Category Archives: Genetics

Genetics

Seedling root system adaptation to water availability during maize domestication and global expansion – Nature.com

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Seedling root system adaptation to water availability during maize domestication and global expansion - Nature.com

Genetics

Class of 2024: After completing the human genetics certificate program, Alanna Varca Gentile is translating personal … – VCU News

By Grace McOmber School of Medicine

Medicine had been the plan since high school for Alanna Varca Gentile. Motivated by her own experiences as a patient, she enrolled at Virginia Commonwealth University in VCU Acceleration, a program for incoming freshmen interested in health care, and confidently began the pre-medical track.

But when the COVID-19 pandemic hit during Varca Gentiles junior year, she began questioning whether medical school was the right fit.

I really enjoyed my time in the Acceleration program, Varca Gentile said. But I think the pandemic really made me start to ask a lot of questions about what I really wanted and what I was mentally prepared for.

Still interested in medicine but unsure of her plan, Varca Gentile said she confided in a professor only days before graduating with her bachelors degree in psychology from the College of Humanities and Sciences in 2021. The professor suggested genetic counseling a field shed never heard of.

I didnt even know what clinical genetic counseling was before that, Varca Gentile said. I went on an internet deep dive and attended phone call informational interviews. I had a really good gut feeling about this path.

In 2023, she enrolled in the Certificate in Clinical Genetics program, one of five certificate programs offered by the VCU School of Medicine to enhance students qualifications for advanced degrees, continued education and highly specialized fields. Varca Gentile said the academic exposure and networking opportunities solidified her interest in the niche, competitive field and helped her get into the genetic counseling M.S. program at VCU, which shell begin in the fall. Many of her credits from the certificate program will count toward her masters.

She also received the Genetic Counseling Equity Scholarship, which is awarded to a qualified applicant who demonstrates a commitment to serving populations that are historically underprivileged or underserved by the field of genetic counseling.

Im hoping to get involved in outreach for genetic counseling, Varca Gentile said. I want to help bring more diversity to the field, mentor students from underrepresented backgrounds and work towards making the field a more accessible service to patients.

Genetic counseling, according to the National Society of Genetic Counselors, is a relatively young field at a little over 50 years old. The practice combines the scientific analysis of human genetics with patient consultations. Counselors assess patients risk for inherited diseases, educate families about genetic disorders like sickle cell and Huntingtons and present options on how to adapt to findings. This combination of science and psychosocial work was what attracted Varca Gentile to the field.

It's a very empathy-heavy role, Varca Gentile said. Youre taking the time, establishing a relationship and walking patients through some really scary topics.

As she prepares to become a genetic counselor, Varca Gentile draws on her own experiences as a patient. A concussion during high school caused a traumatic brain injury with long-lasting effects she still deals with today. Despite following typical concussion protocols, she has experienced regular headaches and migraines since the injury. She also developed postural orthostatic tachycardia syndrome, which is also known as POTS, from the injury, which affects the autonomic nervous system, causing heart rate and blood pressure dysregulation and resulting in dizziness, light-headedness and heart palpitations.

My brain processes very differently than it did before my TBI, Varca Gentile said, noting that the chronic pain impacts her capabilities as a student, and shes grateful for the disability services and accommodations through the Division of Student Affairs and Division for Academic Success. POTS is sort of a daily struggle, and it adds a lot of fatigue and brain fog to my life.

Over the past nine years, Varca Gentiles interactions with medical professionals have been mixed, inspiring her to be a counselor who leads with empathy and advocates for her patients. Her POTS and vertigo diagnoses came after a long string of appointments with different specialists, which she said gives her a unique perspective on the diagnostic odyssey many patients go through. When the headaches became a nearly daily occurrence, she said it took longer than it should have to be referred to a neurologist, which made her feel unheard by her doctor.

A lot of people are dismissive of pain and struggle, especially when it comes to young women, Varca Gentile said. Im excited to be a female provider and be a voice for my patients, especially for people who often go dismissed.

Varca Gentiles empathy doesnt stop with her future patients. After graduate school, she hopes to work at a university-affiliated hospital, such as VCU Health, to pay forward the support she received during the certificate program. The Association of Genetic Counseling Program Directors reports that only 59% of applicants matched into genetic counseling M.S. programs in 2024, making it one of the most competitive fields in health care.

I know how hard getting into genetic counseling school is, and I want to help in the way people helped me, Varca Gentile said. Its a small field, but its a great community.

