasis flares, says Truitt. Exercise also helps reduce the comorbidities associated with psoriasis like obesity, diabetes, and cardiovascular issues.

Exercising regularly can also help with losing weight or maintaining a healthy weight. Doing so helps reduce inflammation in the body, which can improve psoriasis and reduce the risk of these comorbidities.

To both strengthen your immune system and reduce inflammation in your body, stick to an anti-inflammatory diet, suggests the University of Pittsburgh Medical Center. This includes plenty of:

You should also limit your intake of processed, packaged, and sugary foods, such as fried foods, processed meats, chips, and cookies.

Almost 90 percent of people with psoriasis have trouble sleeping, according to researchers at the University of California in San Francisco. When youre flaring and itchy, it can be hard to sleep. Unfortunately, lack of sleep is tied to poorer immunity.

To get the best rest possible, practice good sleep hygiene by sticking to a regular sleep-wake schedule and keeping your bedroom cool, quiet, and free of electronics. Talk to your doctor about other strategies that might help, based on your individual circumstances.

Research suggests people with psoriasis may have low vitamin D levels. Its not only linked to immunity. Vitamin D is essential for healthy skin. It calms inflammation and helps normalize skin turnover, says Truitt.

To get more vitamin D, eat dairy, fish, and soy alternatives fortified with the vitamin, or talk to your doctor about supplements. Spending time outdoors can help you absorb some vitamin D from the sun, too, which may also improve the appearance of psoriasis skin. Just be sure to limit your time in the sunshine and wear sunscreen.

A healthy lifestyle can go a long way toward helping your immunity and your psoriasis. If you have any concerns about infections, its always best to speak with your doctor to determine the specific risks related to your particular [psoriasis] medication, says Garshick.

Your doctor may be able to switch you to another medication that will manage flares without affecting immunity.

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How to Boost Your Immune System While Living With Psoriasis - Everyday Health

Dermatology

Cosmetic Procedures for Psoriasis: Are They Safe? – Everyday Health

If youre used to buying fragrance- and chemical-free makeup and moisturizers, you might have assumed that facials, fillers, and other cosmetic procedures are also off the table.

But, as it turns out, people with psoriasis dont necessarily have to avoid beauty treatments as long as the psoriasis is under control. Active disease states are very inflammatory, and inflammation increases the likelihood of things not going well, says Sonya Kenkare, MD, a dermatologist at the Illinois Dermatology Institute in Hinsdale.

Thats not all you need to keep in mind. Psoriasis is known to be aggravated by skin trauma, says Joel M. Gelfand, MD, director of the Psoriasis and Phototherapy Treatment Center at Penn Medicine in Philadelphia. Psoriasis lesions can form after your skin has been injured by a burn, for example, or a cut, which is called the Koebner phenomenon.

This is why many people who have psoriasis assume theyll never be candidates for any type of beauty treatment: They believe lasers, peels, and needles will cause trauma to the skin. But if your psoriasis is under control, you likely wont experience a flare-up of symptoms after getting a cosmetic procedure, says Dr. Kenkare.

In a study published in 2020, about nine out of 10 of people with moderate-to-severe psoriasis whod undergone a cosmetic procedure said they were able to do so because they started taking a treatment that alleviated most of their lesions. The majority of the studys participants said their psoriasis had prevented them from these types of procedures previously.

Still, if you want to try a treatments, its better to talk to a dermatologist first to find out if youre a candidate, says Dr. Gelfand.

Heres what you should know about some of the more common cosmetic procedures.

What they are:These neurotoxin injections block the nerve signals to the muscles, which temporarily prevents them from tensing, according to Cleveland Clinic. The injections are used to smooth fine lines and wrinkles, often in the face and neck.

Risks:You may experience some swelling, redness, or bruising at the injection sites, but this is usually mild and improves in a day or so.

How to do it safely:Your doctor may recommend avoiding nonsteroidal anti-inflammatory drugs (NSAIDs) for a day or two before the procedure, because they can increase the risk of bruising, according to Cleveland Clinic. So can alcohol, meaning you may want to abstain from drinking for 24 hours before your appointment.

What they are: Treatments depend on the type of facial you get and the skin-care specialist doing it. But in general, they include a facial cleanser, exfoliation to remove dead skin cells, moisturizer, and a gentle massage.

Risks: Sometimes, facials can cause skin purging an acceleration of your skins natural cell turnover, which can cause breakouts.

How to do it safely: Ask your aesthetician to use gentle moisturizers and other skin-care products that wont irritate your skin, especially if you know certain ingredients trigger your symptoms.

What it is: This procedure uses a beam of light to vaporize the hair within the follicle, according to the American Academy of Dermatology Association (AAD). When done correctly, it shouldnt cause trauma to the skin itself, says Kenkare. Lasers can remove hair from any part of your body, but its most commonly used on the bikini line, face, legs, and underarms.

Risks: If you dont go to a pro, such as a dermatologist, its possible to experience side effects such as blistering and scarring.

How to do it safely: In the days after treatment, youll want to stay out of the sun, since ultraviolet (UV) rays can further damage your already sensitive skin.

What it is: Thin needles are used to make tiny holes in the skin in this procedure. This stimulates the production of collagen, a protein that helps keep skin smooth, according to Cleveland Clinic. Its often done on the face, but microneedling can also be done on the back, legs, neck, and other areas of the body.

Risks: There can be some redness and discomfort after microneedling, according to the AAD.

How to do it safely: Avoid using at-home microneedling products, which could pierce the skin and cause scarring or infection, according to the AAD. Before you have microneedling, you may need to avoid alcohol, NSAIDs, and products that contain salicylic acid for a day or so.

What it is: This treatment uses a device to gently remove the top layer of skin, which gives the skin a smoother appearance, according to the AAD. It may feel as if someone is sanding your skin, but it isnt painful. Microdermabrasion is performed to lessen age spots, fine lines or wrinkles, and mild scars. Its often done on the face, but you can get microdermabrasion on other areas of the body, such as the back, chest, hands, and neck, as well.

