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 - eQTLGen Consortium
AU - BIOS Consortium
AU - Human Reproductive Behaviour Consortium
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 - Perola, Markus
AU - Pervjakova, Natalia
AU - Pierce, Brandon L.
AU - Powell, Joseph
AU - Prokisch, Holger
AU - Psaty, Bruce M.
AU - Raitakari, Olli T.
AU - Ripatti, Samuli
AU - Rotzschke, Olaf
AU - Rüeger, Sina
AU - Saha, Ashis
AU - Scholz, Markus
AU - Schramm, Katharina
AU - Seppälä, Ilkka
AU - Slagboom, Eline P.
AU - Stehouwer, Coen D.A.
AU - Stumvoll, Michael
AU - Sullivan, Patrick
AU - ‘t Hoen, Peter A.C.
AU - Teumer, Alexander
AU - Thiery, Joachim
AU - Tong, Lin
AU - Tönjes, Anke
AU - van Dongen, Jenny
AU - van Iterson, Maarten
AU - van Meurs, Joyce
AU - Veldink, Jan H.
AU - Verlouw, Joost
AU - Visscher, Peter M.
AU - Völker, Uwe
AU - Võsa, Urmo
AU - Westra, Harm Jan
AU - Wijmenga, Cisca
AU - Yaghootkar, Hanieh
AU - Yang, Jian
AU - Zeng, Biao
AU - Zhang, Futao
AU - van Greevenbroek, Marleen M.J.
AU - Schalkwijk, Casper G.
AU - Deelen, Joris
AU - van Heemst, Diana
AU - van Duijn, Cornelia M.
AU - Hofman, Bert A.
AU - Isaacs, Aaron
AU - Uitterlinden, André G.
AU - Verbiest, Michael
AU - Suchiman, H. Eka D.
AU - Verkerk, Marijn
AU - van der Breggen, Ruud
AU - van Rooij, Jeroen
AU - Lakenberg, Nico
AU - Mei, Hailiang
AU - Bot, Jan
AU - Zhernakova, Dasha V.
AU - Luijk, René
AU - Bonder, Marc Jan
AU - Swertz, Morris A.
AU - van Zwet, Erik W.
AU - Akimova, Evelina T.
AU - Bergmann, Sven
AU - Boardman, Jason D.
AU - Buring, Julie E.
AU - Cesarini, David
AU - Chasman, Daniel I.
AU - Chavarro, Jorge E.
AU - Cocca, Massimiliano
AU - Concas, Maria Pina
AU - Davey-Smith, George
AU - Davies, Gail
AU - Deary, Ian J.
AU - Gaskins, Audrey J.
AU - de Geus, Eco J.C.
AU - Gieger, Christian
AU - Girotto, Giorgia
AU - Grabe, Hans Jörgen
AU - Gunderson, Erica P.
AU - Harris, Kathleen Mullan
AU - Hartwig, Fernando P.
AU - He, Chunyan
AU - Homuth, Georg
AU - Horta, Bernando Lessa
AU - Jan Hottenga, Jouke
AU - Huang, Hongyang
AU - Hyppӧnen, Elina
AU - Ikram, M. Arfan
AU - Johannesson, Magnus
AU - Kamali, Zoha
AU - Kavousi, Maryam
AU - Kraft, Peter
AU - Kühnel, Brigitte
AU - Langenberg, Claudia
AU - Study, Lifelines Cohort
AU - Lind, Penelope A.
AU - Luan, Jian’an
AU - Mägi, Reedik
AU - Magnusson, Patrik K.E.
AU - Mahajan, Anubha
AU - Martin, Nicholas G.
AU - Mbarek, Hamdi
AU - McCarthy, Mark I.
AU - McMahon, George
AU - McQueen, Matthew B.
AU - Medland, Sarah E.
AU - Meitinger, Thomas
AU - Metspalu, Andres
AU - Mihailov, Evelin
AU - Missmer, Stacey A.
AU - Møllegaard, Stine
AU - Mook-Kanamori, Dennis O.
AU - Morgan, Anna
AU - van der Most, Peter J.
AU - de Mutsert, Renée
AU - Noordam, Raymond
AU - Power, Chris
AU - Redmond, Paul
AU - Rich-Edwards, Janet W.
AU - Ridker, Paul M.
AU - Rietveld, Cornelius A.
AU - Ring, Susan M.
AU - Rose, Lynda M.
AU - Rueedi, Rico
AU - Stefánsson, Kári
AU - Stöckl, Doris
AU - Strauch, Konstantin
AU - Thurik, A. Roy
AU - Timpson, Nicholas J.
AU - Turman, Constance
AU - Wareham, Nicholas J.
AU - Willemsen, Gonneke
AU - Zhao, Jing Hau
AU - Pers, Tune H.
AU - Snieder, Harold
AU - Perry, John R.B.
AU - Ong, Ken K.
AU - den Hoed, Marcel
AU - Barban, Nicola
AU - Day, Felix R.
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).
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.
KW - Genome-wide association studies
KW - behavioural genetics
KW - demography
KW - fertility
UR - https://www.ebi.ac.uk/gwas/search?query=34211149
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 -