Category Archives: Genetics

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

Genetics

World Anthropology Day showcases multifaceted programs | Binghamton News – Binghamton University

Binghamton Universitys Anthropology Department hosted a World Anthropology Day celebration on Feb.15, with 12 archeology and biological anthropology labs in three science buildings showcasing the departments full range of academic offerings.

Featured labs focused on plants (paleoethnobotany), animals (zooarchaeology), remote sensing and historical analysis, skeletal analysis (osteology), forensic anthropology and human genetics, just to name a few. Professors shared their research topics and what opportunities await curious students in the wide world of anthropology.

At the Lab for Anthropometry and Biomarkers, students interested in biology could learn about organismal biology, exosystems and biomarkers in the field of biological anthropology. Associate Professor Katherine Wander led the presentation at her new lab in Science 2.

Examining these patterns of information can further research in identifying biological changes, assessing disease risk and contributing toward advancements in public health. In the fall, Wander will offer a new lab course called Biomarkers: Measurement & Interpretation, which will offer an in-depth understanding of how biomarkers are measured and why we use them.

Biomarkers are the things that are easy to measure that give us that systems-level interpretation, she said.

If students are interested in excavating artifacts and piecing together their place in our shared history, they may be inclined to visit the Public Archaeology Facility (PAF) in Science 1. Peppered throughout the room were artifacts excavated from across the Northeast, from rusted cannon balls from the French and Indian War to stone tools discovered in the Susquehanna River.

Its really cool to dig a hole and find things that people havent touched in either hundreds or thousands of years, said PhD student Kara Jonas.

PAF offers cultural resource management services to clients as well as community-based programs and a lab open to student volunteers.

Something that I really love is working with local communities (on a site), and having their input and their perspective completely change the stories that you can tell and the questions you can ask, Jonas said.

This summer, Maria ODonovan, the director of the Master of Arts in Public Anthropology program, will offer an archeology field school in Broome County, giving students the chance to gain a wide variety of archeological skills and earn 6 credits.

Archeology is that great combination of history and science, ODonovan said. For students who may be on the fence about anthropology, she offered some advice about where to begin: Start with an Intro to Anthropology course, where you can learn a little bit about all of the different four subfields, and then you can gauge whether youre interested in anthropology as a whole, and if you are, where your specific interests lie.

At Professor Rolf Quams paleoanthropology lab, skeletons of animals and skulls of human ancestors were prominently on display. A degree in paleoanthropology can offer students a chance to understand the wonders of human evolution by examining ancient fossils.

I really enjoy learning about human evolution, but theres also the capacity for traveling and digging up dirt, said PhD student and graduate teaching assistant Cai Caccavari, MA 23. There is a lot of biochemistry in the field, and we rely heavily on it for understanding the relationships beyond just looking at the morphology, because just looking at the bones can only get us so far.

Biochemistry is a crucial part of investigating the past and is used in various ways in the study of anthropology. Coupled with human evolution, students can investigate the growth of development of fossils while utilizing other tools such as CT scans.

If you like biochemistry and human evolution, you could go to graduate school, Caccavari said.

Lecturer Lubna Omars Archaeological Analytical Lab is devoted to the study of human-animal interactions through bone remains. Through zooarcheology, students can piece together small pieces of bones to create a vivid picture of the life of various animals.

It is a type of field for people with specific types of skills. You have to be into solving complex puzzles because the bones are fragmented, Omar said.

The work is closely tied to that of archaeologists, since in excavations, many bones are found in ancient garbage pits, she said.

Cultural resources management usually hires zoo archaeologists like me to help them with their work, otherwise they wont understand what happened at the site, she explained.

At the Archaeology Teaching Lab, Assistant Professor Sbastien Lacombe studies people of the past by analyzing their ancient technology. Students in his lab can also examine the social implications and purpose of crafting these technologies and see the variations of culture across different periods of human evolutionary history.

You have anthropology everywhere. Do you want to be a doctor? Biological anthropology. Do you want to work for the parks service? Archaeology, Lacombe said. Its the human dimension that distinguishes us from any other.

