A genome-wide linkage scan for age at menarche in three populations of European descent

Context: Age at menarche (AAM) is an important trait both biologically and socially, a clearly defined event in female pubertal development, and has been associated with many clinically significant phenotypes. Objective: The objective of the study was to identify genetic loci influencing variation in AAM in large population-based samples from three countries. Design/Participants: RecalledAAMdatawere collected from13,697 individuals and 4,899 pseudo-independent sister-pairs from three different populations (Australia, The Netherlands, and the United Kingdom) by mailed questionnaire or interview. Genome-wide variance components link-age analysis was implemented on each sample individually and in combination. Results: Themean, SD, andheritability ofAAMacross the three sampleswas 13.1 yr, 1.5 yr, and 0.69, respectively. No loci were detected that reached genome-wide significance in the combined anal-ysis, but a suggestive locus was detected on chromosome 12 (logarithm of the odds 2.0). Three loci of suggestive significancewere seen in theU.K. sampleon chromosomes1, 4, and18 (logarithm of the odds 2.4, 2.2 and 3.2, respectively). Conclusions: Therewasnoevidence for commonhighlypenetrant variants influencingAAM. Linkag