Physical and neurobehavioral determinants of reproductive onset and success

Nat Genet. 2016 Jun;48(6):617-623. doi: 10.1038/ng.3551. Epub 2016 Apr 18.


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.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors*
  • Behavior*
  • Cell Adhesion Molecules / genetics
  • Coitus*
  • Estrogen Receptor alpha / genetics
  • Female
  • Genome-Wide Association Study
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Methionine Sulfoxide Reductases / genetics
  • Nerve Tissue Proteins / genetics
  • Puberty
  • RNA-Binding Proteins / genetics
  • Sexual Behavior*
  • Young Adult


  • CADM2 protein, human
  • Cell Adhesion Molecules
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Membrane Proteins
  • Nerve Tissue Proteins
  • RBM6 protein, human
  • RNA-Binding Proteins
  • SEMA3F protein, human
  • Methionine Sulfoxide Reductases
  • methionine sulfoxide reductase