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World Anthropology Day showcases multifaceted programs | Binghamton News - Binghamton University

Genetics

An hereditary liver disease cured with the help of gene scissors – EurekAlert

image:

The image depicts human skin stem cells from which new, liver-like cells have been differentiated. The hepatic biomarker APF produced by the differentiated cells is coloured red. The DNA of cell nuclei is displayed in blue.

Credit: University of Helsinki: Jalil, Keskinen et al.

Argininosuccinate lyase deficiency (ASLD), also known as argininosuccinic aciduria, is a disease that has been enriched in the Finnish genetic heritage. In this severe metabolic disease, the body does not process proteins normally, instead resulting in a very dangerous accumulation of argininosuccinic acid and ammonia. Excess ammonia causes disturbances of consciousness, coma and even death.

In Finland, infants are screened for ASLD to determine the disease risk before symptoms develop. The treatment is an extremely strict lifelong diet and, in severe cases, a liver transplant.

Researchers from the University of Helsinki and HUS Helsinki University Hospital have succeeded in correcting the gene defect associated with argininosuccinic aciduria and demonstrated that the harmful metabolism caused by the disease can be cured.

In their recently completed study, they initially modified the skin cells of patients with ASLD into stem cells. Subsequently, the researchers reprogrammed the disease-causing gene defects in the stem cells using the CRISPR-Cas9 technique, known as gene scissors. Finally, the researchers guided the corrected stem cells to differentiate into liver cells to see whether the disease that impairs hepatic function was actually cured and that the fixed cells no longer produced the harmful argininosuccinic acid.

In our study, we demonstrated for the first time that the gene defect causing ASLD can be corrected with gene scissors without any adverse effects visible in the cells. The gene-corrected cells were also metabolically improved, says Docent of Stem Cell Biology Kirmo Wartiovaara, specialist in medical genetics, from the University of Helsinki and HUS.

The study was published in the esteemed American Journal of Human Genetics.

In the study, the researchers used mRNA encapsulated inside lipid nanoparticles to get the gene scissors inside the cultured cells.

This gene mixture we produced is based on the formula of a pharmaceutical product already in use, which may facilitate its clinical use in the future. Our next goal is to cure ASLD in mice, says Doctoral Researcher Timo Keskinen from the University of Helsinki.

The same gene editing technique works on living animals and humans, but we dont yet know how safe it is. This is why the matter has to be investigated first in laboratory animals, Keskinen adds.

There are already more than 7,000 hereditary diseases in the world. Finns, as well as other populations originating in small groups of people, have their own genetic disease variants that are more common in the population than elsewhere in the world. Many of these gene variants of our distant ancestors are such that if a child inherits the same variant from both parents, they may develop a severe disease.

Treatments are available for only a handful of hereditary diseases, and curative therapies are even more rare.

However, a cure could be possible if the gene defect causing the disease is eliminated entirely. Thanks to basic research carried out with the help of gene scissors and other precise gene-editing techniques, permanent fixes are gradually starting to emerge, Wartiovaara says.

The study is part of the doctoral theses of Sami Jalil and Timo Keskinen, supervised at the Biomedicum Stem Cell Center of the Biomedicum Helsinki research institute by Docent Kirmo Wartiovaara and Mervi Hyvnen, DMedSc.

American Journal of Human Genetics

Genetic and functional correction of Argininosuccinate Lyase Deficiency in patient cells using CRISPR Adenine Base Editors

4-Apr-2024

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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An hereditary liver disease cured with the help of gene scissors - EurekAlert

Genetics

Resilience to periodic disturbances and the long-term genetic stability in Acropora coral | Communications Biology – Nature.com

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Resilience to periodic disturbances and the long-term genetic stability in Acropora coral | Communications Biology - Nature.com

Genetics

Rare genetic variants found to have a large impact on obesity risk – Drug Target Review

Researchers have gained a deeper understanding of the neural biology of obesity, which could offer potential drug targets.