Risks: After microdermabrasion, there can be some redness or swelling, similar to a sunburn.

How to do it safely: You may need to avoid taking NSAIDs and using products that contain salicylic acid for a few days before your scheduled microdermabrasion. If you use products that contain other irritating ingredients, such as glycolic acid or retinols, you may need to stop taking them for at least a week before the procedure, according to Cleveland Clinic.

Before you undergo a cosmetic procedure, talk to a dermatologist who has experience working with people who have psoriasis, and ask whether the procedure is right for you.

The best time for psoriasis patients to do cosmetic procedures is when the psoriasis is under good control, says Kenkare. If a persons overall inflammation is otherwise well controlled it should be well tolerated.

Whether you go to a dermatologist or another professional like an aesthetician or cosmetologist be sure to let them know about your psoriasis. That way, they can take any extra precautions to avoid irritating your skin.

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Cosmetic Procedures for Psoriasis: Are They Safe? - Everyday Health

Dermatology

Im a Harvard-trained dermatologist Ive followed 3 anti-aging rules for years, Im still a fan of a drug… – The US Sun

A DERMATOLOGIST has given his best advice for keeping the largest organ in the body in its best condition.

He said there are three rules to live by for skincare, plus an anti-aging serum he swears by.

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Dr. Daniel Sugai (@drspf) filmed himself discussing the tips in a viral video on TikTok.

He said he adopted the three skincare steps after completing his dermatology residency.

Dr. Sugai also gave several options to get the best benefits from certain products.

He added that one skincare staple in particular was a game changer.

Dr. Sugai advised using retinoids, saying he first started using them during his residency.

However, he admitted he was inconsistent with his use of the product due to the time constraints that came with his medical training.

First, he recommended the Olay Regenerist Retinol, $27.15, available on Amazon.

He also suggested using Cerave's Resurfacing Retinol Serum for any dark spots left behind.

The serum is currently on sale on Amazon for $12.55.

Finally, he shared his love for RoC Retinol Correxion Anti-Aging Night Serum capsules for easy skincare on the go.

He said that they help with signs of aging and that he uses the drugstore serum to this day while traveling.

Dr. Sugai also advocated for a skincare staple sunscreen.

He said that no matter if he plans on being in direct sunlight or not, he always wears sunscreen.

The dermatologist added that using an SPF is also a good way to combat hyperpigmentation.

He is a fan of the Cerave Hydrating Mineral Sunscreen, $13.84, available on Amazon.

Dr. Sugai said a certain serum he started using in his late 20s brightened his complexion.

*If you click on a link in this article, we may earn affiliate revenue.

He recommended the Obagi Medical 15% Serum, $115.

He explained that it is an antioxidant that helps fight free radicals from pollution and other sources.

The anti-aging properties of vitamin C also kept his complexion looking bright and youthful.

A 2017 study by experts classifies topical vitamin C as "one of the most powerful antioxidants in the skin."

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Im a Harvard-trained dermatologist Ive followed 3 anti-aging rules for years, Im still a fan of a drug... - The US Sun

Genetics

Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease – Nature.com

Ethics

Our research complies with all relevant ethical regulations. All studies included in this research were approved by the relevant board or committee. UK Biobank has approval from the North West Multi-centre Research Ethics Committee (REC reference 13/NW/0157) as a Research Tissue Bank (RTB) approval, and informed consent was provided by each participant. This approval means that researchers do not require separate ethical clearance and can operate under RTB approval. This RTB approval was granted initially in 2011 and is renewed every 5 years; hence, UK Biobank successfully renewed approval in 2016 and 2021. The MCPS was approved by the Mexican Ministry of Health, the Mexican National Council for Science and Technology and the University of Oxford. The PGR study was approved by the institutional review board at the Center for Non-Communicable Diseases (IRB: 00007048, IORG0005843, FWAS00014490) and all participants provided informed consent. The SCOOP cohort was approved by the Multi-regional Ethics Committee and the Cambridge Local Research Ethics Committee (MREC 97/21 and REC number 03/103). Participants (or parents for individuals <16 years old) provided written informed consent; minors provided oral consent. The INTERVAL study received ethics committee approval from the National Research Ethics Service Committee (11/EE/0538), and all participants provided informed consent before joining the study.

We used the same processing strategies as those outlined in our previous paper to analyze the WES data and perform quality control steps19. We queried WES data from 454,787 individuals in UK Biobank39, excluding those with excess heterozygosity, those with autosomal variant missingness on genotyping arrays of 5%, or those not included in the subset of phased samples as defined by Bycroft et al.13.

WES data were stored as population-level variant call format (VCF) files, aligned to GRCh38 and accessed through the UK Biobank Research Analysis Platform (RAP). In addition to the quality control measures already applied to the released data, as described by Backman et al.39, we conducted several additional quality control procedures. First, we used bcftools v1.14 norm40 to split the multiallelic sites and left-correct and normalize indels. Next, we filtered out variants that failed our quality control criteria, including those with: (1) read depth of <7; (2) genotype quality of <20; and (3) binomial test P value for alternative allele reads versus reference allele reads of 0.001 for heterozygous genotypes. For indel genotypes, we kept only variants with read depth of 10 and genotype quality of 20. Variants that failed quality control criteria were marked as missing (that is, ./.). After filtering, variants where more than 50% of the genotypes were missing were excluded from downstream analyses19.

The remaining variants underwent annotation using Ensembl Variant Effect Predictor (VEP v104)41 with the -everything flag and additional plugins for REVEL14, CADD42 and LOFTEE43. For each variant, a single Ensembl transcript was prioritized on the basis of whether the annotated transcript was protein-coding, MANE select v0.97 (ref. 44) or the VEP canonical transcript. The individual consequence for each variant was then prioritized on the basis of severity as defined by VEP. Stop-gained, splice acceptor and splice donor variants were merged into a combined PTV category, while annotations for missense and synonymous variants were adopted directly from VEP. We included only variants on autosomes and the X chromosome that were within Ensembl protein-coding transcripts and transcripts included in the UK Biobank WES assay in our downstream analysis.

