Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

Nat Genet. 2012 Jan 22;44(3):260-8. doi: 10.1038/ng.1051.

Abstract

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

Publication types

  • Meta-Analysis

MeSH terms

  • Age Factors
  • DNA Helicases / genetics
  • DNA Polymerase gamma
  • DNA Primase / genetics
  • DNA Repair / genetics*
  • DNA Repair Enzymes / genetics
  • DNA-Directed DNA Polymerase / genetics
  • European Continental Ancestry Group / genetics
  • Exodeoxyribonucleases / genetics
  • Female
  • Genetic Loci / genetics*
  • Genome-Wide Association Study
  • Humans
  • Immunity / genetics*
  • Menopause / genetics*
  • Menopause / physiology
  • Polymorphism, Single Nucleotide / genetics*
  • Proteins / genetics

Substances

  • Proteins
  • PRRC2A protein, human
  • DNA Primase
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • POLG protein, human
  • EXO1 protein, human
  • Exodeoxyribonucleases
  • DNA Helicases
  • HEL308 protein, human
  • DNA Repair Enzymes

Grant support