A new study has identified rare genetic variants in two genes, BSN and APBA1, that have some of the largest impacts on obesity risk discovered to date. Led by researchers at the Medical Research Council (MRC) Epidemiology Unit and the MRC Metabolic Diseases Unit at the Institute of Metabolic Science, both based at the University of Cambridge, whole exome sequencing of body mass index (BMI) was performed in over 500,000 individuals.

Obesity is a significant public health concern as it is a substantial risk factor for other serious conditions, including cardiovascular disease and type 2 diabetes. However, the genetic reasons for why some individuals are more prone to weight gain are not fully understood. Now, the new study indicates thatBSNandAPBA1play a role in the transmission of signals between brain cells, suggesting that age-related neurodegeneration could affect appetite control.

In the past, research has identified multiple obesity-associated gene variants conferring large effects from childhood, acting through the leptin-melanocortin pathway in the brain. The leptin-melanocortin pathway plays a crucial role in appetite regulation. Although BSNandAPBA1encode proteins found in the brain, they are not currently known to be involved in the leptin-melanocortin pathway. Additionally, unlike the obesity genes previously identified, variants inBSNandAPBA1are not associated with childhood obesity. This led the researchers to believe that they may have discovered a new biological mechanism for obesity. A better understanding of the neural biology of obesity may offer more potential drug targets to treat it in the future.

For the whole exome sequencing, the team used UK Biobank and other data. They discovered that genetic variants in the geneBSN, also named Bassoon, can increase the risk of obesity as much as six times. It was also associated with an increased risk of non-alcoholic fatty liver disease and of type 2 diabetes. The Bassoon gene variants were found to affect one in 6,500 adults, meaning they could affect about 10,000 people in the UK.

The scientists worked closely with AstraZeneca to replicate their findings in existing cohorts, using genetic data from individuals in Pakistan and Mexico. Notably, this enabled the team to apply their findings beyond people of European ancestry.

Dr Giles Yeo, study author based at the MRC Metabolic Diseases Unit, commented: We have identified two genes with variants that have the most profound impact on obesity risk at a population level weve ever seen, but perhaps more importantly, that the variation in Bassoon is linked to adult-onset and not childhood obesity. Thus, these findings give us a new appreciation of the relationship between genetics, neurodevelopment and obesity.

This study is published in Nature Genetics.

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Rare genetic variants found to have a large impact on obesity risk - Drug Target Review

Genetics

INTERACT COALITION FORMED TO ADVANCE PATIENT ACCESS TO GENETIC TESTING FOR HEREDITARY … – PR Newswire

SAN DIEGO, April 3, 2024 /PRNewswire/ -- Leading commercial organizations and patient advocacy groups in the field of cancer genetics today announced the founding of the Inter-Organization Cancer Genetics Clinical Evidence Coalition (INTERACT), a coalition whose mission is to increase evidence-based access to genetic testing for people with or at risk of hereditary cancers.

Founding laboratory members include organizer Ambry Genetics, a subsidiary of REALM IDx, Illumina, Myriad Genetics, and Quest Diagnostics. Volpara Health has also recently joined the coalition. Founding patient advocacy organization members include AliveAndKickn and FORCE. The coalition seeks to provide a collective voice in support of the progression of medical professional and industry guidelines for genetic testing for inherited mutations that increase cancer risk.

With growing insight into the role of genetic testing in cancer risk management and treatment, the population of individuals who benefit from knowing their genetic mutation status continues to increase. As leaders in the genetic testing and hereditary cancer field, the founding members believe it is their responsibility to help drive awareness and inform changes that will equalize access for those whose outcomes could benefit most from testing.

One of the primary objectives of INTERACT is to ensure policy and guidelines keep pace with the growing body of evidence surrounding inherited cancer risk.

