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


METHODS
Recalled AAM data were collected from 13,697 individuals and 4,899 pseudoindependent sister-pairs from three different populations (Australia, The Netherlands, and the United Kingdom) by mailed questionnaire or interview. Genome-wide variance components linkage analysis was implemented on each sample individually and in combination.


RESULTS
The mean, sd, and heritability of AAM across the three samples was 13.1 yr, 1.5 yr, and 0.69, respectively. No loci were detected that reached genome-wide significance in the combined analysis, but a suggestive locus was detected on chromosome 12 (logarithm of the odds = 2.0). Three loci of suggestive significance were seen in the U.K. sample on chromosomes 1, 4, and 18 (logarithm of the odds = 2.4, 2.2 and 3.2, respectively).


CONCLUSIONS
There was no evidence for common highly penetrant variants influencing AAM. Linkage and association suggest that one trait locus for AAM is located on chromosome 12, but further studies are required to replicate these results.
Anderson
Carl A
CA
Queensland Institute of Medical Research, Royal Brisbane Hospital, Queensland 4029, Australia.
Zhu
Gu
G
Falchi
Mario
M
van den Berg
Stéphanie M
SM
Treloar
Susan A
SA
Spector
Timothy D
TD
Martin
Nicholas G
NG
Boomsma
Dorret I
DI
Visscher
Peter M
PM
Montgomery
Grant W
GW
D000293:Adolescent; D017677:Age Distribution; D001315:Australia; D002648:Child; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D005828:Genetics, Population; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008572:Menarche / Q000208:ethnology / Q000235:genetics* / Q000502:physiology; D009426:Netherlands; D035781:Siblings; D014427:Twins / Q000235:genetics; D006113:United Kingdom; D044465:White People / Q000235:genetics*