title: Familial concordance for age at natural menopause: results from the Breakthrough Generations Study.
abstract: OBJECTIVE
  Existing estimates of the heritability of menopause age have a wide range. Furthermore, few studies have analyzed to what extent familial similarities might reflect shared environment, rather than shared genes. We therefore analyzed familial concordance for age at natural menopause and the effects of shared genetic and environmental factors on this concordance.
  
  
  METHODS
  Participants were 2,060 individuals comprising first-degree relatives, aged 31 to 90 years, and participating in the UK Breakthrough Generations Study. Menopause data were collected using a self-administered questionnaire and analyzed using logistic regression and variance-components models.
  
  
  RESULTS
  Women were at an increased risk of early menopause (≤45 y) if their mother (odds ratio, 6.2; P < 0.001) or non-twin sister (odds ratio, 5.5; P < 0.001) had had an early menopause. Likewise, women had an increased risk of late menopause (≥54 y) if their relative had had a late menopause (mother: odds ratio, 6.1; P < 0.01; non-twin sister: odds ratio, 2.3; P < 0.001). Estimated heritability was 41.6% (P < 0.01), with an additional 13.6% (P = 0.02) of the variation in menopause age attributed to environmental factors shared by sisters.
  
  
  CONCLUSIONS
  We confirm that early menopause aggregates within families and show, for the first time, that there is also strong familial concordance for late menopause. Both genes and shared environment were the source of variation in menopause age. Past heritability estimates have not accounted for shared environment, and thus, the effect of genetic variants on menopause age may previously have been overestimated.
authors.affiliation: Section of Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK. Danielle.Morris@icr.ac.uk
authors.forename: Danielle H
authors.initials: DH
authors.lastname: Morris
authors.forename: Michael E
authors.initials: ME
authors.lastname: Jones
authors.forename: Minouk J
authors.initials: MJ
authors.lastname: Schoemaker
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Swerdlow
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005190:Family; D005260:Female; D006801:Humans; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D011795:Surveys and Questionnaires; D014427:Twins / Q000235:genetics; D006113:United Kingdom / Q000453:epidemiology