Dataset Information

Evaluation of GWAS-identified genetic variants for age at menarche among Chinese women.

ABSTRACT: Do genetic polymorphisms which influence age at menarche in women of European ancestry also influence women of Chinese ancestry?Many genetic variants influencing age at menarche in European populations appear to impact Chinese populations in a similar manner.Prior 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.We 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.For 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.This 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.

SUBMITTER: Delahanty RJ

PROVIDER: S-EPMC3600840 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Evaluation of GWAS-identified genetic variants for age at menarche among Chinese women.

Delahanty R J RJ Beeghly-Fadiel A A Long J R JR Gao Y T YT Lu W W Xiang Y B YB Zheng Y Y Ji B T BT Wen W Q WQ Cai Q Y QY Zheng W W Shu X O XO

Human reproduction (Oxford, England) 20130212 4

<h4>Study question</h4>Do genetic polymorphisms which influence age at menarche in women of European ancestry also influence women of Chinese ancestry?<h4>Summary answer</h4>Many genetic variants influencing age at menarche in European populations appear to impact Chinese populations in a similar manner.<h4>What is known and what this paper adds</h4>Prior genome-wide association studies have uncovered 42 SNPs associated with age at menarche in European populations. This study is the first to dem ...[more]

PMID: 23406970

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Project description:ObjectiveThe occurrence and development of oesophageal neoplasia (ON) is closely related to hormone changes. The aim of this study was to investigate the causal relationships between age at menarche (AAMA) or age at menopause (AAMO) and benign oesophageal neoplasia (BON) or malignant oesophageal neoplasia (MON) from a genetic perspective.MethodsGenome-wide association study (GWAS) summary data of exposures (AAMA and AAMO) and outcomes (BON and MON) were obtained from the IEU OpenGWAS database. We performed a two-sample Mendelian randomization (MR) study between them. The inverse variance weighted (IVW) was used as the main analysis method, while the MR Egger, weighted median, simple mode, and weighted mode were supplementary methods. The maximum likelihood, penalized weighted median, and IVW (fixed effects) were validation methods. We used Cochran's Q statistic and Rucker's Q statistic to detect heterogeneity. The intercept test of the MR Egger and global test of MR pleiotropy residual sum and outlier (MR-PRESSO) were used to detect horizontal pleiotropy, and the distortion test of the MR-PRESSO analysis was used to detect outliers. The leave-one-out analysis was used to detect whether the MR analysis was affected by single nucleotide polymorphisms (SNPs). In addition, the MR robust adjusted profile score (MR-RAPS) method was used to assess the robustness of MR analysis.ResultsThe random-effects IVW results showed that AAMA had a negative genetic causal relationship with BON (odds ratio [OR] = 0.285 [95% confidence interval [CI]: 0.130-0.623], P = 0.002). The weighted median, maximum likelihood, penalized weighted median, and IVW (fixed effects) were consistent with random-effects IVW (P < 0.05). The MR Egger, simple mode and weighted mode results showed that AAMA had no genetic causal relationship with BON (P > 0.05). However, there were no causal genetic relationships between AAMA and MON (OR = 1.132 [95%CI: 0.621-2.063], P = 0.685), AAMO and BON (OR = 0.989 [95%CI: 0.755-1.296], P = 0.935), or AAMO and MON (OR = 1.129 [95%CI: 0.938-1.359], P = 0.200). The MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and IVW (fixed effects) were consistent with a random-effects IVW (P > 0.05). MR analysis results showed no heterogeneity, the horizontal pleiotropy and outliers (P > 0.05). They were not driven by a single SNP, and were normally distributed (P > 0.05).ConclusionOnly AAMA has a negative genetic causal relationship with BON, and no genetic causal relationships exist between AAMA and MON, AAMO and BON, or AAMO and MON. However, it cannot be ruled out that they are related at other levels besides genetics.

Dataset Information

Evaluation of GWAS-identified genetic variants for age at menarche among Chinese women.

Publications

Evaluation of GWAS-identified genetic variants for age at menarche among Chinese women.

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