Dataset Information

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.

Methodology/principal findings

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.

SUBMITTER: Shen C

PROVIDER: S-EPMC3607593 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Evaluating GWAS-identified SNPs for age at natural menopause among chinese women.

Shen Chong C Delahanty Ryan J RJ Gao Yu-Tang YT Lu Wei W Xiang Yong-Bing YB Zheng Ying Y Cai Qiuyin Q Zheng Wei W Shu Xiao-Ou XO Long Jirong J

PloS one 20130325 3

<h4>Background</h4>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.<h4>Methodology/principal findings</h4>We evaluated the index single nucleo ...[more]

PMID: 23536822

Similar Datasets

Project description:Study questionDo genetic polymorphisms which influence age at menarche in women of European ancestry also influence women of Chinese ancestry?Summary answerMany genetic variants influencing age at menarche in European populations appear to impact Chinese populations in a similar manner.What is known and what this paper addsPrior genome-wide association studies have uncovered 42 SNPs associated with age at menarche in European populations. This study is the first to demonstrate that many of the genetic determinants of age at menarche are shared between European and Chinese women.Participants and settingWe evaluated 37 of 42 SNPs identified as associated with age at menarche from a recent, large meta-analysis, consisting primarily of women of European ancestry, in a population of 6929 Chinese women from Shanghai, China. We also constructed weighted genetic risk scores (GRSs) combining the number of effect variants for all 37 SNPs, or only the SNPs associated with age at menarche among our study population, to evaluate their joint influence on age at menarche.Main resultsFor 32 of the 37 evaluated variants, the direction of the allele associations were the same between women of European ancestry and women of Chinese ancestry (P = 3.71 × 10(-6), binomial sign test); 9 of these were statistically significant. Subjects in the highest quintile of GRSs began menarche ∼5 months later than those in the lowest quintile. BIAS, LIMITATIONS AND GENERALIZABILITY TO OTHER POPULATIONS: Age at menarche was obtained by self-report, which can be subject to recall errors. The current analysis was restricted to loci which met or approached GWAS significance thresholds and did not evaluate loci which may act predominantly or exclusively in the Chinese population. The smaller sample size for our meta-analysis compared with meta-analyses conducted in European populations reduced the power to detect significant results.Study funding/competing interestsThis study was supported, in part, by grants from US National Institutes of Health (grants R01CA124558, R01CA090899, R01CA070867; R01CA064277 and R01CA092585 and UL1 RR024975), Ingram professorship funds and Allen Foundation funds. There are no competing interests to declare.

Dataset Information

Evaluating GWAS-identified SNPs for age at natural menopause among chinese women.

Background

Methodology/principal findings

Conclusions

Publications

Evaluating GWAS-identified SNPs for age at natural menopause among chinese women.

Similar Datasets

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