Heather Creswick, the clinical genetics certificate advisor, said the genetic counseling faculty is excited to have Varca Gentile join the program in the fall. Creswick described her as a driven, curious hard worker who connects well with those around her.

I hope Alanna finds joy in engaging with her patients and that she is surrounded by colleagues who inspire and guide her, Creswick said. I hope that she will embrace learning, stay open-minded and get involved with the profession. She has great potential to be a leader in this field.

For now, Varca Gentile said she is excited to become a four-time Ram and continue her education at VCU, learning under many of the same instructors she did during her certificate program.

I made great connections during the program that I am so incredibly grateful for, Varca Gentile said. I wouldnt have gotten in without them.

This article was originally published on the VCU School of Medicines website.

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Class of 2024: After completing the human genetics certificate program, Alanna Varca Gentile is translating personal ... - VCU News

Genetics

Sequencing of the developing human brain uncovers hundreds of thousands of new gene transcripts – UCLA Newsroom

Key takeaways

A team led by researchers at UCLA and the University of Pennsylvania has produced a first-of-its kind catalog of gene-isoform variation in the developing human brain. This novel dataset provides crucial insights into the molecular basis of neurodevelopmental and psychiatric brain disorders and paves the way for targeted therapies.

The research, published in Science, also details how transcript expression varies by cell type and maturity, finding that changing gene-isoform expression levels can help us better understand how the human brain develops.

Every cell in our body contains the same genetic information encoded in DNA, but it is the expression of different proteins, encoded in mRNA transcripts, that give cells their distinct functions. These varied proteins, or isoforms, mostly arise from alternative splicing a process that is highly prevalent in the brain and contributes to its wide range of proteins and characteristics.

We knew, based on our previous research, that isoform regulation is a key molecular feature for understanding brain development and genetic risk for neuropsychiatric disorders, said Dr. Luis de la Torre-Ubieta of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, who co-led the study alongside Dr. Michael Gandal, an associate professor of psychiatry and genetics in the Perelman School of Medicine at the University of Pennsylvania.

Previously, despite its prevalence, the role of cell-type-specific splicing and transcript-isoform diversity in the developing human brain had not been systematically investigated due to limitations in prior generations of sequencing technologies. Here, the researchers were able to leverage new third-generation long-read sequencing technologies to capture complete RNA molecules and profile the full-length transcriptome of two major regions of the developing neocortex: the germinal zone, which contains stem cells, and the cortical plate, which houses newly generated neurons.

This technology allowed the researchers to uncover 214,516 unique isoforms over 70% of which have never been previously studied. They then compared the two regions of the developing brain and observed that changes in isoform expression levels are important for neurogenesis, differentiation and cell fate in essence, the maturation of the brain.

The researchers found thousands of isoform switches that occur during brain development, implicating previously uncharacterized RNA-binding proteins in cellular identity and cellular fate decisions. Their findings also elucidate genetic risk mechanisms for neurodevelopmental and neuropsychiatric disorders, including a reassessment of the significance and clinical relevance of thousands of rare genetic variants.

We found that high-confidence risk genes for autism or neurodevelopmental disorders tend to be genes that have more isoforms, and those isoforms are expressed differently during neurogenesis, said de la Torre-Ubieta, an assistant professor of psychiatry and behavioral sciences. This implies that dysregulation of the expression of specific isoforms is a potential mechanism underlying these disorders.

Scientists studying the brain often rely on publicly available catalogs of genes and gene transcripts. However, human brain tissue, particularly embryonic tissue, is difficult to access, restricting the comprehensiveness of these datasets. For this study, the researchers obtained six developing human neocortex tissue samples representing the mid-gestation period, or 15 to 17 weeks post-conception. This developmental time point in the human brain is a critical window during which the complexity of our brain the most sophisticated organ in our body begins to emerge.

These tissue samples enabled a striking level of novel transcript discovery, Gandal said. And because these databases havent incorporated or represented these critical time points, we can dramatically expand our understanding of how genes are regulated in the context of human brain development.

The findings from the study have strong therapeutic implications and could be clinically actionable, the researchers said. Uncovering new transcripts could pave the way for identifying novel treatment approaches in gene therapy trials or targeted therapeutic trials for individuals harboring rare mutations associated with psychiatric or neurodevelopmental disorders.