Our analyses focused primarily on individuals of European genetic ancestry, and we excluded those who withdrew consent from the study, resulting in a final cohort of 419,668 individuals.

We used BOLT-LMM v2.3.6 (ref. 15) as our primary analytical tool to conduct the gene-burden test. To run BOLT-LMM, we first queried a set of genotypes with minor allele count (MAC) >100, which was derived from the genotyping arrays for the individuals with the WES data to build the null model. To accommodate BOLT-LMMs requirement for imputed genotyping data rather than per-gene carrier status, we developed dummy genotype files in which each gene was represented by a single variant. We then coded individuals with a qualifying variant within a gene as heterozygous, regardless of the total number of variants they carried in that gene. We then created dummy genotypes for the HC PTVs with MAF < 0.1% as defined by LOFTEE, missense variants with REVEL >0.5 and missense variants with REVEL >0.7. We then used BOLT-LMM to analyze phenotypes using default parameters, except for the inclusion of the lmmInfOnly flag. In addition to the dummy genotypes, we included all individual markers in the WES data to generate association test statistics for individual variants. We used age, age2, sex and the first ten principal components (PCs) as calculated by Bycroft et al.13 and the WES release batch (50k, 200k, 450k) as covariates.

To check whether there was a single variant driving the association, we performed a leave-one-out analysis for BSN and APBA1 using linear regression in R v3.6.3 by dropping the HC PTVs contained in our analysis one by one. In addition, we also checked the geographic distribution of APBA1 and BSN HC PTV carriers.

We sought replication of our findings for the four new genes in two independent predominantly non-European exome-sequenced cohorts: the MCPS and the PGR study.

MCPS is a cohort study of 159,755 adults of predominantly admixed American ancestry. Participants aged 35 years or older were recruited between 1998 and 2004 from two adjacent urban districts of Mexico City. Phenotypic data were recorded during household visits, including height, weight, and waist and hip circumferences. Disease history was self-reported at baseline, and the participants were linked to Mexican national mortality records. The cohort has been described in detail elsewhere17,18.

The PGR study has been recruiting participants aged 15100 years as cases or controls via clinical audits for specific conditions since 2005 from over 40 centers around Pakistan. Participants were recruited from clinics treating patients with cardiometabolic, inflammatory, respiratory or ophthalmological conditions. Information on lifestyle habits, medical and medication history, family history of diseases, exposure to smoking and tobacco consumption, physical activity, dietary habits, anthropometry, basic blood biochemistry and electrocardiogram traits was recorded during clinic visits. DNA, serum, plasma and whole blood samples were also collected from all study participants.

Exome sequencing data for 141,046 MCPS and 37,800 PGR participants were generated at the Regeneron Genetics Center and passed Regenerons initial quality control, which included identifying sex discordance, contamination, unresolved duplicate sequences and discordance with microarray genotype data for MCPS. Genomic DNA was subjected to paired-end 75-bp WES at Regeneron Pharmaceuticals using the IDT xGen v1 capture kit on the NovaSeq 6000 platform. Conversion of sequencing data in BCL format to FASTQ format and the assignments of paired-end sequence reads to samples were based on 10-base barcodes, using bcl2fastq v2.19.0.

These exome sequences were processed at AstraZeneca from their unaligned FASTQ state. A custom-built Amazon Web Services cloud computing platform running Illumina DRAGEN Bio-IT Platform Germline Pipeline v3.0.7 was used to align the reads to the GRCh38 genome reference and perform single-nucleotide variant (SNV) and insertion and deletion (indel) calling. SNVs and indels were annotated using SnpEff v4.3 (ref. 45) against Ensembl Build 38.92. All variants were additionally annotated with their gnomAD MAFs (gnomAD v2.1.1 mapped to GRCh38)43.

To further apply quality control to the sequence data, all MCPS and PGR exomes underwent a second screening using AstraZenecas bioinformatics pipeline, which has been described in detail previously46. Briefly, we excluded from the analysis sequences that had a VerifyBamID freemix (contamination) level of more than 4%, those for which inferred karyotypic sex did not match self-reported gender or those for which less than 94.5% of the consensus coding sequence (CCDS release 22) achieved a minimum tenfold read depth. We further removed one individual from every pair of genetic duplicates or monozygotic twins with a kinship coefficient of >0.45. Kinship coefficients were estimated from exome genotypes using the kinship function from KING v2.2.3 (ref. 47). For the MCPS, we additionally excluded sequences with an average CCDS read depth of at least 2 s.d. below the mean. After the above quality control steps, 139,603 (99.0%) MCPS and 37,727 (99.3%) PGR exomes remained.

For the MCPS, we predicted the genetic ancestry of participants using PEDDY v0.4.2 (ref. 48), with 1000 Genomes Project sequences as population ref. 49, and retained individuals with a predicted probability of admixed American ancestry of 0.95 who were within 4 s.d. of the means for the top four PCs. In the PGR study, we retained individuals with a predicted probability of South Asian ancestry of 0.95 who were within 4 s.d. of the means for the top four PCs. Following ancestry filtering, 137,059 (97.2%) MCPS and 36,280 (95.5%) PGR exomes remained.

We assessed the association of BMI and weight quantitative traits with genotype at the four proposed new genes of interest using a previously described gene-level collapsing analysis framework implementing a PTV collapsing analysis model46. We classified variants as PTVs if they had been annotated by SnpEff as follows: exon_loss_variant, frameshift_variant, start_lost, stop_gained, stop_lost, splice_acceptor_variant, splice_donor_variant, gene_fusion, bidirectional_gene_fusion, rare_amino_acid_variant and transcript_ablation.

