title: Physical and neurobehavioral determinants of reproductive onset and success.
abstract: The ages of puberty, first sexual intercourse and first birth signify the onset of reproductive ability, behavior and success, respectively. In a genome-wide association study of 125,667 UK Biobank participants, we identify 38 loci associated (P < 5 × 10(-8)) with age at first sexual intercourse. These findings were taken forward in 241,910 men and women from Iceland and 20,187 women from the Women's Genome Health Study. Several of the identified loci also exhibit associations (P < 5 × 10(-8)) with other reproductive and behavioral traits, including age at first birth (variants in or near ESR1 and RBM6-SEMA3F), number of children (CADM2 and ESR1), irritable temperament (MSRA) and risk-taking propensity (CADM2). Mendelian randomization analyses infer causal influences of earlier puberty timing on earlier first sexual intercourse, earlier first birth and lower educational attainment. In turn, likely causal consequences of earlier first sexual intercourse include reproductive, educational, psychiatric and cardiometabolic outcomes.
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, UK.
authors.forename: Felix R
authors.initials: FR
authors.lastname: Day
authors.affiliation: deCODE genetics/Amgen, Reykjavik, Iceland.|School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Hannes
authors.initials: H
authors.lastname: Helgason
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave., East, Boston, MA 02215, USA.|Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave., East, Boston, MA 02215, USA.
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Rose
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Po-Ru
authors.initials: PR
authors.lastname: Loh
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, UK.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Scott
authors.affiliation: deCODE genetics/Amgen, Reykjavik, Iceland.|Department of Anthropology, University of Iceland, Reykjavik, Iceland.
authors.forename: Agnar
authors.initials: A
authors.lastname: Helgason
authors.affiliation: deCODE genetics/Amgen, Reykjavik, Iceland.|School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.affiliation: deCODE genetics/Amgen, Reykjavik, Iceland.
authors.forename: Gisli
authors.initials: G
authors.lastname: Masson
authors.affiliation: deCODE genetics/Amgen, Reykjavik, Iceland.
authors.forename: Olafur Th
authors.initials: OT
authors.lastname: Magnusson
authors.affiliation: deCODE genetics/Amgen, Reykjavik, Iceland.|School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gudbjartsson
authors.affiliation: deCODE genetics/Amgen, Reykjavik, Iceland.|Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave., East, Boston, MA 02215, USA.|Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave., East, Boston, MA 02215, USA.|Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.affiliation: deCODE genetics/Amgen, Reykjavik, Iceland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Sulem
authors.affiliation: deCODE genetics/Amgen, Reykjavik, Iceland.|Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, UK.
authors.forename: Ken K
authors.initials: KK
authors.lastname: Ong
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, UK.
authors.forename: John R B
authors.initials: JRB
authors.lastname: Perry
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001519:Behavior; D015815:Cell Adhesion Molecules / Q000235:genetics; D003075:Coitus; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051150:Methionine Sulfoxide Reductases / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D011627:Puberty; D016601:RNA-Binding Proteins / Q000235:genetics; D012725:Sexual Behavior; D055815:Young Adult
chemical_list: C556123:CADM2 protein, human; D015815:Cell Adhesion Molecules; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C120511:RBM6 protein, human; D016601:RNA-Binding Proteins; C491230:SEMA3F protein, human; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase