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Identification of 371 Genetic Variants for Age at First Sex and Birth Linked to Externalising Behaviour Publisher Pubmed



Mills MC1, 2 ; Tropf FC1, 2, 3, 4 ; Brazel DM1, 2 ; Van Zuydam N5 ; Vaez A6, 7 ; Pers TH8, 9 ; Snieder H6 ; Perry JRB10 ; Ong KK10 ; Den Hoed M5 ; Barban N11 ; Day FR10
Authors
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Authors Affiliations
  1. 1. Leverhulme Centre for Demographic Science, University of Oxford, Oxford, United Kingdom
  2. 2. Nuffield College, University of Oxford, Oxford, United Kingdom
  3. 3. Ecole Nationale de la Statistique et de L'administration Economique (ENSAE), Paris, France
  4. 4. Center for Research in Economics and Statistics (CREST), Paris, France
  5. 5. Beijer Laboratory and Department of Immunology, Genetics and Pathology, Uppsala University and SciLifeLab, Uppsala, Sweden
  6. 6. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  7. 7. Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran
  8. 8. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  9. 9. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
  10. 10. MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
  11. 11. Department of Statistical Sciences, University of Bologna, Bologna, Italy

Source: Nature human behaviour Published:2021


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