Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour

doi:10.1038/s41562-021-01135-3

Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour

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Producción científica: Article › revisión exhaustiva

120 Citas (Scopus)

Resumen

Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5–6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4–14%] for women born in 1940 to 22% [CI = 19–25%] for those born in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility and spermatid differentiation. Our findings suggest that polycystic ovarian syndrome may lead to later age at first birth, linking with infertility. Late age at first birth is associated with parental longevity and reduced incidence of type 2 diabetes and cardiovascular disease. Higher childhood socioeconomic circumstances and those in the highest polygenic score decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, understanding longevity and guiding experimentation into mechanisms of infertility.

Idioma original	English
Páginas (desde-hasta)	1717-1730
Número de páginas	14
Publicación	Nature Human Behaviour
Volumen	5
N.º	12
DOI	https://doi.org/10.1038/s41562-021-01135-3
Estado	Published - dic 2021

Nota bibliográfica

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.

Financiación

A detailed list of funding and other acknowledgements for each cohort can be found in Supplementary Sect. 14. This research was conducted using the UK Biobank resource under application 22276 and 9905. Funding was provided to M.C.M. by the ERC, SOCIOGENOME (615603), CHRONO (835079), ESRC/UKRI SOCGEN (ES/N011856/1), Wellcome Trust ISSF, Leverhulme Trust and Leverhulme Centre for Demographic Science, to N.B. by ERC GENPOP (865356), to F.C.T. by LabEx Ecode, French National Research Agency (ANR) Investissements d’Avenir (ANR-11-LABX-0047), to M.d.H. by Swedish Heart-Lung Foundation (20170872, 20200781, 20140543, 20170678, 20180706 and 20200602), Kjell and Märta Beijer Foundation and Swedish Research Council (2015-03657, 2019-01417). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. This study received ethical approval from the Department of Sociology, University of Oxford, and relevant ethical approval was obtained at the local level for the contributing datasets. The authors thank E. T. Akimova and S. Møllegaard for administrative work in the organization of the cohort information and author list.

Financiadores	Número del financiador
Wellcome Trust ISSF
FP7 Ideas: European Research Council
Leverhulme Trust
CHRONO
LabEx Ecodec ANR
Kjell och Märta Beijers Stiftelse
H2020 European Research Council
Economic and Social Research Council	ES/N011856/1
SOCIOGENOME
ERC GENPOP
UK Industrial Decarbonization Research and Innovation Centre
Horizon 2020 Framework Programme	865356, 835079
Vetenskapsrådet	2015-03657, 2019-01417
Hjärt-Lungfonden	20140543, 20170872, 20200602, 20170678, 20180706, 20200781
French ANR	ANR-11-LABX-0047
European Commission	615603

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

Social Psychology
Experimental and Cognitive Psychology
Behavioral Neuroscience

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10.1038/s41562-021-01135-3

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title = "Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour",

abstract = "Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5–6\% polygenic score prediction. Heritability of age at first birth shifted from 9\% [CI = 4–14\%] for women born in 1940 to 22\% [CI = 19–25\%] for those born in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility and spermatid differentiation. Our findings suggest that polycystic ovarian syndrome may lead to later age at first birth, linking with infertility. Late age at first birth is associated with parental longevity and reduced incidence of type 2 diabetes and cardiovascular disease. Higher childhood socioeconomic circumstances and those in the highest polygenic score decile (90\%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, understanding longevity and guiding experimentation into mechanisms of infertility.",

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Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

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