Repronews #35: A European review of polygenic screening
Scandinavian mega-study of mental & cardiometabolic disorders; 100s genes may influence breast cancer risk, aggressiveness; Atlas for precision space medicine; Regnault-Roger’s “Biotech Challenges”
Welcome to the latest issue of Repronews! Highlights from this week’s edition:
Repro/genetics
European scholars’ review of epidemiological, clinical, and ethical issues in polygenic screening
Genetic Studies
Mega-study of 17 million Scandinavians found genetic factors contributed about 50% to the comorbidity (simultaneous presence) of certain mental disorders (schizophrenia, affective disorders, and autism spectrum disorder) with cardiometabolic disorders (such as stroke and heart failure)
Study finds hundreds of genes may influence breast cancer risk and aggressiveness
The Space Omics and Medical Atlas (SOMA) has multiplied by 10 the amount of public data on space “omics,” i.e. genomic, epigenomic, microbiome, and other data on astronauts and the impact of space on humans.
Further Learning
Top French crop scientist Catherine Regnault-Roger’s Biotech Challenges outlines the history and potential of agricultural biotech, including CRISPR.
Repro/genetics
“Screening embryos for polygenic disease risk: a review of epidemiological, clinical, and ethical considerations” (Human Reproduction Update)
A group of European scholars conducted a broad review on polygenic embryo screening for disease risk (PES or PGT-P).
Recent advances have made genome-wide genotyping of IVF embryos feasible and affordable, raising the possibility of screening embryos for their risk of polygenic diseases such as breast cancer, hypertension, diabetes, or schizophrenia. The technology is already available in some countries.
The main theoretical benefit of PES is a reduction in lifetime polygenic disease risk for children born after screening. The magnitude of the risk reduction has been predicted based on statistical modelling, simulations, and sibling pair analyses. Results based on all methods suggest that under the best-case scenario, large relative risk reductions are possible for one or more diseases.
As these models abstract several practical limitations, the realized benefits may be smaller, particularly due to a limited number of embryos and unclear future accuracy of the risk estimates.
Possible negative personal harms of PES include an unindicated IVF treatment, a possible reduction in IVF success rates, and patient confusion, incomplete counseling, and choice overload.
The authors argue possible societal harms include discarded embryos, an increasing demand for “designer babies,” overemphasis of the genetic determinants of disease, unequal access, and lower utility in people of non-European ancestries.
The authors argue that because of practical limitations and potential harms, particularly unnecessary IVF treatments and discarded viable embryos, PES should be offered only within a research context before further clarity is achieved regarding its balance of benefits and harms.
More on repro/genetics:
“The use of expanded carrier screening in reproductive medicine” (Royal College of Obstetricians and Gynaecologists)
“Genome sequencing differentiates a paracentric inversion from a balanced insertion enabling more accurate preimplantation genetic testing” (AOGS)
Erik Widen et al, “Correspondence on “Clinical utility of polygenic risk scores for embryo selection: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG)” by Grebe et al” (GIM)
Theresa Greb et al, “Response to Widen et al” (GIM)
“It is too soon for clinical trials on artificial wombs” (Scientific American)
“Practical applications of AI in IVF laboratories: Addressing key challenges and opportunities” (MIM Fertility)
Genetic Studies
“Quantifying the relative importance of genetics and environment on the comorbidity between mental and cardiometabolic disorders using 17 million Scandinavians” (Nature Communications)
Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders, such as heart failure and stroke. Reasons for this comorbidity are still poorly understood.
The study used nation-wide health records and near-complete genealogies in Denmark and Sweden (covering 17 million people) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders.
Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with cardiometabolic disorders.
The comorbidity of attention-deficit/hyperactivity disorder and anorexia with cardiometabolic disorders was mainly or fully driven by environmental factors.
Hundreds of genetic variants may influence breast cancer risk and aggressiveness (PET)
Researchers looked at the genetic sequences of breast cancer tumours from 5529 women, along with the sequence of the DNA they were born with, to better understand how genetics influence the subtype of breast cancer that develops.
“We wanted to understand how inherited DNA might sculpt how a tumour evolves,” said Dr. Kathleen Houlahan of Stamford University and lead researcher of the paper published in Science.
