CONTEXT: 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. DESIGN AND 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.
CONTEXT: 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. DESIGN AND 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: Chunyan He; Peter Kraft; Daniel I Chasman; Julie E Buring; Constance Chen; Susan E Hankinson; Guillaume Paré; Stephen Chanock; Paul M Ridker; David J Hunter Journal: Hum Genet Date: 2010-08-24 Impact factor: 4.132
Authors: Carl A Anderson; Gu Zhu; Mario Falchi; Stéphanie M van den Berg; Susan A Treloar; Timothy D Spector; Nicholas G Martin; Dorret I Boomsma; Peter M Visscher; Grant W Montgomery Journal: J Clin Endocrinol Metab Date: 2008-07-22 Impact factor: 5.958
Authors: Grant W Montgomery; Dale R Nyholt; Zhen Zhen Zhao; Susan A Treloar; Jodie N Painter; Stacey A Missmer; Stephen H Kennedy; Krina T Zondervan Journal: Hum Reprod Update Date: 2008-06-05 Impact factor: 15.610
Authors: Zofia K Z Gajdos; Johannah L Butler; Katherine DeLellis Henderson; Chunyan He; Pamela J Supelak; Matthew Egyud; Alkes Price; David Reich; Peter E Clayton; Loic Le Marchand; David J Hunter; Brian E Henderson; Mark R Palmert; Joel N Hirschhorn Journal: J Clin Endocrinol Metab Date: 2008-08-26 Impact factor: 5.958
Authors: Chunyan He; Peter Kraft; Constance Chen; Julie E Buring; Guillaume Paré; Susan E Hankinson; Stephen J Chanock; Paul M Ridker; David J Hunter; Daniel I Chasman Journal: Nat Genet Date: 2009-05-17 Impact factor: 38.330