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Association analyses suggest the effects of RANK and RANKL on age at menarche in Chinese women.

ABSTRACT: Age at menarche (AAM), the time of the first menstrual bleeding, is an important developmental milestone in the female life. It marks the beginning of the reproductive period. AAM is implicated in the risk of many health complications in later life. In this study, we conducted an analysis for association of single nucleotide polymorphisms (SNPs) and common haplotypes of two candidate genes, RANK (receptor activator of the NF-?B) and RANKL (receptor activator of the NF-?B ligand), with AAM in 825 unrelated Chinese women.In total, 73 SNPs of RANKL and 23 SNPs of RANK were genotyped. The SNPs and common haplotypes were then analyzed for their association with AAM. Age and age( 2 ) were used as covariates.We found five individual SNPs (rs7239261, rs8094884, rs3826620, rs8089829, and rs9956850) of RANK significantly associated with AAM (p < 0.05). Although no significant association was identified for the RANKL gene, three polymorphisms showed nearly significant (0.05 < p < 0.08) association with AAM. Seven haplotypes of RANK were significantly associated with AAM (p < 0.05); the most significant association of the AT haplotype composed by rs1805034 and rs4524034 (p = 9.4 × 10(-4)) remained significant (p = 0.0235) after the Bonferroni correction for multiple testing. Three haplotypes of RANKL were significantly associated with AAM (p < 0.05). Importantly, the association of rs3826620 replicated our previous findings for Caucasian females.The results of the present study suggest that the RANK and RANKL are two candidate genes for AAM in Chinese women.

SUBMITTER: Pan R

PROVIDER: S-EPMC3682470 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Association analyses suggest the effects of RANK and RANKL on age at menarche in Chinese women.

Pan R R Liu Y-Z YZ Deng H-W HW Dvornyk V V

Climacteric : the journal of the International Menopause Society 20111024 1

<h4>Objectives</h4>Age at menarche (AAM), the time of the first menstrual bleeding, is an important developmental milestone in the female life. It marks the beginning of the reproductive period. AAM is implicated in the risk of many health complications in later life. In this study, we conducted an analysis for association of single nucleotide polymorphisms (SNPs) and common haplotypes of two candidate genes, RANK (receptor activator of the NF-κB) and RANKL (receptor activator of the NF-κB ligan ...[more]

PMID: 22023082

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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

Association analyses suggest the effects of RANK and RANKL on age at menarche in Chinese women.

Publications

Association analyses suggest the effects of RANK and RANKL on age at menarche in Chinese women.

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