Genome-wide association studies of age at menarche and age at natural menopause

Mol Cell Endocrinol. 2014 Jan 25;382(1):767-779. doi: 10.1016/j.mce.2012.05.003. Epub 2012 May 14.


Genome-wide association studies (GWAS) have been successful in uncovering genetic determinants of age at menarche and age at natural menopause. To date, more than 30 novel genetic loci have been identified in GWAS for age at menarche and 17 for age at natural menopause. These findings have stimulated a plethora of follow-up studies particularly with respect to the functional characterization of these novel loci and how these results can be translated into risk prediction. However, the genetic loci identified so far account for only a small fraction of the overall heritability. This review provides an overview of the current state of our knowledge of the genetic basis of menarche and menopause timing. It emphasizes recent GWAS results and outlines strategies for discovering the missing heritability and strategies to further our understanding of the underlying molecular mechanisms of the observed genetic associations.

Keywords: Age at menarche; Age at natural menopause; Candidate gene association studies; Genome-wide association studies; Linkage analysis.

Publication types

  • Review

MeSH terms

  • Age Factors
  • Aging / genetics*
  • Female
  • Genetic Linkage
  • Genome-Wide Association Study*
  • Humans
  • Menarche / genetics*
  • Menopause / genetics*