Faculty Publication: Assistant Professor of Biology B谩rbara Domingues Bitarello
Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus
Authors: Iain Mathieson, Felix R. Day, Nicola Barban, Felix C. Tropf, David M. Brazel, eQTLGen Consortium, BIOS Consortium, Ahmad Vaez, Natalie van Zuydam, B谩rbara D. Bitarello, Eugene J. Gardner, Evelina T. Akimova, Ajuna Azad, Sven Bergmann, Lawrence F. Bielak, Dorret I. Boomsma, Kristina Bosak, Marco Brumat, Julie E. Buring, David Cesarini, Daniel I. Chasman, Jorge E. Chavarro, Massimiliano Cocca, Maria Pina Concas, George Davey Smith, Gail Davies, Ian J. Deary, T玫nu Esko, Jessica D. Faul, FinnGen Study, Oscar Franco, Andrea Ganna, Audrey J. Gaskins, Andrea Gelemanovic, Eco J. C. de Geus, Christian Gieger, Giorgia Girotto, Bamini Gopinath, Hans J枚rgen Grabe, Erica P. Gunderson, Caroline Hayward, Chunyan He, Diana van Heemst, W. David Hill, Eva R. Hoffmann, Georg Homuth, Jouke Jan Hottenga, Hongyang Huang, Elina Hypp缨nen, M. Arfan Ikram, Rick Jansen, Magnus Johannesson, Zoha Kamali, Sharon L. R. Kardia, Maryam Kavousi, Annette Kifley, Tuomo Kiiskinen, Peter Kraft, Brigitte K眉hnel, Claudia Langenberg, Gerald Liew, Lifelines Cohort Study, Penelope A. Lind, Jian鈥檃n Luan, Reedik M盲gi, Patrik K. E. Magnusson, Anubha Mahajan, Nicholas G. Martin, Hamdi Mbarek, Mark I. McCarthy, George McMahon, Sarah E. Medland, Thomas Meitinger, Andres Metspalu, Evelin Mihailov, Lili Milani, Stacey A. Missmer, Paul Mitchell, Stine M酶llegaard, Dennis O. Mook-Kanamori, Anna Morgan, Peter J. van der Most, Ren茅e de Mutsert, Matthias Nauck, Ilja M. Nolte, Raymond Noordam, Brenda W. J. H. Penninx, Annette Peters, Patricia A. Peyser, Ozren Pola拧ek, Chris Power, Ajka Pribisalic, Paul Redmond, Janet W. Rich-Edwards, Paul M. Ridker, Cornelius A. Rietveld, Susan M. Ring, Lynda M. Rose, Rico Rueedi, Vallari Shukla, Jennifer A. Smith, Stasa Stankovic, K谩ri Stef谩nsson, Doris St枚ckl, Konstantin Strauch, Morris A. Swertz, Alexander Teumer, Gudmar Thorleifsson, Unnur Thorsteinsdottir, A. Roy Thurik, Nicholas J. Timpson, Constance Turman, Andr茅 G. Uitterlinden, Melanie Waldenberger, Nicholas J. Wareham, David R. Weir, Gonneke Willemsen, Jing Hau Zhao, Wei Zhao, Yajie Zhao, Harold Snieder, Marcel den Hoed, Ken K. Ong, Melinda C. Mills, and John R. B. Perry
Source: Nature Human Behaviour, DOI: 10.1038/s41562-023-01528-6, March 2023
Type of Publication: Article
Abstract: Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success.