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Age at menarche and age at natural menopause in East Asian women: a genome-wide association study.


ABSTRACT: Age at menarche (AM) and age at natural menopause (ANM) are complex traits with a high heritability. Abnormal timing of menarche or menopause is associated with a reduced span of fertility and risk for several age-related diseases including breast, endometrial and ovarian cancer, cardiovascular disease, and osteoporosis. To identify novel genetic loci for AM or ANM in East Asian women and to replicate previously identified loci primarily in women of European ancestry by genome-wide association studies (GWASs), we conducted a two-stage GWAS. Stage I aimed to discover promising novel AM and ANM loci using GWAS data of 8073 women from Shanghai, China. The Stage II replication study used the data from another Chinese GWAS (n?=?1230 for AM and n?=?1458 for ANM), a Korean GWAS (n?=?4215 for AM and n?=?1739 for ANM), and de novo genotyping of 2877 additional Chinese women. Previous GWAS-identified loci for AM and ANM were also evaluated. We identified two suggestive menarcheal age loci tagged by rs79195475 at 10q21.3 (beta?=?-0.118 years, P?=?3.4?×?10-6) and rs1023935 at 4p15.1 (beta?=?-0.145 years, P?=?4.9?×?10-6) and one menopausal age locus tagged by rs3818134 at 22q12.2 (beta?=?-0.276 years, P?=?8.8?×?10-6). These suggestive loci warrant a further validation in independent populations. Although limited by low statistical power, we replicated 19 of the 98 menarche loci and 5 of the 20 menopause loci previously identified in women of European ancestry in East Asian women, suggesting a shared genetic architecture for these two traits across populations.

SUBMITTER: Shi J 

PROVIDER: S-EPMC5266214 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Age at menarche (AM) and age at natural menopause (ANM) are complex traits with a high heritability. Abnormal timing of menarche or menopause is associated with a reduced span of fertility and risk for several age-related diseases including breast, endometrial and ovarian cancer, cardiovascular disease, and osteoporosis. To identify novel genetic loci for AM or ANM in East Asian women and to replicate previously identified loci primarily in women of European ancestry by genome-wide association s  ...[more]

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