Hereditary cancer genetic testing has been shown to improve outcomes by identifying those most at risk and informing management strategies. For instance, patients who test positive for a BRCA1 or BRCA2 mutation have up to 87% lifetime risk for breast cancer, and up to 40% lifetime risk for ovarian cancer.1,2 In addition, there are numerous other genes that increase risk for various forms of cancer. Armed with this information, patients and physicians can improve management through increased surveillance, chemoprevention, targeted therapeutics or risk-reducing surgical measures. As an example, studies have shown that prophylactic mastectomy in BRCA1/2 mutation carriers results in up to a 97% reduction in the risk for contralateral breast cancer, while salpingo-oophorectomy reduced ovarian cancer incidence by 69-100%.1,2

Despite the benefits of a patient and their provider knowing mutation status, disparities in access and uptake of cancer genetics services are well documented.3 INTERACT intends to improve access to genetic testing, with the goal of reaching vulnerable populations who may not currently be aware of their risk or their need for increased screening or other interventions.

"With Lynch syndrome, one of the most common hereditary cancer syndromes, patients have up to 80% lifetime risk for colorectal cancer4, but an estimated 95% of at-risk individuals have not been identified5," said Robin Dubin, Executive Director of AliveAndKickn. "To really improve survival rates with informed screening strategies, we need to help drive education and policies that support genetic testing for all those at risk."

Among the challenges to broadening access to genetic testing for hereditary cancer risk is a time lag in updating guidelines and medical policies after the publication of new medical literature. INTERACT will work to bring these differences to the attention of guideline committees and medical professional societies in an effort to bridge the gaps and reduce disparities in access to appropriate testing nationwide.

About INTERACT The mission of INTERACT is to bring together specialized genetic testing laboratories and patient advocacy groups to support the progression and evolution of medical policy and industry guidelines for cancer genetic testing. Our members are recognized institutions in the field of cancer genetics. Current commercial members include Ambry Genetics, a subsidiary of REALM IDx, Illumina, Myriad Genetics, Quest Diagnostics, and Volpara Health. Advocacy members include AliveAndKickn and FORCE: Facing Our Risk of Cancer Empowered. We seek to develop the evidence base and rationale to inform changes in cancer-related genetic testing policies to expand patient access to evidence-based testing.

For more information, visit: https://interactcoalition.org/

References:

Contact: [emailprotected]

SOURCE INTERACT Coalition

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INTERACT COALITION FORMED TO ADVANCE PATIENT ACCESS TO GENETIC TESTING FOR HEREDITARY ... - PR Newswire

Genetics

Christensen Genetics – AG INFORMATION NETWORK OF THE WEST – AGInfo Ag Information Network

Seth Christiansen of Christianson Genetics of Westin, Idaho, explained to me why winter is busier than summer for his operation. Today, our work centers on embryo transfer, and during the winter specifically would be when we do most of that. So during the summer, it's relatively empty Here. The cattle are out grazing during the normal growing season. That would be when they're out on pasture as opposed to being here in the dry lot through that whole winter feeding period. This would be the time when on a normal farm they wouldn't be doing nearly as much just because it's not the growing season. But while everything's frozen, that would be when we are synchronizing the cows, giving them a series of injections to bring them in to heat at the same time, and then doing embryo transfer on those cattle. So pulling embryos out of their very best 5% of the herd and transferring those embryos into the other 95% of the herd, there's about 400 animals total here. Only 20 of those are actually the mothers to the upcoming calf crop. They produce the embryos that are carried by the other cows. And as we implant all those embryos through the winter, the cows that conceive early, so conceive in that December, January time frame to carry one of those embryo transfer pregnancies, We'll keep those as part of the herd and we'll calve those cattle and raise those embryo transfer calves, the cows that conceive later on in the cycle. It's late for us, but it's right on time for most everybody else. If they conceive in March or April, they're going to have a January or February calf, which is when most seed stock operations prefer to calve by bringing in these cattle, doing all this extra work through the winter, we're able to add a lot of value to these animals. The average animal is going to come in to the program as an open female worth 1002 to $500 once we've done all of our winners were and added those embryos to those cows, confirmed those pregnancies through the winter, the average female there is going to be worth between$5000 and $6000.

