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

eQTLgen Consortium; BIOS Consortium; Management Team; Cohort collection; Data Generation; Data management and computational infrastructure; Data Analysis Group; Human Reproductive Behaviour Consortium; Lifelines Cohort Study

doi:10.1038/s41562-021-01135-3

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

eQTLgen Consortium
, BIOS Consortium
, Management Team
, Cohort collection
, Data Generation
, Data management and computational infrastructure
, Data Analysis Group
, Human Reproductive Behaviour Consortium
, Lifelines Cohort Study

University of Oxford
École Nationale de la Statistique et de L’administration Économique (ENSAE)
INSEE
Uppsala University
University of Groningen
Isfahan University of Medical Sciences
Ontario Institute for Cancer Research
The University of Chicago
Agency for Science, Technology and Research, Singapore
Leiden University
Johns Hopkins University
Leipzig University
European Molecular Biology Laboratory
Vrije Universiteit Amsterdam
University of Washington
Oncode Institute
Utrecht University
University of Tartu
Massachusetts Institute of Technology
University of Exeter
Georgia Institute of Technology
University of Bristol
Tampere University
University of Helsinki
Icahn School of Medicine at Mount Sinai
University of Lausanne
CIC BioGUNE
Ikerbasque Basque Foundation for Science
University of Queensland
Helmholtz Zentrum München - German Research Center for Environmental Health
Ludwig Maximilian University of Munich
German Centre for Cardiovascular Research
University of Greifswald
Research and Innovation
Garvan Institute of Medical Research
Technical University of Munich
Kaiser Permanente
University of Turku
Maastricht University
Karolinska Institutet
Radboud University Nijmegen
Erasmus University Rotterdam
University of Westminster
Luleå University of Technology
Wenzhou Medical University
Swiss Institute of Bioinformatics
University of Cape Town
University of Colorado Boulder
University of Trieste
Brigham and Women’s Hospital
Harvard University
New York University
Research Institute for Industrial Economics
National Bureau of Economic Research
IRCCS Ospedale Infantile Burlo Garofolo - Trieste
University of Edinburgh
Emory University
University of North Carolina at Chapel Hill
Universidade Federal de Pelotas
University of Kentucky
Adelaide University
South Australian Health And Medical Research Institute
Stockholm School of Economics
University of Cambridge
Queensland Institute of Medical Research
Qatar Foundation HQ
University of Tartu
Boston Children's Hospital
Michigan State University
University of Copenhagen
University College London
deCODE Genetics
Johannes Gutenberg University Mainz
Montpellier Business School
Statens Serum Institut
University of Bologna

Research output: Contribution to journal › Article › peer-review

108 Citations (Scopus)

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
Publication status	Published - Dec 2021
Externally published	Yes

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10.1038/s41562-021-01135-3

Cite this

eQTLgen Consortium, BIOS Consortium, Management Team, Cohort collection, Data Generation, Data management and computational infrastructure, Data Analysis Group, Human Reproductive Behaviour Consortium, & Lifelines Cohort Study (2021). Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour. Nature Human Behaviour, 5(12), 1717-1730. https://doi.org/10.1038/s41562-021-01135-3

@article{d14998086b8046409def269fa06a6718,

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 = "\{eQTLgen Consortium\} and \{BIOS Consortium\} and \{Management Team\} and \{Cohort collection\} and \{Data Generation\} and \{Data management and computational infrastructure\} and \{Data Analysis Group\} and \{Human Reproductive Behaviour Consortium\} and \{Lifelines Cohort Study\} and 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 \{Jan Hottenga\}, Jouke",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = dec,

doi = "10.1038/s41562-021-01135-3",

language = "English",

volume = "5",

pages = "1717--1730",

journal = "Nature Human Behaviour",

issn = "2397-3374",

publisher = "Nature Publishing Group",

number = "12",

}

eQTLgen Consortium, BIOS Consortium, Management Team, Cohort collection, Data Generation, Data management and computational infrastructure, Data Analysis Group, Human Reproductive Behaviour Consortium & Lifelines Cohort Study 2021, 'Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour', Nature Human Behaviour, vol. 5, no. 12, pp. 1717-1730. https://doi.org/10.1038/s41562-021-01135-3

TY - JOUR

T1 - Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour

AU - eQTLgen Consortium

AU - BIOS Consortium

AU - Management Team

AU - Cohort collection

AU - Data Generation

AU - Data management and computational infrastructure

AU - Data Analysis Group

AU - Human Reproductive Behaviour Consortium

AU - Lifelines Cohort Study

AU - Mills, Melinda C.

AU - Tropf, Felix C.

AU - Brazel, David M.

AU - van Zuydam, Natalie

AU - Vaez, Ahmad

AU - Agbessi, Mawussé

AU - Ahsan, Habibul

AU - Alves, Isabel

AU - Andiappan, Anand Kumar

AU - Arindrarto, Wibowo

AU - Awadalla, Philip

AU - Battle, Alexis

AU - Beutner, Frank

AU - Jan Bonder, Marc

AU - Boomsma, Dorret I.

AU - Christiansen, Mark W.

AU - Claringbould, Annique

AU - Deelen, Patrick

AU - Esko, Tõnu

AU - Favé, Marie Julie

AU - Franke, Lude

AU - Frayling, Timothy

AU - Gharib, Sina A.

AU - Gibson, Greg

AU - Heijmans, Bastiaan T.

AU - Hemani, Gibran

AU - Jansen, Rick

AU - Kähönen, Mika

AU - Kalnapenkis, Anette

AU - Kasela, Silva

AU - Kettunen, Johannes

AU - Kim, Yungil

AU - Kirsten, Holger

AU - Kovacs, Peter

AU - Krohn, Knut

AU - Kronberg, Jaanika

AU - Kukushkina, Viktorija

AU - Kutalik, Zoltan

AU - Lee, Bernett

AU - Lehtimäki, Terho

AU - Loeffler, Markus

AU - Marigorta, Urko M.

AU - Mei, Hailang

AU - Milani, Lili

AU - Montgomery, Grant W.

AU - Müller-Nurasyid, Martina

AU - Nauck, Matthias

AU - Nivard, Michel G.

AU - Penninx, Brenda W.J.H.

AU - Jan Hottenga, Jouke

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85117508270

U2 - 10.1038/s41562-021-01135-3

DO - 10.1038/s41562-021-01135-3

M3 - Article

C2 - 34211149

AN - SCOPUS:85117508270

SN - 2397-3374

VL - 5

SP - 1717

EP - 1730

JO - Nature Human Behaviour

JF - Nature Human Behaviour

IS - 12

ER -

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

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