In the nearer term, the data also has direct implications in improving our ability to make genetic diagnoses of neurodevelopmental disorders. Because the study found several thousand genetic variants that are more impactful than previously thought, families or individuals carrying those variants can better understand how their children might be predisposed to certain disorders.

Gandal has shared the dataset with several colleagues at the Childrens Hospital of Philadelphia, which has a large population of children with rare neurodevelopmental disorders or undiagnosed disorders in development. Physicians there are already using this resource to help better interpret neurogenetics diagnostically.

Im really excited to leverage this resource to help patients, said Gandal, who is also a practicing psychiatrist. Having this knowledge brings us one step closer to being able to develop targeted treatments and understand genetic mechanisms in a much more specific way.

Other UCLA authors include Ashok Patowary, Pan Zhang, Celine K. Vuong, Xinzhou Ge, Kangcheng Hou, Minsoo Kim, Michael Margolis, Bogdan Pasaniuc and Jingyi Jessica Li. Connor Jops, Naihua Gong, Daniel Vo, Xusheng Wang and Chunyu Liu contributed to this study.

The research was supported by the Simons Foundation Autism Research Initiative, the National Institute of Mental Health, the National Science Foundation and the UCLA Medical Scientist Training Program.

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Sequencing of the developing human brain uncovers hundreds of thousands of new gene transcripts - UCLA Newsroom

Genetics

Myriad Genetics Showcases New Research and Product Innovations Advancing Cancer Care at 2024 ASCO Annual … – GlobeNewswire

SALT LAKE CITY, May 23, 2024 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc., (NASDAQ: MYGN), a leader in genetic testing and precision medicine, and its collaborators will share data from seven studies at the 2024 ASCO Annual Meeting. Three studies led by Myriad focus on breast cancer risk assessment, and four additional studies will be shared by collaborators that will cover the companys Precise MRD Test, MyChoice CDx HRD Companion Diagnostic Test, and the Myriad Collaborative Research Registry (MCRR). At booth 25014, Myriad will highlight the value of genetic testing and genomic insights in guiding personalized cancer treatment decisions, as well as share information about upcoming product innovations including MRD and liquid biopsy testing.

New Data at ASCO

Oral Presentation: Evaluation of a polygenic risk score as a predictor of early onset triple-negative breast cancer in Black women (Abstract #: 10501) Presenter: Holly J. Pederson, MD, Director, Medical Breast Services, Cleveland Clinic Date: Saturday, June 1, 2024 Time: 3:12 pm CT Description: This study demonstrates that Myriads RiskScore improves upon clinical factors for the prediction of triple-negative breast cancer and early onset (<50 years) triple-negative breast cancer in Black women.

Poster: Comparison of primary versus metastatic tumor tissue sources when designing panels for whole-genome-based tumor-informed ctDNA assays in clear cell renal cell carcinoma (Abstract #3039) Date: Saturday, June 1, 2024 Time: 9:00am 12:00pm CT Description: In a pilot study of patients with oligometastatic renal cell carcinoma, molecular residual disease (MRD) results were largely concordant with mortality status and between monitoring panels composed of thousands of probes identified from either primary or metastatic tumors, suggesting repeat biopsy might not be necessary for long term MRD monitoring.

Poster: Improving a polygenic risk score (PRS) for breast cancer (BC) risk assessment in diverse ancestries(Abstract #: 10533) Date: Monday, June 3, 2024 Time: 1:30 4:30pm CT Description: This study highlights a new 385-SNP PRS component of RiskScore and demonstrates it is well-calibrated, improves upon clinical factors, and outperformed existing PRS in all tested ancestries for the prediction of breast cancer risk.

Poster: Association of polygenic-based breast cancer risk prediction with patient management(Abstract #: 10527) Date: Monday, June 3, 2024 Time: 1:30 4:30pm CT Description: The study demonstrates that clinicians recommended breast cancer screening aligned with guidelines for those with 20% lifetime risk, regardless of whether risk was based on RiskScore or on Tyrer-Cuzick alone.

Poster: Germline Genetic Profiles of Women with Ovarian Malignancies: A Myriad Collaborative Research Registry Study (Abstract #: 5585) Date: Monday, June 3, 2024 Time: 9:00 am 12:00pm CT Description: This data shows that over 15% of patients with ovarian cancer have BRCA1/2 (12.5%) or Lynch syndrome (2.6%) pathogenetic variants varying by race, age, and tumor site. Noted disparities indicate the importance of universal testing in patients with ovarian cancer.