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Christensen Genetics - AG INFORMATION NETWORK OF THE WEST - AGInfo Ag Information Network

Genetics

New form of EDS identified by mutation in THBS2 gene – Ehlers-Danlos News

A mutation in the gene THBS2 cause a newly defined form of Ehlers-Danlos syndrome (EDS) thats characterized by unusual flexibility as well as prolonged bleeding and blood vessel abnormalities, a new study reports.

The study, Heterozygous THBS2 pathogenic variant causes EhlersDanlos syndrome with prominent vascular features in humans and mice, was published in the European Journal of Human Genetics.

EDS refers to a group of connective tissue disorders that are typically characterized by symptoms including an abnormal range of joint motion and fragile skin. More than a dozen identified types of EDS exist, however, each with different causes and typical manifestations.

The patient at the center of this study is a woman in her late 20s of Ashkenazi Jewish ancestry who sought medical attention for a history of frequent joint dislocations, tendon rupture, easy bruising, and prolonged bleeding when injured. She also reported fatigue in her legs after exercising.

The patients older sister and their mother reported similar symptoms. Imaging studies showed blood vessel abnormalities: the younger sister and her mother both had unusual pooling of blood in veins in the lower legs; the mother also had abnormalities in a heart valve. Of note, the mothers father, who had a history of aneurysms (bulging or swollen blood vessels) while alive, had died of a blood vessel rupture.

The three women underwent EDS-specific genetic testing, but analyses of more than a dozen genes linked to EDS showed no noteworthy findings. A more widespread analysis identified 43 genetic variants that were in both sisters. Most of these were common in people of Ashkenazi Jewish ancestry and were ruled out, and a few others were ruled out by genetic testing of the extended family.

The researchers then zeroed in on a mutation in the THBS2 gene that was found in both sisters, but not their unaffected relatives or in databases of genetic samples from more than 7,000 Ashkenazi Jews.

Everyone inherits two copies of the THBS2 gene, one from each biological parent. In the sisters, just one copy of the gene carried a mutation (called p.Cys896Arg), indicating that this form of EDS is inherited in an autosomal dominant pattern where one mutated copy is sufficient to cause disease.

Our findings demonstrate that the THBS2 p.Cys896Arg variant has a dominant effect, the researchers wrote.

To confirm that this mutation was disease-causing, the researchers generated mice carrying the same mutation in the mouse version of the THBS2 gene. These mice demonstrated excessive flexibility in fact, the researchers said they were able to tie the mices tails into knots without causing the animals any notable distress. The mice also bled excessively when injured.

Upon lab evaluation of the mices tissue, the researchers noted that collagen fibers were disorganized. Collagen is the main protein that gives body tissue its structural integrity, and collagen abnormalities are a defining feature of EDS.

Altogether, these data define a new form of EDS caused by a mutation in the THBS2 gene. The scientists are working on further studies to understand the biological mechanisms of how THBS2 mutations lead to connective tissue abnormalities.

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New form of EDS identified by mutation in THBS2 gene - Ehlers-Danlos News

Genetics

Genetics of estrogen production linked to endometrial cancer risk in postmenopausal women – News-Medical.Net

In a recent study published in eBioMedicine, researchers determine the genetic regulation of blood estrone levels in postmenopausal women to explore associations between their genetic loci and endometrial cancer.

Study:Genome-wide association study identifies genetic regulation of oestrone concentrations and association with endometrial cancer risk in postmenopausal women. Image Credit: Peakstock / Shutterstock.com

Once a woman has gone through menopause, her ovaries no longer produce estrogens, thereby causing her serum estradiol concentrations to be extremely low or undetectable. In Type 1 estrogen-sensitive endometrial cancer, which accounts for over 80% of all endometrial cancers and predominantly affects menopausal women, estrone, the contributing estrogen, is synthesized in non-ovarian tissues like fat. Following the production of estronein these tissues, this hormone is converted into estradiol, a more potent form of estrogen.

Previous studies have shown that obesity is a significant risk factor for Type 1 endometrial cancer. This association may be attributed to the greater amount of total fat mass that facilitates more estrone production.

