Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus.
Journal
Nature human behaviour
ISSN: 2397-3374
Titre abrégé: Nat Hum Behav
Pays: England
ID NLM: 101697750
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
30
06
2021
accepted:
12
01
2023
medline:
24
5
2023
pubmed:
3
3
2023
entrez:
2
3
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36864135
doi: 10.1038/s41562-023-01528-6
pii: 10.1038/s41562-023-01528-6
doi:
Substances chimiques
FADS2 protein, human
EC 1.14.19.3
FADS1 protein, human
EC 1.14.19.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
790-801Subventions
Organisme : Medical Research Council
ID : MC_UU_00006/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00006/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00032/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T030852/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Organisme : Medical Research Council
ID : G9815508
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12015/2
Pays : United Kingdom
Investigateurs
Diana van Heemst
(D)
Peter J van der Most
(PJ)
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
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