title: Weight-adjusted genome scan analysis for mapping quantitative trait Loci for menarchal age.
abstract: BACKGROUND
  Twin and family studies indicate that genetic factors contribute to the variability of age at menarche (AAM), a multifactorial trait of major importance to human reproductive success. Individual variability of premenarcheal fatness is known to be an important determinant of AAM.
  
  
  OBJECTIVE
  The objective of the study was mapping quantitative trait loci (QTLs) for AAM.
  
  
  METHODS
  AAM was assessed in 98 sister pairs of recent European ancestry whose growth charts were available. There was a negative correlation between menarcheal body weight sd score (SDS) and AAM (r = 0.47, P < 0.0001). We designed a genome scan approach and used the variance components model implemented in Merlin for quantitative traits to evaluate linkage of AAM and AAM adjusted for menarcheal weight SDS to 418 genome-wide microsatellites.
  
  
  RESULTS
  Multipoint linkage analysis for AAM revealed nominal QTLs defined by LOD scores between 1.06 and 1.69 on chromosomes 1p, 1q, 7p, 8q, 16p, 19q, and 20q. The genome scan for AAM adjusted for menarcheal weight SDS revealed several QTLs with strongly suggestive LOD scores in 16q21 (LOD = 3.33), 16q12 (LOD = 3.12), and 8p12 (LOD = 2.18) and a number of other nominally significant QTLs yet viewed as hypothetical.
  
  
  CONCLUSIONS
  We found several regions that may contain determinants of AAM, but there is still a long series of steps to confirm these QTLs and identify the genomic polymorphisms implicated in AAM variability.
authors.affiliation: Department of Pediatric Endocrinology and U56, Institut National de la Santé et de la Recherche Médicale, Hôpital Saint-Vincent de Paul, 75014 Paris, France.
authors.forename: Anya
authors.initials: A
authors.lastname: Rothenbuhler
authors.forename: Delphine
authors.initials: D
authors.lastname: Fradin
authors.forename: Simon
authors.initials: S
authors.lastname: Heath
authors.forename: Hervé
authors.initials: H
authors.lastname: Lefevre
authors.forename: Claire
authors.initials: C
authors.lastname: Bouvattier
authors.forename: Marc
authors.initials: M
authors.lastname: Lathrop
authors.forename: Pierre
authors.initials: P
authors.lastname: Bougnères
mesh_terms: D000367:Age Factors; D001835:Body Weight; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D008126:Lod Score; D008572:Menarche / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*; D035781:Siblings
chemical_list: D004247:DNA