title: Three common variants of LEP, NPY1R and GPR54 show no association with age at menarche.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Pediatric Endocrinology and Institut National de la Santé et de la Recherche Médicale-U561, René Descartes Paris 5 University, Hôpital Saint-Vincent de Paul, Paris, France. anya.rothenbuhler@free.fr
authors.forename: Anya
authors.initials: A
authors.lastname: Rothenbuhler
authors.forename: Chantal
authors.initials: C
authors.lastname: Lotton
authors.forename: Delphine
authors.initials: D
authors.lastname: Fradin
mesh_terms: D000293:Adolescent; D002648:Child; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D020738:Leptin / Q000235:genetics*; D008572:Menarche / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D000074502:Receptors, Kisspeptin-1; D017476:Receptors, Neuropeptide Y / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C118688:KISS1R protein, human; D020738:Leptin; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D017476:Receptors, Neuropeptide Y