CONTEXT: Menarche is a significant physiological event for women. Age at menarche (AAM) is a heritable trait associated with many common female diseases. The genetic basis and the mechanism for AAM are largely unknown. Copy number variation (CNV) is a common type of genetic variation underlying human complex traits. The importance of CNV to AAM variation is unclear. OBJECTIVE: The objective of the study was to identify CNV important to AAM variation. DESIGN: We performed the first genome-wide CNV study of AAM in 1654 Caucasian females using Affymetrix human single-nucleotide polymorphism 6.0 array. We also replicated our findings in another Chinese cohort containing 752 women. RESULTS: We identified a CNV, variation_38399, in the 2q14.2 region, for association with AAM (P = 1.03 × 10(-3)). The CNV has two variants (one copy and two copy), with a mean AAM of 14.00 yr and 12.90 yr, respectively. Interestingly, in a Chinese sample containing 752 women, this CNV has been replicated both with a marginally significant P = 0.090 and with a same direction of effect (a lower copy number for a later AAM). The CNV is located approximately 75 kb upstream of the diazepam binding inhibitor (DBI), a gene known to regulate estrogen levels, a key factor for menarche. CONCLUSION: Our findings for the first time identified a novel CNV and suggested the DBI-mediated endocrinological pathway as a potential mechanism for AAM regulation.
CONTEXT: Menarche is a significant physiological event for women. Age at menarche (AAM) is a heritable trait associated with many common female diseases. The genetic basis and the mechanism for AAM are largely unknown. Copy number variation (CNV) is a common type of genetic variation underlying human complex traits. The importance of CNV to AAM variation is unclear. OBJECTIVE: The objective of the study was to identify CNV important to AAM variation. DESIGN: We performed the first genome-wide CNV study of AAM in 1654 Caucasian females using Affymetrix humansingle-nucleotide polymorphism 6.0 array. We also replicated our findings in another Chinese cohort containing 752 women. RESULTS: We identified a CNV, variation_38399, in the 2q14.2 region, for association with AAM (P = 1.03 × 10(-3)). The CNV has two variants (one copy and two copy), with a mean AAM of 14.00 yr and 12.90 yr, respectively. Interestingly, in a Chinese sample containing 752 women, this CNV has been replicated both with a marginally significant P = 0.090 and with a same direction of effect (a lower copy number for a later AAM). The CNV is located approximately 75 kb upstream of the diazepam binding inhibitor (DBI), a gene known to regulate estrogen levels, a key factor for menarche. CONCLUSION: Our findings for the first time identified a novel CNV and suggested the DBI-mediated endocrinological pathway as a potential mechanism for AAM regulation.
Authors: Anthony F Jorm; Helen Christensen; Bryan Rodgers; Patricia A Jacomb; Simon Easteal Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2004-02-15 Impact factor: 3.568
Authors: J-R Long; H Xu; L-J Zhao; P-Y Liu; H Shen; Y-J Liu; D-H Xiong; P Xiao; Y-Z Liu; V Dvornyk; J-L Li; R R Recker; H-W Deng Journal: J Med Genet Date: 2005-10 Impact factor: 6.318
Authors: Steven A McCarroll; Tracy N Hadnott; George H Perry; Pardis C Sabeti; Michael C Zody; Jeffrey C Barrett; Stephanie Dallaire; Stacey B Gabriel; Charles Lee; Mark J Daly; David M Altshuler Journal: Nat Genet Date: 2006-01 Impact factor: 38.330