Alternatively, various genetic factors may lead to increased estrone production after menopause, thereby contributing to an increased risk of endometrial cancer in these women. In fact, one variant in the CYP19A1 gene, which is involved in the aromatization of testosterone to estradiol, has been positively associated with estradiol concentrations and postmenopausal endometrial cancer.

Importantly, studies investigating the relationship between CYP19A1 variants and endometrial cancer risk have been limited due to their small sample size and lack of sensitive analytical methods.

In the present genome-wide association study (GWAS), researchers quantified blood estrone, testosterone, and dehydroepiandrosterone (DHEA) levels with high precision using liquid chromatography-tandem mass spectrometry (LCMS) to identify single nucleotide polymorphisms (SNPs) associated with sex hormone concentrations. The association between hormone-associated SNPs and endometrial cancer was determined from 205,427 white British females between 39 and 71 years of age, 0.9% of whom were diagnosed with endometrial cancer.

The study also included women 70 and older from the Sex Hormones in Older Women (SHOW) and ASPirin in Reducing Events in the Elderly (ASPREE) studies. Non-fasting blood samples were obtained from these study participants to measure sex hormone concentrations through LCMS.

The final analysis cohort comprised 4,951 postmenopausal women of European descent, with a median age of 73.9. No genome-wide signals were observed for testosterone or DHEA, the latter of which is the precursor for both estrone and testosterone. However, the GWAS identified four independent SNPs for estrone concentrations below the genome-wide significance threshold after adjusting for age and BMI.

These SNPs included rs34670419, which may be involved in transcriptional regulation; rs56400819, which contributes to the DNA damage response; rs2846729, which is mapped to a ribonucleic acid (RNA) gene; and rs2414098, which is mapped to CYP19A1. The SNP with the highest prevalence within this study cohort was rs56400819 at 45% as compared to rs34670419, which had the lowest prevalence in this cohort at 4%.

Lower estrone levels were observed for rs34670419, rs2846729, and rs2414098 carriers compared to rs56400819 carriers, who exhibited higher estrone concentrations. Furthermore, rs2414098 carriers had a significantly lower risk of endometrial cancer after adjusting for age at recruitment, BMI, parity, and history of diabetes.

Previous GWAS on endometrial cancer have primarily focused on estradiol concentrations; however, this hormone often cannot be accurately quantified, particularly among postmenopausal women. Comparatively, the current study examined estrone concentrations, in which a dose-response relationship was observed between the identified SNPs and estrone concentrations.

Importantly, the researchers of the current study limited one of their analyses on rs2414098 to women over 58 years of age in an effort to ensure postmenopausal status. These findings confirm that the impact of this SNP on cancer risk can be attributed to estrone and is independent of the effects of circulating estrogens and progesterone.

The current study highlights the importance of measuring estrone levels, in addition to other sex hormones, in postmenopausal women to determine cancer risk. Some important strengths of this study include the confirmation of postmenopausal women in the study cohort, the large sample size, and the use of LCMS, a highly sensitive and precise analytical instrument.

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Genetics of estrogen production linked to endometrial cancer risk in postmenopausal women - News-Medical.Net

Genetics

Cord Blood Registry (CBR) by CooperSurgical and Fulgent Genetics Launch Innovative Genetic Testing – PR Newswire

Testing offers CBR families the opportunity to proactively seek additional information about their child's health

TRUMBULL, Conn. and EL MONTE, Calif., Feb. 9, 2024 /PRNewswire/ -- CooperSurgical, a global leader in fertility and women's health, and Fulgent Genetics, Inc. (NASDAQ: FLGT), a technology-based company with a well-established clinical diagnostic business and a therapeutic development business, today announced that they have partnered to offer families of Cord Blood Registry (CBR) exclusive newborn genetic screening panels.

"We are proud to offer our CBR families additional resources that complement our newborn stem cell services as we continue to deliver personalized, cutting-edge solutions to families nationwide," said Holly Sheffield, President of CooperSurgical.