We applied MAF filters to target rare variants: MAF <0.001 in gnomAD (overall and every population except OTH) and leave-one-out MAF <0.001 among our combined case and control test cohort. For variants to qualify, they had to also meet the following quality control filters: minimum site coverage of 10; annotation in CCDS transcripts (release 22); at least 80% alternative reads in homozygous genotypes; a percentage of alternative reads for heterozygous variants of 0.25 and 0.8; a binomial test of alternative allele proportion departure from 50% in the heterozygous state result of P >1106; GQ of 20; FS of 200 (indels) or 60 (SNVs); MQ of 40; QUAL of 30; read position rank sum score of 2; MQRS of 8; DRAGEN variant status =PASS; and test cohort carrier quality control failure of <0.5%. If the variant was observed in gnomAD exomes, we also applied the following filters: variant site achieved tenfold coverage in 25% of gnomAD exomes; variant site achieved exome z-score of 2.0; exome MQ of 30; and random forest probability that the given variant is a true SNV or indel of >0.02 and >0.01, respectively50.

For the quantitative traits and for each gene, the difference in mean between the carriers and noncarriers of PTVs was determined by fitting a linear regression model, correcting for age and sex. In addition to calculating individual statistics for the MCPS and the PGR study, we also meta-analyzed the individual study effect sizes to generate a combined replication statistic using an inverse variance-weighted fixed-effect meta-analysis using the rma.uni() function from the metafor package v3.8-1 (ref. 51) in R v3.6.3.

To test whether there was an association between pLOF variants in the BSN gene and severe early-onset obesity, we studied 927 exomes from white British participants with severe early-onset obesity recruited to the Genetics of Obesity Study (GOOS) (SCOOP cohort) and 4,057 control exomes from the INTERVAL cohort of UK blood donors. SCOOP comprises UK patients with severe obesity (BMI more than 3 s.d. above the mean for age and sex) of early onset (<10 years) recruited to the GOOS. Exome sequencing in a subset of people of white British ancestry (the SCOOP cohort) was performed as described previously52,53,54. INTERVAL comprises predominantly healthy blood donors in the UK55 (https://www.intervalstudy.org.uk).

SCOOP and INTERVAL variants were joint-called and filtered for variant-level and sample-level quality control, as previously described52. A total of 927 cases (SCOOP) and 4,057 controls (INTERVAL) passed the quality control filters53. After splitting multiallelic variants and left normalizing, we annotated variants using VEP with Ensembl v96 (GRCh37) and identified high-impact variants (predicted protein-truncating, null or splice-disrupting) in the gene BSN (transcript ENST00000296452) using VEP IMPACT=HIGH. This definition includes stop-gain variants (SNVs resulting in stop codons), frameshifts and splice donor/acceptor variants. We verified that the predicted consequences and stop codon positions were maintained in the latest minor version of the transcript (ENST00000296452.5, NM_003458.4) using VEP v110 after lifting over to GRCh38. Missense variants were detected in almost all BSN exons among SCOOP exomes (7/10 coding exons) and INTERVAL exomes (8/10 coding exons), suggesting that BSN stop-gain detection rates in cases and controls are unlikely to be driven by differential read coverage within the BSN gene.

The one PTV identified in INTERVAL (p.Trp3926*) is located at the final amino acid of the bassoon protein and is therefore unlikely to affect expression levels (note that the LOFTEE in silico stop-gain filter for low-confidence loss of function based on the 50-bp rule does not apply to the BSN gene because the termination codon is itself >55 bp from the final exonexon boundary56). After excluding this variant on the basis of low confidence for loss of function, we performed a nested gene-burden analysis on the remaining three variants: n =3 pLOF carriers in SCOOP and n =0 carriers in INTERVAL controls (OR (95% CI) = inf (1.8inf), P =0.006, Fishers exact test; adding +0.5 to each cell, OR =31). Studies in vitro are required to establish the effect of each stop-gain variant on bassoon protein expression levels and localization.

We included binary and quantitative traits made available in the June 2022 UK Biobank data release, harmonizing the phenotype data as previously described46. This resulted in 11,690 phenotypes for analysis, which are available on https://azphewas.com. On the basis of clinical relevance, we derived three additional phenotypes.

For UK Biobank phenome-wide analyses of the four putatively new genes, the same data generation and quality control processes described for the MCPS and PGR study were applied to UK Biobank exomes. Following the Regeneron and AstraZeneca quality control steps, 445,570 UK Biobank exomes remained. The phenome-wide analysis was performed in UK Biobank participants of predominantly European descent, whom we identified based on a PEDDY-derived predicted probability of European ancestry of 0.95 and were within 4 s.d. of the means for the top four PCs. On the basis of predicted ancestry pruning, 419,391 UK Biobank exomes were included in the phenome-wide analyses of the four prioritized genes.

As described previously, we assessed the association of the 11,693 phenotypes with genotypes at the four genes of interest, using a PTV collapsing analysis model46, and classifying variants as PTVs using the same SnpEff definitions as described for the MCPS and PGR analyses. For variants to qualify for inclusion in the model, we applied the same MAF and quality control filters used in the MCPS and PGR analyses, with the exception that due to the larger sample size of UK Biobank, only <0.01% of the test cohort carriers were permitted to fail quality control.

We ran association tests of APBA1 and BSN HC PTV carriers and carriers of a BMI-associated common variant (rs9843653) at the BSN locus with a list of anthropometric phenotypes available in UK Biobank using R v3.6.3 (Supplementary Table 5), including the same covariates we used in our exome-wide gene-burden tests. We acquired normalized protein expression data generated by the Olink platform from the UK Biobank RAP23,24. The detailed Olink proteomics assay, data processing and quality control were described by Sun et al.23. For the association tests of APBA1 and BSN PTV carriers and BMI-associated common variant (rs9843653) at the BSN locus carriers with expression levels for 1,463 proteins, we added age2, agesex, age2sex, Olink batch, UK Biobank center, UK Biobank genetic array, number of proteins measured and the first 20 genetic PCs as covariates, as suggested by Sun et al.23. We chose the Bonferroni-corrected P value (P <3.42105 (0.05/1,463)) as the threshold for significance.

