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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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.

Original language	English
Pages (from-to)	1717-1730
Number of pages	14
Journal	Nature Human Behaviour
Volume	5
Issue number	12
DOIs	https://doi.org/10.1038/s41562-021-01135-3
State	Published - Dec 2021

Bibliographical note

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

Funding

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.

Funders	Funder number
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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Social Psychology
Experimental and Cognitive Psychology
Behavioral Neuroscience

Access to Document

10.1038/s41562-021-01135-3

Cite this

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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.",

author = "Mills, \{Melinda C.\} and Tropf, \{Felix C.\} and Brazel, \{David M.\} and \{van Zuydam\}, Natalie and Ahmad Vaez and Mawuss{\'e} Agbessi and Habibul Ahsan and Isabel Alves and Andiappan, \{Anand Kumar\} and Wibowo Arindrarto and Philip Awadalla and Alexis Battle and Frank Beutner and \{Jan Bonder\}, Marc and Boomsma, \{Dorret I.\} and Christiansen, \{Mark W.\} and Annique Claringbould and Patrick Deelen and T{\~o}nu Esko and Fav{\'e}, \{Marie Julie\} and Lude Franke and Timothy Frayling and Gharib, \{Sina A.\} and Greg Gibson and Heijmans, \{Bastiaan T.\} and Gibran Hemani and Rick Jansen and Mika K{\"a}h{\"o}nen and Anette Kalnapenkis and Silva Kasela and Johannes Kettunen and Yungil Kim and Holger Kirsten and Peter Kovacs and Knut Krohn and Jaanika Kronberg and Viktorija Kukushkina and Zoltan Kutalik and Bernett Lee and Terho Lehtim{\"a}ki and Markus Loeffler and Marigorta, \{Urko M.\} and Hailang Mei and Lili Milani and Montgomery, \{Grant W.\} and Martina M{\"u}ller-Nurasyid and Matthias Nauck and Nivard, \{Michel G.\} and Penninx, \{Brenda W.J.H.\} and Chunyan He",

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AU - Vaez, Ahmad

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AU - Ahsan, Habibul

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AU - Gibson, Greg

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AU - Hemani, Gibran

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AU - Kettunen, Johannes

AU - Kim, Yungil

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AU - Kovacs, Peter

AU - Krohn, Knut

AU - Kronberg, Jaanika

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AU - He, Chunyan

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

Abstract

Bibliographical note

Funding

UN SDGs

ASJC Scopus subject areas

Access to Document

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