Poster: Germline Genetic Profiles of Women with Uterine Cancer: A Myriad Collaborative Research Registry Study(Abstract #: 5617) Date: Monday, June 3, 2024 Time: 9:00 am 12:00pm CT Description: There are significant differences in germline testing results for women with uterine cancer by race, ethnicity, and age, especially in genes associated with Lynch syndrome. This has implications for immunotherapy eligibility in the advanced and recurrent setting. More work needs to be done to identify targetable mutations in minority populations.

Poster: Neoadjuvant combination treatment of olaparib and pembrolizumab for patients with HRD-positive advanced ovarian cancer (Abstract #: 5545) Date: Monday, June 3, 2024 Time: 9:00 am 12:00pm CT Description: This study shows that neoadjuvant combination therapy of olaparib and pembrolizumab is effective and tolerable in patients with HRD-positive advanced ovarian cancer. BRCA1/2 mutations are associated with the efficacy of combination therapy.

Myriad Oncology Innovations Myriad continues to expand its oncology portfolio and expertise through product innovations and the addition of new team members, including the appointment of George Daneker Jr., MD, who is the president and chief clinical officer of oncology. Myriads Precise Oncology Solutions portfolio features comprehensive germline and somatic testing options, including the MyRisk Hereditary Cancer Test with RiskScore, Precise Tumor Test, Prolaris Prostate Cancer Prognostic Test, EndoPredict Breast Cancer Prognostic Test, Folate Receptor Alpha (Fr) Test, and Myriads two FDA-approved companion diagnostic tests: MyChoice CDx HRD Companion Diagnostic Test and BRACAnalysis CDx Germline Companion Diagnostic Test.

Ongoing oncology developments include:

MRD research collaborations. In the past year, Myriad has announced several important research collaborations: a retrospective study of MRD efficacy in metastatic breast cancer with researchers at Memorial Sloan Kettering Cancer Center (MSK), a retrospective analysis of MRD utility in metastatic renal cell carcinoma with clinicians at The University of Texas MD Anderson Cancer Center, and a prospective pan-cancer study with MRD researchers at the National Cancer Center Hospital East in Japan. Early results from the research collaboration with MD Anderson will be shared at ASCO as a poster.

As we continue to innovate and grow our oncology business, our vision remains centered around advancing oncology care for all patients, said Dr. Daneker. Our new research and product innovations underscore our commitment to partnering with oncologists, academic institutions and other healthcare partners to expand access to genetic and genomic testing, create equitable testing solutions for all, and provide data-driven insights that can better inform clinical care and improve outcomes for patients.

About Myriad Genetics Myriad Genetics is a leading genetic testing and precision medicine company dedicated to advancing health and well-being for all. Myriad develops and offers genetic tests that help assess the risk of developing disease or disease progression and guide treatment decisions across medical specialties where genetic insights can significantly improve patient care and lower healthcare costs. For more information, visit http://www.myriad.com.

Safe Harbor Statement This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the data and information that the company plans to present at the 2024 ASCO Annual Meeting and updates on upcoming product innovations including MRD and liquid biopsy testing. These forward-looking statements are managements expectations of future events as of the date hereof and are subject to known and unknown risks and uncertainties that could cause actual results, conditions, and events to differ materially and adversely from those anticipated. Such factors include those risks described in the companys filings with the U.S. Securities and Exchange Commission, including the companys Annual Report on Form 10-K filed on February 28, 2024, as well as any updates to those risk factors filed from time to time in the companys Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. Myriad is not under any obligation, and it expressly disclaims any obligation, to update or alter any forward-looking statements, whether as a result of new information, future events or otherwise except as required by law.

Investor Contact Matt Scalo (801) 584-3532 IR@myriad.com

Media Contact Glenn Farrell (385) 318-3718 PR@myriad.com

Continued here:
Myriad Genetics Showcases New Research and Product Innovations Advancing Cancer Care at 2024 ASCO Annual ... - GlobeNewswire

Genetics

Ambry Genetics and PacBio Announce Collaboration To Sequence up to 7000 Human Genomes – Technology Networks

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Ambry Genetics, along with PacBio (NASDAQ: PACB), announced their companies selection by the University of California, Irvine (UCI) and the GREGoR Consortium (Genomics Research to Elucidate the Genetics of Rare diseases) to support the Pediatric Mendelian Genomics Research Center (MGRC) program to better understand the underlying biology of rare diseases.

