Three Common Variants of LEP, NPY1R and GPR54 Show No Association with Age at Menarche.

Context: Twin and family studies indicate a significant heritability of pubertal timing and more specifically of age at menarche (AAM). Objective: Test the association of AAM with common variants of three candidate genes suspected to have a prominent role in reproductive physiology: leptin (LEP), neuropeptide Y receptor 1 (NPY1R) and GPR54. Design and Methods: We selected the –2459 LEP, the rs7687423 NPY1R and thers350132 GPR54 variants as the more common coding or regulatory variants (minor allelic frequency >0.10) in these gene regions. To avoid stratification problems that can impair association studies, we used the Q-TDT method based on allele transmission to evaluate the relationship of these variants with AAM in 245 healthy women from 107 families of European ancestry. Results: We found no association of AAM with any of the studied variants. Conclusions: Keeping in mind that common variants do not recapitulate the whole genetic variation in a given gene region, this study indicates that the studied LEP, NPY1R and GPR54 variants do not have a major influence upon pubertal timing in Caucasian women. Effects of these genetic loci on age at menarche can definitively be excluded only through determination of extended haplotypes in a larger cohort. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]