TY - JOUR
T1 - Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour
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 - Stehouwer, Coen D.A.
AU - van Greevenbroek, Marleen
AU - van der Kallen, Carla
AU - Schalkwijk, Casper
AU - eQTLgen Consortium
AU - BIOS Consortium
AU - Cohort collection
AU - Data Generation
AU - Data management and computational infrastructure
AU - Data Analysis Group
AU - Human Reproductive Behaviour Consortium
N1 - Funding Information:
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.
Funding Information:
The main authors declare no competing interests. The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. M.I.M. has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo Nordisk and Eli Lilly and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier and Takeda. As of June 2019, M.I.M. is an employee of Genentech and a holder of Roche stock.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/12/1
Y1 - 2021/12/1
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.
U2 - 10.1038/s41562-021-01135-3
DO - 10.1038/s41562-021-01135-3
M3 - Article
SN - 2397-3374
VL - 5
SP - 1717
EP - 1730
JO - Nature human behaviour
JF - Nature human behaviour
IS - 12
ER -