The GREGoR Consortium is a National Institutes of Health-funded collaborative effort which aims to transform the landscape of Mendelian disease research by identifying the underlying genetic cause of rare disease in samples from individuals for whom prior genomic analysis did not yield answers. This ambitious research, among the largest programs of its kind, will use long-read sequencing technology to sequence and analyze up to 7,000 human whole genomes over three years, with a focus on developing new insights into rare disease etiology.

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This pioneering initiative unites leading genomics researchers who will work collaboratively to incorporate innovative methods for understanding the biology of rare disease including phenotyping, variant identification, and functional analysis of both coding and non-coding sequence alterations. By using highly accurate 5-base, long-read sequencing technology, the researchers hope to discover new rare variants and to understand the role of epigenomics on disease manifestation. By building new analysis pipelines for these genomic and epigenomic data, the researchers hope to discover new Mendelian gene variations and to better categorize previously identified variants of unknown significance.

Over the past few years, weve collaborated with leading genomics researchers around the world to advance the scientific communitys understanding of the genomic basis of rare disease, said Christian Henry, President and Chief Executive Officer of PacBio. This project with the GREGoR team represents a significant step forward for us. We hope that by partnering with scientists at U.C. Irvine and geneticists from Ambry Genetics, we will not only be able to help families better understand the underlying causes of rare disease, but also to identify new analysis pipelines that can speed this process for other labs.

Through this collaboration, we will continue to advance the scientific communitys understanding of rare disease and to support both patients enrolled in this study and others whose exomes were sequenced previously through our Patient for Life program, said Tom Schoenherr, CEO of Ambry Genetics. This collaboration is an example of our steadfast commitment to excellence in genomics and relentless pursuit of innovation, which has been a driving force behind our work since we launched our first clinical offering for rare disease diagnosis more than 20 years ago.

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Ambry Genetics and PacBio Announce Collaboration To Sequence up to 7000 Human Genomes - Technology Networks

Genetics

Study: Good Sleep Habits Linked to Lower Heart Disease Risk – Health.com

Having a consistent sleep schedule and regularly getting enough shuteye may lower your risk of cardiovascular disease, coronary heart disease, and stroke, according to new research.

Its well-established that sleep is a fundamental part of health, and not getting enough sleep can be harmful to your health. Disrupted sleep due to shift work has been linked to a higher risk of developing diabetes or having a heart attack. And getting too much or too little sleep has been linked to a higher risk of infection.

This latest study, published in JAMA Network Open in April, similarly came to the conclusion that good sleep is linked to better health. But interestingly, they found that the association between consistently good sleep and lowered risk of cardiovascular disease was true regardless of a persons genetic risk for developing the disease.

Our results further suggested that individuals with a higher genetic predisposition may benefit from persistent favorable sleep patterns, Xiaomin Zhang, MD, PhD, MPH, study author and professor of occupational and environmental health at the Huazhong University of Science and Technology Tongji Medical College, told Health.

Heres what experts had to say about the new research, the connection between healthy sleep patterns and heart health, and tips for consistently sleeping well.

Toa55 / Getty Images

This new study builds upon research published last year in the European Heart Journal, which found that people who maintained healthy sleep patterns over a two to five year period reduced their risk of cardiovascular disease.

Further investigating this finding, Zhang and her colleagues collected data on the sleep habits of more than 15,300 people in China who were retired. The average age in the cohort was about 66 years old, and about 58% were women. None of the participants had cancer or cardiovascular disease when the study began.

Participants filled out questionnaires and had a medical exam at the beginning of the study, and then again five years later.

The questionnaire asked people to report their sleeping habits, including their bedtime, sleep duration, sleep quality, and any midday napping. From there, the research team used data to determine if a persons sleep habits were persistently favorable or unfavorable.

Favorable sleep meant people were following four habits: getting 7 to 8 hours of sleep every night, going to bed between 10:00 p.m. and midnight, reporting good or fair sleep quality, and taking a midday nap for no more than an hour.

In addition to these sleep questionnaires, researchers used genotyping to assess participants genetic risk for developing stroke and coronary heart disease.

In the end, Zhang and her colleagues found that people who reported consistently favorable sleep habits had a lower risk of developing coronary heart disease, cardiovascular disease, and stroke. This was true regardless of a persons genetic risk for these diseases.