Identified genes were queried for proximal BMI GWAS signals, using data from UK Biobank, for signals within 500 kb upstream of the genes start site to 500 kb downstream of the genes end site. Such signals were further replicated in an independent BMI GWAS9.

We also performed colocalization tests, using the approximate Bayes factor method in R v4.0.2 using the package coloc v5.1.0 and blood gene expression data from the eQTLGen study16. Genomic regions were defined as the regions 500 kb around each gene, and loci exhibiting an H4 posterior probability of >0.5 were considered to show evidence of colocalization.

Finally, we used the GWAS data to calculate gene-level common variant associations, using MAGMA v1.09 (ref. 57). To do this, we used all common but nonsynonymous (coding) variants within a given gene. Gene-level scores were further collapsed into pathway-level associations where appropriate.

To examine whether there is an interaction effect between PTV carrier status for BSN and APBA1 and the PGS, we included an interaction term between the PGS and the carrier status for BSN and APBA1 PTVs in a linear regression model adjusted for sex, age and age2, and the first 10 PCs.

The PGS was constructed for 419,581 individuals of white European ancestry who had both genotype and exome sequencing data and a BMI record in UK Biobank. We used summary statistics of BMI from Locke et al.9, which included samples not in UK Biobank. Data were downloaded from the GIANT consortium. The summary statistics included 2,113,400 single-nucleotide polymorphisms (SNPs) with at least 500,000 samples in a cohort of 322,154 participants of European ancestry. For the genotype data of UK Biobank participants, a light quality check procedure was applied, where SNPs were removed if they had a MAF of <0.1%, HardyWeinberg equilibrium P <110-6 or more than 10% missingness. In addition, SNPs that were mismatched with those in the summary statistics (with the same rsID but different chromosomes or positions) were excluded. We used the package lassosum v4.0.5 (ref. 58) in R v3.6.0 to construct the PGS. The R2 of the model including the PGS regressed on rank-based inverse normal-transformed BMI and adjusted for sex, age and age2, and the first 10 PCs as covariates was 11%.

A detailed description of the methods used in cellular work and single-cell analyses can be found in the Supplementary Note.

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.

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Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease - Nature.com

Genetics

Right-wing authoritarianism appears to have a genetic foundation – PsyPost

New research provides evidence that political leanings are more deeply intertwined with our genetic makeup than previously thought, specifically linked to two core ideological traits: right-wing authoritarianism and social dominance orientation. Unlike the conventional belief that our political stances are merely extensions of our personality traits, this study suggests that our views on hierarchy and social dominance have their own distinct genetic foundations. The findings have been published in the Journal of Personality.

Right-wing authoritarianism and social dominance orientation are two psychological constructs that have been extensively studied in the context of political attitudes and behaviors.

Right-wing authoritarianism is characterized by three broad attitudes: submission to authorities perceived as established and legitimate, aggression toward individuals or groups that are seen as deviant or dissenting from perceived societal norms, and adherence to conventional norms and values of the society. People high in right-wing authoritarianism tend to value order, tradition, and national unity, showing strong support for authorities that enforce these principles.

Social dominance orientation, on the other hand, reflects an individuals preference for inequality among social groups. This orientation is about the extent to which individuals desire and support hierarchical relationships between groups, believing that some groups are inherently superior to others. Those with high social dominance orientation are more likely to support policies and practices that maintain these disparities, including discrimination against perceived lower-status groups.

Previous research has established that both right-wing authoritarianism and social dominance orientation are powerful predictors of political attitudes and behaviors, independently of the Big Five personality traits. However, the extent to which these ideological traits are influenced by genetics, as opposed to environmental factors such as socialization, has been less clear.

To explore the underpinnings of political attitudes and their relationship with personality traits, researchers from the Norwegian Institute of Public Health and the University of Oslo analyzed data collected from a sample of 1,987 twins registered in the Norwegian Twin Registry, encompassing individuals born between 1945 and 1960.

The methodological core of the study relied on the classical twin design, which compares the similarities between monozygotic twins, who share virtually all their genes, and dizygotic twins, who share about half of their segregating genes. This approach allowed the researchers to distinguish genetic influences from environmental factors.

The participants completed validated measures of the Big Five personality traits (openness, conscientiousness, extraversion, agreeableness, and neuroticism), right-wing authoritarianism, and social dominance orientation. To gauge political policy attitudes, the researchers developed an index based on four specific items. These items were measured on a 7-point Likert scale ranging from 3 (against) to +3 (support) and included attitudes towards deporting the Roma, reducing aid for developing countries, accepting more asylum seekers (reversed), and implementing strict immigration control.

The researchers found that the covariation between ideological traits and policy attitudes related to national resources and immigration was predominantly explained by genetic factors. This genetic overlap implies that the propensity towards certain political views, especially those concerning hierarchy and authority, can be significantly influenced by ones genetic makeup.

In contrast, the Big Five personality traits, while influential in shaping individuals general attitudes and behaviors, have a comparatively lesser genetic correlation with specific political policy attitudes. This indicates that the Big Five might play a more indirect role in political ideology, perhaps by influencing broader worldview or cognitive style, rather than specific political beliefs.

Furthermore, the study highlighted a significant genetic correlation between right-wing authoritarianism and social dominance orientation themselves, suggesting a common genetic architecture underlies these traits. This is an intriguing finding as it supports the notion that these orientations might not be entirely distinct in their genetic roots, despite differing in their social and psychological manifestations.

