Genome-wide copy number variation association analyses for age at menarche.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
Our findings for the first time identified a novel CNV and suggested the DBI-mediated endocrinological pathway as a potential mechanism for AAM regulation.
Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana 70112, USA. yliu8@tulane.edu
Yao-Zhong
YZ
Liu
Jian
J
Li
Rong
R
Pan
Hui
H
Shen
Qing
Q
Tian
Yu
Y
Zhou
Yong-Jun
YJ
Liu
Hong-Wen
HW
Deng
D000293:Adolescent; D002648:Child; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008572:Menarche / Q000235:genetics*; D046228:Microarray Analysis; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics