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Genome-Wide Analysis ID’s Genetic Effects on Reproductive Success & Ongoing Natural Selection at FADS Locus; FADS1/2 Allele Represents Perhaps Only Example of Genetic Variant with Evidence of Both Ancient & Ongoing Selection, Scientists Say at ASHG 2020

An international team of researchers who identified genetic variants associated with reproductive success say their findings could highlight mechanisms underlying fertility and infertility. In addition, their analyses detected genetic alleles under present-day selection, providing an insight into the nature of ongoing natural selection in humans. Iain Mathieson, PhD, a population geneticist at the University of Pennsylvania, presented the results of the study at the American Society of Human Genetics 2020 Virtual Meeting. The title of his presentation was “Genome-Wide Analysis Identifies Genetic Effects on Reproductive Success and Ongoing Natural Selection at the FADS Locus,” and was delivered in the ASHG’s Thursday morning session “Natural Selection on Polygenic Traits and Omics.” “This study is of interest in relation to our findings on reproductive biology and potential links to infertility,” says co-author of the study Melinda Mills, PhD, Director of the Leverhulme Centre for Demographic Science at the University of Oxford (UK). “But it also empirically tests one of the most gripping and fundamental questions asked by scientists across many disciplines and decades: Is there evidence of ongoing natural selection in humans and, if so, what is it and how does it operate?” The new study builds upon previous research on the genetic bases of reproductive behavior (timing and number of children) and reproductive development to identify individual genetic determinants of number of children ever born or childlessness. The researchers performed genome-wide association studies (GWAS) in up to 785,604 individuals of European ancestry and identified 43 genetic loci associated with either number of children ever born or childlessness. These loci span diverse aspects of reproductive biology across the lifespan, including puberty timing, age at first birth, sex hormone levels, sexuality, and age at menopause. The findings demonstrate that diverse biological mechanisms contribute to reproductive success, implicating both neuroendocrine and behavioral influences. Ultimately, the researchers believe this might lead to a better understanding of the biology of reproduction and perhaps the genetic basis of infertility.

Furthermore, by integrating these findings with data from ancient selection scans, the researchers were able to identify a unique example of an allele – known as FADS1/2 – that was under selection in our ancient past and remains under selection today. [Editor’s Note: FADS is the abbreviation for “fatty acid desaturase.”]

“Independent research has shown that this allele has been under selection for many thousands of years, potentially linked to changes in diet around the time of the transition to agriculture,” says Dr. Mathieson. “Therefore, it represents perhaps the only example of a genetic variant with evidence of both historical and ongoing selection.”

Dr. Mathieson says the study raises a number of questions to look into in the future, such as why the FADS1/2 locus is under selection. Experiments in animal models might provide a clue: Knocking out the FADS1 gene in mice leads to both male and female infertility.

Additionally, Dr. Mills points out that this study, like nearly 90% of contemporary genetic research, is limited by its use of data from only individuals of European ancestry.

“This is problematic, as we and others have addressed,” she says. “Future extensions of this work will examine diverse non-European populations.”

REFERENCE

Mathieson, I., Day, F.R., Barban, N., Tropf, F.C., Brazel, D., eQTLGen Consortium, BIOS Consortium, Vaez, A., van Zuydam, N., Bitarello, B.D., Snieder, H., den Hoed, M., Ong, K.K., Mills, M., Perry, J.R., and Human Reproductive Behaviour Consortium. (Date). Abstract: Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus. Presented at the American Society of Human Genetics 2020 Virtual Meeting.

AMERICAN SOCIETY OF HUMAN GENETICS (ASHG)

Founded in 1948, the American Society of Human Genetics (ASHG) is the primary professional membership organization for human genetics specialists worldwide. Its nearly 8,000 members include researchers, academicians, clinicians, laboratory practice professionals, genetic counselors, nurses, and others with an interest in human genetics. The Society serves scientists, health professionals, and the public by providing forums to: (1) share research results through the ASHG Annual Meeting and in The American Journal of Human Genetics; (2) advance genetic research by advocating for research support; (3) educate current and future genetics professionals, health care providers, advocates, policymakers, educators, students, and the public about all aspects of human genetics; and (4) promote genetic services and support responsible social and scientific policies. For more information, visit: http://www.ashg.org.

[ASHG press release] [ASHG 2020 Virtual Annual Meeting]