title: Evaluating GWAS-identified SNPs for age at natural menopause among chinese women.
abstract: BACKGROUND
  Age at natural menopause (ANM) is a complex trait with high heritability and is associated with several major hormonal-related diseases. Recently, several genome-wide association studies (GWAS), conducted exclusively among women of European ancestry, have discovered dozens of genetic loci influencing ANM. No study has been conducted to evaluate whether these findings can be generalized to Chinese women.
  
  
  RESULTS
  We evaluated the index single nucleotide polymorphisms (SNPs) in 19 GWAS-identified genetic susceptibility loci for ANM among 3,533 Chinese women who had natural menopause. We also investigated 3 additional SNPs which were in LD with the index SNP in European-ancestry but not in Asian-ancestry populations. Two genetic risk scores (GRS) were calculated to summarize SNPs across multiple loci one for all SNPs tested (GRSall), and one for SNPs which showed association in our study (GRSsel). All 22 SNPs showed the same association direction as previously reported. Eight SNPs were nominally statistically significant with P≤0.05: rs4246511 (RHBDL2), rs12461110 (NLRP11), rs2307449 (POLG), rs12611091 (BRSK1), rs1172822 (BRSK1), rs365132 (UIMC1), rs2720044 (ASH2L), and rs7246479 (TMEM150B). Especially, SNPs rs4246511, rs365132, rs1172822, and rs7246479 remained significant even after Bonferroni correction. Significant associations were observed for GRS. Women in the highest quartile began menopause 0.7 years (P = 3.24×10(-9)) and 0.9 years (P = 4.61×10(-11)) later than those in the lowest quartile for GRSsel and GRSall, respectively.
  
  
  CONCLUSIONS
  Among the 22 investigated SNPs, eight showed associations with ANM (P<0.05) in our Chinese population. Results from this study extend some recent GWAS findings to the Asian-ancestry population and may guide future efforts to identify genetic determination of menopause.
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Chong
authors.initials: C
authors.lastname: Shen
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Delahanty
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Yong-Bing
authors.initials: YB
authors.lastname: Xiang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.forename: Jirong
authors.initials: J
authors.lastname: Long
mesh_terms: D000367:Age Factors; D044466:Asian People / Q000235:genetics*; D002681:China; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
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