Right-wing authoritarianism and social dominance orientation, therefore, appear to form a genetically influenced framework for understanding hierarchy and group dynamics, which in turn shapes individuals political attitudes.

Another notable result is the lack of significant shared environmental effects for most traits, including social dominance orientation and the Big Five personality traits, suggesting that shared family environment and upbringing do not play a major role in developing these ideological orientations. However, a modest shared environmental effect was observed for right-wing authoritarianism, indicating that some aspects of authoritarian attitudes might be influenced by environmental factors common to twins, such as family values or cultural context.

These findings challenge some traditional views in political and social psychology, particularly those that emphasize the role of upbringing and social environment in shaping political ideology. Instead, the results support a more nuanced view that acknowledges a significant genetic component to political attitudes, alongside and sometimes even above personality traits traditionally linked to political orientation.

Our results suggest that the two core ideological traits of [right-wing authoritarianism] and [social dominance orientation] have a much higher (genetic and phenotypic) covariation with political policy attitudes than do Big Five personality traits, the researchers concluded.

The covariation of such ideological traits with policy attitudes is best explained by genetic overlap as opposed to common socialization. These findings challenge key influential theories in social and political psychology and suggest instead that hierarchy-related traits are not simply epiphenomena or downstream consequences of standard personality traits, but instead might form a dedicated and heritable package for navigating intergroup struggles over territory and resources.

But the study, like all research, includes some limitations. For one, it relies on data from a relatively homogeneous population middle-aged adults from Norway which might not represent the global diversity in political attitudes. Future research could expand on these findings by exploring other populations.

The study, The genetic underpinnings of right-wing authoritarianism and social dominance orientation explain political attitudes beyond Big Five personality, was authored by Thomas Haarklau Kleppesto, Nikolai Olavi Czajkowski, Jennifer Sheehy-Skeffington, Olav Vassend, Espen Roysamb, Nikolai Haahjem Eftedal, Jonas R. Kunst, Eivind Ystrom, and Lotte Thomsen.

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Right-wing authoritarianism appears to have a genetic foundation - PsyPost

Genetics

UC Irvine-led research team builds first tandem repeat expansions genetic reference maps – UCI News

Irvine, Calif., April 5, 2024 A research team led by the University of California, Irvine has built the first genetic reference maps for short lengths of DNA repeated multiple times which are known to cause more than 50 lethal human diseases, including amyotrophic lateral sclerosis, Huntingtons disease and multiple cancers.

The UC Irvine Tandem Genome Aggregation Database enables researchers to study how these mutations called tandem repeat expansions are connected to diseases, to better understand health disparities and to improve clinical diagnostics.

The study, published online today in the journal Cell, introduces the UC Irvine TR-gnomAD, which addresses a critical gap in current biobank genome sequencing efforts. Although TR expansions constitute about 6 percent of our genome and substantially contribute to complex congenial conditions, scientific understanding of them remains limited.

This groundbreaking project positions UC Irvine as a leader in human and medical genetics by addressing the critical gap in the ability to interpret TR expansions in individuals with genetic disorders, said Wei Li, the Grace B. Bell Chair and professor of bioinformatics and co-corresponding author. The TR-gnomAD advances our ability to determine how certain diseases might affect diverse groups of people based on variations in these mutations among ancestries. Genetic consulting companies can then develop products to interpret this information and accurately report how certain traits might be linked to different groups of people and diseases.

To build the database, the team utilized two software tools to analyze the genomic data of 338,963 participants across 11 sub-populations. Of the .91 million TRs identified, .86 million were of high enough quality to be retained for further study. It was also discovered that 30.5 percent of them had at least two common alternative forms of a gene caused by a mutation located in the same place on a chromosome.

Although weve successfully genotyped a substantial number of TRs, that is still just a fraction of the total number in the human genome, Li said. Our next steps will be to prioritize the integration of a greater number of high-quality TR and include more underrepresented ancestries, such as Australian, Pacific Islander and Mongolian, as we move closer to realizing personalized precision medicine.

UC Irvine team members involved in the research included co-corresponding author and research assistant professor Ya Cui; Wenbin Ye, postdoctoral scholar; Jason Sheng Li, biological chemistry graduate student; and Eric Vilain, professor of pediatrics and the director of the Institute for Clinical andTranslational Science. Also participating were Jingi Jessica Le, UCLA biostatistics professor, and Dr. Tamer Sallam, vice chair and associate professor at the UCLA David Geffen School of Medicine.

UC Irvines Brilliant Future campaign: Publicly launched on Oct. 4, 2019, the Brilliant Future campaign aims to raise awareness and support for UC Irvine. By engaging 75,000 alumni and garnering $2 billion in philanthropic investment, UC Irvine seeks to reach new heights of excellence instudent success, health and wellness, research and more. The School of Medicine plays a vital role in the success of the campaign. Learn more by visiting https://brilliantfuture.uci.edu/uci-school-of-medicine.

About the University of California, Irvine:Founded in 1965, UC Irvine is a member of the prestigious Association of American Universities and is ranked among the nations top 10 public universities byU.S. News & World Report. The campus has produced five Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UC Irvine has more than 36,000 students and offers 224 degree programs. Its located in one of the worlds safest and most economically vibrant communities and is Orange Countys second-largest employer, contributing $7 billion annually to the local economy and $8 billion statewide.For more on UC Irvine, visitwww.uci.edu.

Media access: Radio programs/stations may, for a fee, use an on-campus ISDN line to interview UC Irvine faculty and experts, subject to availability and university approval. For more UC Irvine news, visit news.uci.edu. Additional resources for journalists may be found at https://news.uci.edu/media-resources.

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UC Irvine-led research team builds first tandem repeat expansions genetic reference maps - UCI News

Genetics

A Deep Dive Into the Genetics of Alcohol Consumption – University of California San Diego

But the paper notes individuals with the alcohol-protective alleles also had worse health outcomes in certain areas: more lifetime tobacco use, more emotional eating, more Graves disease and hyperthyroidism. Individuals with the alcohol-protective alleles also reported totally unexpected differences, such as more malaria, more myopia and several cancers, particularly more skin cancer and lung cancer, and more migraine with aura.

