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Mathieson, I.* ; Day, F.R.* ; Barban, N.* ; Tropf, F.C.* ; Brazel, D.M.* ; Vaez, A.* ; van Zuydam, N.* ; Bitarello, B.D.* ; Gardner, E.J.* ; Akimova, E.T.* ; Azad, A.* ; Bergmann, S.* ; Bielak, L.F.* ; Boomsma, D.* ; Bosak, K.* ; Brumat, M.* ; Buring, J.E.* ; Cesarini, D.* ; Chasman, D.* ; Chavarro, J.E.* ; Cocca, M.* ; Concas, M.P.* ; Davey Smith, G.* ; Davies, G.* ; Deary, I.J.* ; Esko, T.* ; Faul, J.D.* ; Franco, O.H.* ; Ganna, A.* ; Gaskins, A.J.* ; Gelemanović, A.* ; de Geus, E.J.C.* ; Gieger, C. ; Girotto, G.* ; Gopinath, B.* ; Grabe, H.J.* ; Gunderson, E.P.* ; Hayward, C.* ; He, C.* ; van Heemst, D.* ; Hill, W.D.* ; Hoffmann, E.R.* ; Homuth, G.* ; Hottenga, J.J.* ; Huang, H.* ; Hyppoenen, E.* ; Ikram, M.A.* ; Jansen, R.* ; Johannesson, M.* ; Kamali, Z.* ; Kardia, S.L.R.* ; Kavousi, M.* ; Kifley, A.* ; Kiiskinen, T.* ; Kraft, P.* ; Kühnel, B. ; Langenberg, C.* ; Liew, G.* ; Lind, P.A.* ; Luan, J.* ; Mägi, R.* ; Magnusson, P.K.E.* ; Mahajan, A.* ; Martin, N.G.* ; Mbarek, H.* ; McCarthy, M.* ; McMahon, G.* ; Medland, S.E.* ; Meitinger, T. ; Metspalu, A.* ; Mihailov, E.* ; Milani, L.* ; Missmer, S.A.* ; Mitchell, P.* ; Mollegaard, S.* ; Mook-Kanamori, D.O.* ; Morgan, A.* ; van der Most, P.J.* ; de Mutsert, R.* ; Nauck, M.* ; Nolte, I.M.* ; Noordam, R.* ; Penninx, B.W.J.H.* ; Peters, A. ; Peyser, P.A.* ; Polasek, O.* ; Power, C.* ; Pribisalic, A.* ; Redmond, P.* ; Rich-Edwards, J.W.* ; Ridker, P.M.* ; Rietveld, C.A.* ; Ring, S.M.* ; Rose, L.M.* ; Rueedi, R.* ; Shukla, V.* ; Smith, J.A.* ; Stankovic, S.* ; Stefansson, K.* ; Stöckl, D. ; Strauch, K. ; Swertz, M.A.* ; Teumer, A.* ; Thorleifsson, G.* ; Thorsteinsdottir, U.* ; Thurik, A.R.* ; Timpson, N.J.* ; Turman, C.* ; Uitterlinden, A.G.* ; Waldenberger, M. ; Wareham, N.J.* ; Weir, D.R.* ; Willemsen, G.* ; Zhao, J.H.* ; Zhao, W.N.* ; Zhao, Y.* ; Snieder, H.* ; den Hoed, M.* ; Ong, K.K.* ; Mills, M.C.* ; Perry, J.R.B.*

Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus.

Nat. Hum. Behav. 7, 790-801 (2023)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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. Mathieson et al. carried out a genome-wide association study of reproductive success (number of children born) in humans, revealing the importance of diverse neuro-endocrine and behavioural factors.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Term Balancing Selection; Quality-control; Association; Variants; Gwas; Heritability; Metaanalysis; Adaptation; Signatures; Eqtl
ISSN (print) / ISBN 2397-3374
e-ISSN 2397-3374
Journal Nature human behaviour
Quellenangaben Volume: 7, Issue: 5, Pages: 790-801 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Human Genetics (IHG)
Institute of Genetic Epidemiology (IGE)
Grants ESRC
LabEx Ecodec ANR
Leverhulme Centre for Demographic Science
Leverhulme Trust