People who reported favorable sleeping habits at both points in the study had a 16% lower risk of coronary heart disease and a 34% lower risk of stroke.

For participants who both slept well consistently and had a low genetic risk, they saw a 35% lower risk of coronary heart disease and a 52% lower risk of stroke as compared to people on the other end of the spectrum, who were at high risk for cardiovascular disease and had poor sleep habits.

It is not surprising, but it is good additional supportive data to indicate the link between sleep and cardiovascular disease, Ashish Sarraju, MD, a staff preventive cardiologist at Cleveland Clinic who was not involved with the research, told Health.

Importantly, the studys findings emphasize that even people with a high genetic risk for stroke and coronary heart disease risk can lower their risk for these conditions by maintaining good sleep habits.

Of course, those at genetic risk are likely to have an overall higher risk for cardiovascular disease, said Sarraju. But there is no reason to believe that sleep is less important in those patients.

The link between sleep health and heart health is a strong one. The American Heart Association lists sleep on its Lifes Essential 8 list, which includes the most significant lifestyle factors for preserving cardiovascular health.

According to Zhang, lack of sleep or inconsistent sleep habits may affect heart health by causing inflammation and metabolic imbalances, or disruptions in how the body metabolizes food and gets rid of waste.

Poor sleep hygiene also disrupts circadian rhythm, which has been linked to issues such as hypertension.

Sleep patterns can be linked to high blood pressure and stress, Sarraju added.

Beyond just unfavorable sleep, not getting enough shuteye due to sleep disorders can also impact heart health. Specifically, obstructive sleep apnea is linked to both poor sleep and increased risk for cardiovascular disease.

Because of these associations, doctors should ask about sleep quality and quantity as they assess a persons cardiovascular disease risk, Sarraju said, especially if the patient has high blood pressure. Addressing these poor sleep patterns or sleep disorders will likely, in turn, improve heart health.

Even if a person does have a higher risk of developing cardiovascular disease, this new study and others show that patients are not 100% chained to genetics, Sarraju explained. Modifying risk factors still has an effect in decreasing cardiovascular disease in those patients.

Getting good sleep regularly is often easier said than done. Adults should get between seven and nine hours of sleep each night, and its recommended that people go to bed and wake up at the same time every day. But this consistency may not be as easy for people who work, people who are raising children, or others with busy, changing schedules.

But whenever possible, people should follow recommendations for good quality sleep from the Centers for Disease Control and Prevention (CDC). These guidelines include exercising during the day, avoiding large meals, caffeine, and alcohol before bed, sleeping in a quiet, dark, and cool room, and avoiding screens 30 minutes before bedtime.

In general, these are actionable steps that people can incorporate into their nighttime routinesthis might be especially good news for people who are genetically predisposed to heart disease.

Genetic factors are inherent, Zhang said. Sleep patterns can be actively managed and adjusted.

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Study: Good Sleep Habits Linked to Lower Heart Disease Risk - Health.com

Genetics

Study finds gene variants tied to breast cancer risk in Black women – STAT

Hundreds of genetic variants can nudge someones risk of breast cancer up or down or towards a particular subtype. The studies identifying those gene variants, though, have largely involved people with European ancestry and thus give a less accurate picture of breast cancer risk for people who are not white.

Thats beginning to change. Last week, researchers published a genome-wide association study on breast cancer in roughly 40,000 people of African descent in Nature Genetics, marking a leap forward in scientists knowledge of breast cancer genetics in people of African ancestry.

Before we started this study in 2016, there were just several thousand cases for Black Americans. It was a very small number, said Wei Zheng, the studys senior investigator and a cancer epidemiologist at Vanderbilt University. This study combined data from dozens of other studies and included genetic data for thousands of new participants, making it the largest combined breast cancer genetics study done with people with African ancestry.

Specifically, the study compiled data from about 30 different studies investigating breast cancer in African or African American people. About 18,000 of them had breast cancer, while the other 22,000 were healthy controls, and investigators were able to scour their genetic data for specific variations that seemed closely related to breast cancer. The statistical power that comes with such numbers enabled the team to make two key advances.

First, the team found 12 loci, or locations in the genome, that showed a significant association with breast cancer. Of those, the team identified variants of three genes that appear to increase the risk of triple negative breast cancer, one of the most aggressive subtypes. Since everyone has two copies or alleles of each gene, that means someone could have anywhere between one and six risk-related alleles of these three genes. Those who had all six risk-related alleles had roughly double the chance of getting triple negative breast cancer than those who only had three.