Utilizing Fulgent's Picture Genetics platform, CBR, the largest private newborn stem cell preservation company in the world, now offers a range of genetic testing options to its families, including:

"Partnering with CBR allows us to help provide more families with actionable information about their newborn's health," said Brandon Perthuis, Chief Commercial Officer of Fulgent Genetics. "Part of our mission is to use our resources and testing to improve the lives of those around us. Newborn genetic analysis serves as an illustration of this commitment, as early intervention may significantly improve health outcomes for many of these conditions."

These Picture Genetic tests are available now exclusively to CBR clients. All three Picture tests evaluate over 30 genes associated with conditions that are potentially treatable with newborn stem cells as part of a stem cell transplant.1

For more information, please visit http://www.cordblood.com/genetic-testing.

About CBRby CooperSurgical

Cord Blood Registry (CBR) is the largest private newborn stem cell company in the world, helping parents store stem cells from cord blood and cord tissue for their children. Founded in 1994, CBR is the #1 choice for parents1 and most recommended by OB/GYNs for newborn stem cell preservation.2 The company has released over 700 samples intended for use in transplant medicine and regulated investigational regenerative medicine applications.1 CBR is here to help expand the possibilities of what newborn stem cell therapies can do for families and give parents the confidence to Bank on CBR. More information can be found at http://www.cordblood.com.

About CooperSurgical

CooperSurgical is a leading fertility and women's healthcare company dedicated to putting time on the side of women, babies, and families at the healthcare moments that matter most in life. CooperSurgical is at the forefront of delivering innovative assisted reproductive technology and genomic solutions that enhance the work of ART professionals to the benefit of families. We currently offer over 600 clinically relevant medical devices to women's healthcare providers, including testing and treatment options.

CooperSurgical is a wholly-owned subsidiary of CooperCompanies (Nasdaq:COO). CooperSurgical, headquartered inTrumbull, CT, produces and markets a wide array of products and services for use by women's health care clinicians. More information can be found atwww.coopersurgical.com.

About CooperCompanies

CooperCompanies (Nasdaq: COO) is a leading global medical device company focused on improving lives one person at a time. The Company operates through two business units, CooperVision and CooperSurgical. CooperVision is a trusted leader in the contact lens industry, improving the vision of millions of people every day. CooperSurgical is a leading fertility and women's health company dedicated to assisting women, babies, and families at the healthcare moments that matter most. Headquartered in San Ramon, CA, CooperCompanies ("Cooper") has a workforce of more than 15,000 with products sold in over 130 countries. For more information, please visitwww.coopercos.com.

About Picture Genetics

Picture Genetics was launched in 2019 as a service of Fulgent Genetics. Picture Genetics offers consumers direct access to Fulgent's advanced genetic testing and analytics capabilities from the ease and comfort of home, at an affordable price point. With multiple tests available to meet the varying needs of consumers, Picture Genetics provides a holistic approach to at-home genetic screening to complement Fulgent's comprehensive genetic testing analysis. Picture Genetics reports provide medically actionable, clinical-level results with professional medical oversight in one easy process. Visit http://www.picturegenetics.comfor more information.

About Fulgent

Fulgent is a technology-based company with a well-established clinical diagnostic business and a therapeutic development business. Fulgent's clinical diagnostic business offers molecular diagnostic testing services, comprehensive genetic testing, and high-quality anatomic pathology laboratory services designed to provide physicians and patients with clinically actionable diagnostic information to improve the quality of patient care. Fulgent's therapeutic development business is focused on developing drug candidates for treating a broad range of cancers using a novel nanoencapsulation and targeted therapy platform designed to improve the therapeutic window and pharmacokinetic profile of new and existing cancer drugs. The company aims to transform from a genomic diagnostic business into a fully integrated precision medicine company.

References

Contact CooperSurgical EvolveMKD [emailprotected]

Fulgent GeneticsMelanieSoloman, The Blueshirt Group [emailprotected]

SOURCE CooperSurgical

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Cord Blood Registry (CBR) by CooperSurgical and Fulgent Genetics Launch Innovative Genetic Testing - PR Newswire