The findings suggest hundreds of other genetic variants could affect cancer risk and aggressiveness.
“Our findings not only explain which subtype of breast cancer an individual is likely to develop,” said Dr. Houlahan, “but they also hint at how aggressive and prone to metastasising that subtype will be. Beyond that, we speculate that these inherited variants may influence a person’s risk of developing breast cancer. However, future studies will be needed to examine this.”
The Space Omics and Medical Atlas (SOMA) and international astronaut biobank (Nature)
Spaceflight induces molecular, cellular, and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space.
The Space Omics and Medical Atlas (SOMA) is an integrated data and sample repository for clinical, cellular, and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study, JAXA CFE study, SpaceX Inspiration4 crew, Axiom, and Polaris.
SOMA represents a >10-fold increase in publicly available space omics data.
The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiome data sets.
SOMA can help accelerate precision aerospace medicine, bringing needed health monitoring, risk mitigation, and countermeasures data for upcoming lunar, Mars, and exploration-class missions.
More on genetic studies:
“Disentangling multiple sclerosis heterogeneity in the French territory among genetic and environmental factors via Bayesian heritability analysis” (MS)
“Meta-analysis of genome-wide association studies reveals genetic mechanisms of supraventricular arrhythmias” (C:GPM)
Lack of diversity data standing in way of gene-editing medicine (Vox)
Further Learning
Book review: Biotech Challenges by “tech optimist” Catherine Regnault-Roger (GLP)
Catherine Regnault-Roger, Professor Emeritus at the University of Pau and a Member of the French Academy of Agriculture, has written Biotech Challenges, a short book (150 pages) on the history of agricultural biotechnology and recent development of New Genomic Techniques (NGTs) in agriculture, including CRISPR gene editing. She is a former member of the Scientific Committee of France’s High Council of Biotechnologies.
The first wave of the agricultural biotechnology revolution, in the 1980s and 1990s. Driven by advances in genetically modifying organisms (GMOs), transgenesis, and random mutagenesis, first-generation of genetic engineering tools yielded many important farming advances such as weed and pest control.
The book covers animal and plant applications of biotech, profiling leading researchers and their breakthrough products.
Biotech Challenges also covers political aspects: the disagreements among scientists, farmers, and environmentalists on the benefits and dangers of agricutlrual debates; divergent national approaches grounded more in politics than science; and geopolitical debates on local control of food production, national sovreignty, and international competition.
The second wave of biotech techniques are more precise, and have been revolutionizing both agriculture and human and veterinary medicine.
Countries around the world have greeted these innovations very differently, reflecting their internal politics, trade needs, cultural traditions, and their comfort level with change.
For many years, sub-Saharan African countries resisted adopting genetically engineered technology, fearing a frosty reaction from the European Union. Only recently, with the development of NGTs, have the African countries shaken loose of Europe’s influence to launch biotechnology research projects of their own.
The author, a “techno optimist” argues the agricultural biotech revolution will especially benefit developing countries, unless it is blocked for political reasons. The EU in particular is urged to adopt a more favorable approach towards agricultural biotech.
The book was originally published in French as Enjeux biotechnologiques, des OGM à l’édition du génome by Presses des Mines (Paris).
More on human nature, evolution, and biotech:
“More births, please”: Richard Hanania interview Dan Hess (@MoreBirths) (Hanania Newsletter)
Louise Perry, “The quiet return of eugenics” (The Spectator)
Agriculture
Editorial: “Cis-editing for all” (Nature Biotechnology)
“CRISPR improves a crop that feeds billions: The gene-editing system, normally used to disrupt a gene, is applied to improve the function of a gene in rice” (Nature)
“China adds gene-edited wheat to growing biotech crop list” (AgDaily)
Report: “Policy support for alternative proteins could free up 44% of European land and boost self-sufficiency” (Green Queen)
Disclaimer: The Genetic Choice Project cannot fact-check the linked-to stories and studies, nor do the views expressed necessarily reflect our own.
Why did African countries not use GMOs? Most of them are food insecure anyways. It's not like they're exporting to Europe anyways. Why the hell would they influenced by Europe on this matter when developing Asia went ahead and used GMOs except India.