Sanchez-Roige acknowledged that there is a chicken-and-egg aspect to their findings. For example: Cardiovascular disease is just one of a number of maladies known to be associated with alcohol consumption. So is alcohol consumption leading to these conditions? she asks. Palmer finishes the thought: Or do these genetic differences influence traits like malaria and skin cancer in a manner that is independent of alcohol consumption?

Sanchez-Roige said that such broad, hypothesis-free studies are only possible if researchers have access to very large sets of data. Many datasets, including the one used in the study, rely heavily on individuals with European ancestry.

It is important to include individuals from different ancestral backgrounds in genetic studies because it provides a more complete understanding of the genetic basis of alcohol behaviors and other conditions, all of which contributes to a more inclusive and accurate understanding of human health, she said. The study of only one group of genetically similar individuals (for example, individuals of shared European ancestry) could worsen health disparities by aiding discoveries that will disproportionately benefit only that population.

She said their study opens numerous doors for future research, chasing down possible connections between the alcohol-protective alleles and conditions that have no apparent connection with alcohol consumption.

Understanding the underlying mechanisms of these effects could have implications for treatments and preventative medicine, Sanchez-Roige noted.

Co-authors on the paper from the University of California San Diego School of Medicine Department of Psychiatry are Mariela V. Jennings, Natasia S. Courchesne-Krak, Renata B. Cupertino and Sevim B. Bianchi. Sandra Sanchez-Roige is also associated with the Department of Medicine, Division of Genetic Medicine, Vanderbilt University.

Other co-authors are: Jos Jaime Martnez-Magaa, Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine; Laura Vilar-Rib, Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall dHebron Research Institute, Universitat Autnoma de Barcelona, Barcelona, Spain; Alexander S. Hatoum, Department of Psychology & Brain Sciences, Washington University in St. Louis; Elizabeth G. Atkinson, Department of Molecular and Human Genetics, Baylor College of Medicine; Paola Giusti-Rodriguez, Department of Psychiatry, University of Florida College of Medicine; Janitza L. Montalvo-Ortiz, Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine, National Center of Posttraumatic Stress Disorder, VA CT Healthcare Center; Joel Gelernter, VA CT Healthcare Center, Department of Psychiatry, West Haven CT; and Departments of Psychiatry, Genetics & Neuroscience, Yale Univ. School of Medicine; Mara Soler Artigas, Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall dHebron Research Institute, Universitat Autnoma de Barcelona, Barcelona, Spain; Department of Mental Health, Hospital Universitari Vall dHebron, Barcelona; Biomedical Network Research Centre on Mental Health (CIBERSAM), Madrid; and Department of Genetics, Microbiology, and Statistics, Faculty of Biology, Universitat de Barcelona; Howard J. Edenberg, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine; and the 23andMe Inc. Research Team, including Sarah L. Elson and Pierre Fontanillas.

The study was funded, in part, by Tobacco-Related Disease Research Program grants T32IR5226 and 28IR-0070, National Institute of Health (NIH) National Institute of Drug Abuse (NIDA) DP1DA054394, and NIH National Institute of Mental Health (NIMH) R25MH081482.

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A Deep Dive Into the Genetics of Alcohol Consumption - University of California San Diego

Genetics

Untold story of bird evolution revealed through genetics – Earth.com

The cataclysmic impact of a giant meteor around 65 million years ago brought an end to the reign of the majority of dinosaur species, leaving behind a void in which birds, the direct descendants of dinosaurs, emerged as thriving survivors.

This event marks a critical junction in the evolution of birds, which have since exploded into a diverse group of approximately 10,000 species today.

Scientists have long struggled to piece together a comprehensive family tree of birds to understand their evolutionary journey across millennia.

The advent of affordable DNA sequencing technologies promised a resolution to this complex puzzle, simplifying the classification process that has bewildered researchers for centuries, much like it has facilitated the understanding of lineage and relationships across a multitude of other species.

However, the avian world was not without its enigmas. Recent scientific endeavors have found that an event concurrent with the dinosaurs demise 65 million years ago had obscured the true lineage of birds.

This discovery emerged from a pair of groundbreaking research papers released on April 1, which identified a segment of one chromosome that remained in stasis, resisting the natural blending with adjacent DNA regions over the course of millions of years.

This peculiar fragment, representing a mere two percent of the entire bird genome, previously led scientists to believe that the avian family tree could be broadly divided into two major groups, with species such as flamingos and doves considered closely related evolutionary kin.

The discovery of a more precise family tree, which takes into account the deceptive nature of this genome segment, now proposes four primary avian groups and places flamingos and doves in more distant branches of the evolutionary lineage.

My lab has been chipping away at this problem of bird evolution for longer than I want to think about, said senior author Edward Braun, a professor of biology at the University of Florida. We had no idea there would be a big chunk of the genome that behaved unusually. We kind of stumbled onto it.

Decades ago, Braun and his team embarked on a journey to construct a family tree for the Neoaves, which encompasses the majority of existing bird species.

Initial analyses based on the genomes of 48 species led to the classification of the Neoaves into two overarching categories, segregating doves and flamingos into one group, with all other species in the opposing group.

A subsequent analysis involving 363 species, however, produced a divergent family tree that separated doves and flamingos into distinct categories.

Confronted with two conflicting interpretations of the avian family tree, the researchers delved deeper into the genetic data in search of clues that could clarify which version was correct.

When we looked at the individual genes and what tree they supported, all of a sudden it popped out that all the genes that support the older tree, theyre all in one spot. Thats what started the whole thing, Braun explained.

Further investigations revealed that a specific section of the bird chromosome had not undergone the expected genetic mixing through the process of recombination a fundamental mechanism in sexual reproduction that ensures genetic diversity within a species.