That could provide a foothold for scientists to begin predicting who might get this aggressive form of breast cancer, and it might offer an opportunity to better understand the biology of triple negative breast cancer by highlighting genes that seem to be important. Finally, we have enough data to drill down to estrogen negative and triple negative breast cancer, which are twice as common in the African American population as any other population, said Julie Palmer, an author of the study and a cancer researcher at Boston University.

The other advance came when the researchers used the data to build a breast cancer risk prediction model for people with African ancestry. Such models take into account hundreds of different genetic variants that can slightly push breast cancer risk up, adding them all up into a polygenic risk score.

In the past, these scores always performed better for white people than Black people, mainly because theres so much more research done in people with European ancestry a combined total of more than 100,000 participants for breast cancer. Polygenic risk scores have had an AUC, a measure of the models performance, of about 0.63 for people with European ancestry compared to 0.58 for the African ancestry population. When researchers combined the data from this study into their new model, however, that figure rose to 0.60. That equates to the model being able to correctly distinguish between someone whos likely to get breast cancer and someone who isnt about 60% of the time.

Even if this work is validated in other studies, as it still needs to be, that figure is not too useful for most individuals. An astute observer might note an AUC of 0.63 is only passably better than a coin toss. Thats an indication polygenic risk scores dont perform as well overall as scientists would like even at their best. When polygenic risk scores are combined with other breast cancer risk factors, like age of first childbirth or breast density, were still not very good at predicting breast cancer, Palmer said.

But research is continually improving on that. The hope is, one day, these scores will help scientists build tools that can reliably distinguish people who are more likely to get breast cancer and thus might have more to gain by beginning screening earlier or more frequently. Or, conversely, they could help weed out people who arent likely to get breast cancer and could thus screen less. If you dont need it, then why do it? said Laura Fejerman, a cancer researcher and epidemiologist at the University of California, Davis.

Polygenic risk scores might already be able to provide some of that context for a small minority of people, Fejerman added. For the 1% of people with the highest polygenic risk, their lifetime risk was a little bit above 30%, Fejerman said. That could be an argument for them to screen more often, even if they had no other risk factors. If you learn that, you might be more on top of your screening than most people who maybe let three years pass. So, if you could get the highest-risk women to screen every year, that would be a big benefit.

Without datasets in non-European ancestry populations, other racial demographic groups could be left out of that progress. In that sense, this new paper is definitely a big step forward for achieving racial equity, said Swati Biswas, a statistician and cancer researcher at the University of Texas at Dallas who did not work on the study.

In particular, the data are needed if scientists ever hope to create a unified polygenic risk score that works for everyone. At the moment, many models rely on racial categorization Black people use an African ancestry model; white people use a European model. But using such models in clinical practice isnt optimal, pointed out Jennifer James, a sociologist who studies breast cancer and bioethics at the University of California, San Francisco.

Imagine someone whose ancestry is 5% African and 95% European, but who also happened to inherit breast cancer risk alleles that were only found in the African ancestry population. That would mean the African ancestry polygenic risk model might work better for them, even if they didnt identify as Black themselves. You could be 1% Black, but the one thing you got was that allele, James said. We need to move towards a unified polygenic risk score.

That still wont be enough to end the breast cancer mortality gap between Black and white people, even if scientists created a perfectly accurate polygenic risk model, James added. Thats because part of the reason for the disparity has to do with the health care system writ large, not subtle biological differences across populations.

We know Black women have a longer time to diagnosis, longer time from diagnosis to treatment, James said. If everyone had equal access to healthcare, that would do more to close gaps in mortality than tweaking prediction models. I want when someone finds a lump in their breast or needs a mammogram, they have equal access to care.

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Study finds gene variants tied to breast cancer risk in Black women - STAT

Genetics

Asking the Right Questions about Genetic Engineering – The University of Chicago Divinity School

Reservations about human genetic engineering generally fall into two camps: those who worry it is unnatural and those who worry it will be unfair. The ways these concerns are deployed are often unhelpful, but they point us toward real areas of concern where religious voices are valuable.

We can wave aside the superficial versions of these worries easily. The first is far too general in its condemnation. Genetic engineering is unnatural, but so is nasal spray. The whole project of medicine is an effort to make us healthier than we find ourselves naturally. If we are going to condemn human bioengineering because it is unnatural, wed have to find an argument that would not condemn all medical technology.

