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

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.I.; Bosak, K.; Brumat, M.; Buring, J.E.; Cesarini, D.; Chasman, D.I.; Chavarro, J.E.; Cocca, M.; Concas, M.P.; Davey Smith, G.; Davies, G.; Deary, I.J.; Esko, T.; Faul, J.D.; Franco, O.; Ganna, A.; Gaskins, A.J.; Gelemanovic, A.; de Geus, EJC; 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.; Hyppӧnen, E.; Ikram, M.A.; Jansen, R.; Johannesson, M.; Kamali, Z.; Kardia, SLR; Kavousi, M.; Kifley, A.; Kiiskinen, T.; Kraft, P.; Kühnel, B.; Langenberg, C.; Liew, G.; Lind, P.A.; Luan, J.; Mägi, R.; Magnusson, PKE; Mahajan, A.; Martin, N.G.; Mbarek, H.; McCarthy, M.I.; McMahon, G.; Medland, S.E.; Meitinger, T.; Metspalu, A.; Mihailov, E.; Milani, L.; Missmer, S.A.; Mitchell, P.; Møllegaard, S.; Mook-Kanamori, D.O.; Morgan, A.; van der Most, P.J.; de Mutsert, R.; Nauck, M.; Nolte, I.M.; Noordam, R.; Penninx, BWJH; Peters, A.; Peyser, P.A.; Polašek, 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.; Stefánsson, 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.; Zhao, Y.; Snieder, H.; den Hoed, M.; Ong, K.K.; Mills, M.C.; Perry, JRB

doi:10.1038/s41562-023-01528-6

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

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Serval ID

serval:BIB_F6DE9D216FAD

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature human behaviour

Author(s)

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.I., Bosak K., Brumat M., Buring J.E., Cesarini D., Chasman D.I., Chavarro J.E., Cocca M., Concas M.P., Davey Smith G., Davies G., Deary I.J., Esko T., Faul J.D., Franco O., Ganna A., Gaskins A.J., Gelemanovic A., de Geus EJC, 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., Hyppӧnen E., Ikram M.A., Jansen R., Johannesson M., Kamali Z., Kardia SLR, Kavousi M., Kifley A., Kiiskinen T., Kraft P., Kühnel B., Langenberg C., Liew G., Lind P.A., Luan J., Mägi R., Magnusson PKE, Mahajan A., Martin N.G., Mbarek H., McCarthy M.I., McMahon G., Medland S.E., Meitinger T., Metspalu A., Mihailov E., Milani L., Missmer S.A., Mitchell P., Møllegaard S., Mook-Kanamori D.O., Morgan A., van der Most P.J., de Mutsert R., Nauck M., Nolte I.M., Noordam R., Penninx BWJH, Peters A., Peyser P.A., Polašek 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., Stefánsson 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., Zhao Y., Snieder H., den Hoed M., Ong K.K., Mills M.C., Perry JRB

Working group(s)

eQTLGen Consortium, BIOS Consortium, FinnGen Study, Lifelines Cohort Study

Contributor(s)

van Heemst D., van der Most P.J.

ISSN

2397-3374 (Electronic)

ISSN-L

2397-3374

Publication state

Published

Issued date

05/2023

Peer-reviewed

Oui

Volume

Number

Pages

790-801

Language

english

Notes

Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish

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.

Keywords

Child, Female, Humans, Aging/physiology, Fertility/genetics, Menopause/genetics, Reproduction/genetics, Selection, Genetic

OAI-PMH

oai:serval.unil.ch:BIB_F6DE9D216FAD

DOI

10.1038/s41562-023-01528-6

Pubmed

36864135

Web of science

000955741600006

Create date

13/03/2023 12:47