This suppression of recombination in a critical genome segment coinciding with the period of dinosaur extinction had caused flamingos and doves to appear more closely related than they truly are when considering the entirety of the genome.

The discovery of this anomalous genomic region, capable of misleading evolutionary analysis yet detectable more than 60 million years later, is a proof of the complexity of bird evolution and the challenges inherent in unraveling the true history of these avian descendants of dinosaurs.

Braun highlighted the potential for similar mysteries to exist within the genomes of other organisms, as yet undiscovered due to the lack of extensive genetic sequencing efforts.

We discovered this misleading region in birds because we put a lot of energy into sequencing birds genomes. I think there are cases like this out there for other species that are just not known right now, Braun concluded.

The study is published in the journal Proceedings of the National Academy of Science.

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Untold story of bird evolution revealed through genetics - Earth.com

Genetics

Scientists Discover 17 New Genetic Variants Linked to Alzheimer’s Disease – SciTechDaily

Recent research has uncovered genetic variants associated with Alzheimers disease risk, using whole genome sequencing to provide new insights into potential treatment pathways. This study highlights the importance of diversity in genetic research and aims to further explore these variants in future studies.

A recent study utilized whole genome sequencing to accurately identify particular genes and genetic alterations within regions previously linked to Alzheimers disease, aiming to guide the development of upcoming treatment and prevention approaches.

Uncovering genetic variants that contribute to the likelihood of developing Alzheimers disease is key to advancing our understanding of how to manage this incurable neurodegenerative disorder. A collaborative study between Boston University School of Public Health (BUSPH) and UTHealth Houston School of Public Health has pinpointed multiple genetic variants that could affect the risk of Alzheimers, moving scientists a step nearer to identifying biological mechanisms that could be targeted in the development of treatments and preventative strategies.

Published in the journal Alzheimers & Dementia: The Journal of the Alzheimers Association, the study utilized whole genome sequencing and identified 17 significant variants associated with Alzheimers disease in five genomic regions. This data enables researchers to pinpoint rare and important genes and variants, building upon genome-wide association studies, which focus only on common variants and regions.

The findings underscore the value of whole genome sequencing data in gaining long-sought insight into the ultimate causes and risk factors for Alzheimers disease, which is the fifth leading cause of death among people 65 and older in the United States. As the most common form of dementia, Alzheimers disease currently affects more than 6 million Americans and that number is expected to skyrocket to nearly 13 million by 2050.

Prior genome-wide association studies using common variants have identified regions of the genome, and sometimes genes, that are associated with Alzheimers disease, says study co-senior author Dr. Anita DeStefano, professor of biostatistics at BUSPH. Whole genome sequence data interrogates every base pair in the human genome and can provide more information about which specific genetic change in a region may be contributing to Alzheimers disease risk or protection.

For the study, the researchers conducted single variant association analyses and rare variant aggregation association tests using whole genome sequencing data from the Alzheimers Disease Sequencing Project (ADSP), a genetics initiative that the National Institutes of Health developed in 2012 as part of the National Alzheimers Project Acts goal to treat and prevent the disease. The ADSP data include more than 95 million variants among 4,567 participants with or without the disease.

Among the 17 significant variants that were linked to Alzheimers disease, the KAT8 variant was one of the most notable, as it was associated with the disease in both the single and rare variant analyses. The researchers also found associations with several rare TREM2 variants.

By using whole genome sequencing in a diverse sample, we were able to not only identify novel genetic variants associated with Alzheimers disease risk in known genetic regions, but also characterize whether the known and novel associations are shared across populations, says study co-lead and corresponding author Dr. Chlo Sarnowski, assistant professor in the Department of Epidemiology at UTHealth Houston School of Public Health.

The ADSP includes ethnically diverse participants, and the population-specific assessments focused on White/European-ancestry, Black/African-American, and Hispanic/Latino subgroups, as well as a multi-population meta-analysis. Historically, Black and Latino populations have been underrepresented in genetic studies of Alzheimers disease despite having a higher prevalence of the disease than other ethnic groups.

Including participants that represent diverse genetic ancestry and diverse environments in terms of social determinants of health is important to understanding the full spectrum of Alzheimers disease risk, as both the prevalence of the disease and the frequencies of genetic variants can differ among populations, says Dr. DeStefano. The sample sizes in the population-specific analyses were small, so the team had limited ability to detect associations, she says, but we replicated known population differences for the APOE gene, which is one of the best-known and strongest risk genes for Alzheimers disease.

In future studies, the researchers hope to examine the population-specific variants they identified in much larger sample sizes, as well as explore how these variants affect biological functioning.

We are currently working on expanding this research to be able to use whole genome sequencing with larger sample sizes in the ADSP to be able to look at the full array of genetic variants, not only within known Alzheimers disease genetic regions, but across the whole genome, says co-senior author Dr. Gina Peloso, associate professor of biostatistics at BUSPH.

Reference: Key variants via the Alzheimers Disease Sequencing Project whole genome sequence data by Yanbing Wang, Chlo Sarnowski, Honghuang Lin, Achilleas N. Pitsillides, Nancy L. Heard-Costa, Seung Hoan Choi, Dongyu Wang, Joshua C. Bis, Elizabeth E. Blue, , Eric Boerwinkle, Philip L. De Jager, Myriam Fornage, Ellen M. Wijsman, Sudha Seshadri, Jose Dupuis, Gina M. Peloso, Anita L. DeStefano and , 21 March 2024, Alzheimers & Dementia. DOI: 10.1002/alz.13705

The study was also co-led by Yanbing Wang while she was a PhD student in biostatistics at BUSPH. It was funded by the National Institute on Aging under Award Numbers U01 AG058589 and U01 AG068221.

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Scientists Discover 17 New Genetic Variants Linked to Alzheimer's Disease - SciTechDaily