The second concern, rather than condemning too much technology, is often not about technology at all. Walter Isaacson, in an interview after writing a book on the subject, commented that, One of the problems when people discuss technology is that they often speak as if theyre afraid of technology when what theyre afraid of is capitalism. When my students share worries about an engineered human future, they are not usually afraid of genetics as some scary frontier they dont remember a time when we couldnt program DNA like computer code. What older generations may assume is still science fiction using an engineered virus to alter genes and cure a disease! my students simply take for granted (these techniques have already received FDA approval). No, my students tend to be afraid that new technologies will reinforce existing inequalities and systems of oppression. They arent worried about genetic technology; they are worried about genetic capitalism.

Worries about capitalism dominate dystopian depictions of our bioengineered future. My students regularly reference Gattaca, a movie which depicts a future with a strict class division between those who have been genetically engineered and those made the old-fashioned way, with only the former given access to professional opportunities. (Students bring up Gattaca often enough that I suspect high school biology teachers must all show the film in class).

In stories like Gattaca, nothing goes wrong with the bioengineering itself (stories of experimental medicine going wrong and producing zombies is a whole other genre). The problem in these movies is that successful bioengineering literally incarnates social inequality. These movies make visible the present reality that inheritance restricts our destinies. They are myths about capitalism as much or more than technology.

So, the objection that genetic technology is unnatural can fail because it criticizes too much technology, and the objection that it is unfair is inadequate because it may not criticize technology at all. But each of these concerns can point in a helpful direction, and more sophisticated versions of these arguments deserve consideration.

First, it is a thin definition of nature that calls all uses of technology unnatural. But there are different ways in which a technology can alter nature. Some technologies facilitate and reinforce existing relationships of care; others warp such relationships. To treat a childs cancer with chemotherapy isnt natural, but caring for a sick child certainly is. To select your future childs traits from a menu seems unnatural in a fundamentally different way. The former uses new technology to aid an ancient vocation of care. The latter introduces a novel power dynamic into intimate relationships, changing parents into consumers and children into products. Calling such engineering unnatural may be a shorthand for legitimate concerns about how these practices could distort relationships at the heart of human life.

Second, there are concerns about capitalism and genetic engineering that pertain directly to these technologies. Unfortunately, our ideas about justice have become so dominated by concerns about social oppression that we struggle to see anything underneath relations of power. We can forget the biology beneath sociality. If our moral aspirations are limited to achieving equity, we may not anticipate that a human population which radically alters its biology might be equally and freely victim to its own lack of foresight. We have an array of needs food, water, shelter as a result of having bodies, needs that we should strive to meet equitably. But bodies are more than things with needs; the fact that we are genetically diverse, ecological bodies shapes our goods and our experience of them. Genetic variation undergirds our social life in ways we may not recognize until they are removed by the flattening effects of biotechnology. I worry that, if we miss that fact, we may welcome Huxleys brave new world, as long as it comes with universal engineering and single-payer soma distribution.

We might imagine a just biotechnological future in which all races and classes have access to opportunities to engineer their children. But such a society, despite its social justice, may be worse off than one without genetic engineering, even if it is healthier, taller, and more athletic. We shouldnt just worry about capitalism making the future unfair. We should also worry about consumerism bioengineering a banal human monoculture (a concern that is intrinsic to the potential homogenizing effects of the technology). Yes, we should worry about a future where some people are born into a genetic ghetto, but we should probably also worry about a future where all people are born into a genetic suburb. Seeing that danger requires that we think about more than social justice when we think about genes and capitalism.

Refocusing moral concern on what is natural and bodily is a task for which religions may be critical. One reason why I value the work of religious ethicists in addition to philosophers is that religions often maintain closer contact with the messiness of bodily life. Religious communities tend to remain in touch, through spiritual disciplines, ritual, and confession, with the biological basis of human flourishing. They should be less prone to forget the limits that bodies put on agency. Religions can help us articulate visions of the human good that have positive content, rather than just negative condemnations of injustice. They can help us learn the lesson that there are realities sacred, natural, or both before which we ought to hold back, that there are mysteries to be respected, not removed.

Featured image by National Cancer Institute/Unsplash

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Asking the Right Questions about Genetic Engineering - The University of Chicago Divinity School