Dataset Information

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

ACCESS DATA

Publications

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

Shi Jiajun J Zhang Ben B Choi Ji-Yeob JY Gao Yu-Tang YT Li Huaixing H Lu Wei W Long Jirong J Kang Daehee D Xiang Yong-Bing YB Wen Wanqing W Park Sue K SK Ye Xingwang X Noh Dong-Young DY Zheng Ying Y Wang Yiqin Y Chung Seokang S Lin Xu X Cai Qiuyin Q Shu Xiao-Ou XO

Age (Dordrecht, Netherlands) 20160914 5-6

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]

PMID: 27629107

Similar Datasets

Project description:STUDY QUESTION:Is age at menarche associated with age at menopause or with duration of the reproductive period (interval between menarche and menopause)? SUMMARY ANSWER:The association of age at menarche with age at menopause was weak and non-linear, and the duration of the reproductive period decreased by increasing age at menarche. WHAT IS KNOWN ALREADY:It remains uncertain whether age at menarche is associated with age at menopause. Some studies report that women with early menarche also have early menopause. Other studies report that women with early menarche have late menopause, or they report no association. The duration of the reproductive period may be an indicator of the cumulative endogenous exposure to estrogens and progestogens during life course and is associated with risk of breast cancer and endometrial cancer. STUDY DESIGN, SIZE, DURATION:A retrospective cohort study of 336 788 women, aged 48-71 years, in the BreastScreen Norway during the years 2006-2014 was performed. PARTICIPANTS/MATERIALS, SETTING, METHODS:Information about age at menarche and menopausal status was obtained by self-administered questionnaires. We used time to event approaches to estimate the associations. MAIN RESULTS AND THE ROLE OF CHANCE:Median age at menopause was 51 years in most menarche groups. Women with menarche at age 16 years or age ? 17 years had menopause 1 year later [median: 52 years, interquartile range (IQR): 49-54 years] than women with menarche at age 13 years (median: 51 years, IQR: 49-54 years, reference) (crude hazard ratio (HR) = 0.95; 95% CI: 0.93-0.97 and 0.95; 95% CI: 0.92-0.99, Pnon-linearity < 0.001). The reproductive period decreased with increasing age at menarche (Pnon-linearity < 0.001), and women with menarche at age ? 9 years had 9 years longer median reproductive period than women with menarche at age ? 17 years (median: 43 versus 34 years). Adjustment for year of birth did not change the HR estimates notably. LARGE SCALE DATA:Not applicable. LIMITATIONS, REASONS FOR CAUTION:Information about age at menarche and age at menopause was based on self-reports. Particularly for age at menarche, the long time interval between the event and data collection may have caused imprecise reporting. WIDER IMPLICATIONS OF THE FINDINGS:Our study suggests that age at menarche is a strong indicator for the duration of women's reproductive period. Our findings should encourage studies of the independent role of duration of the reproductive period on the risk of breast cancer and endometrial cancer, since these cancers have been associated with exposure to estrogens and progestogens. STUDY FUNDING/COMPETING INTEREST(S):The present study was funded by the Norwegian Cancer Society [Grant number 6863294-2015]. The authors declare no conflicts of interest.

Project description:BackgroundHormonal reproductive factors have been suggested to play an important role in the etiology of rheumatoid arthritis (RA), an autoimmune inflammatory disorder affecting primarily women. We conducted a two-sample Mendelian randomization (MR) study examining three relevant exposures, age at menarche (AAM), age at natural menopause (ANM), and age at first birth (AFB) with the risk of RA.MethodsWe collected summary statistics from the hitherto largest GWAS conducted in AAM (N = 329,345), ANM (N = 69,360), AFB (N = 251,151), and RA (Ncase = 14,361, Ncontrol = 43,923), all of European ancestry. We constructed strong instruments using hundreds of exposure-associated genetic variants and estimated causal relationship through different MR approaches including an inverse-variance weighted method, an MR-Egger regression and a weighted median method. We conducted a multivariable MR to control for pleiotropic effect acting in particular through obesity and socioeconomic status. We also performed important sensitivity analyses to verify model assumptions.ResultsWe did not find any evidence in support for a causal association between genetically predicted reproductive factors and risk of RA (ORper-SD increment in AAM = 1.06 [0.98-1.15]; ORper-SD increment in ANM = 1.05 [0.98-1.11], OR per-SD increment in AFB = 0.85 [0.65-1.10]). Results remained consistent after removing palindromic SNPs (ORper-SD increment in AAM = 1.06 [0.97-1.15], ORper-SD increment in ANM = 1.05 [0.98-1.13], ORper-SD increment in AFB = 0.81 [0.61-1.07]) or excluding SNPs associated with potential confounding traits (ORper-SD increment in AAM = 1.03 [0.94-1.12], ORper-SD increment in ANM = 1.04 [0.95-1.14]). No outlying instrument was identified through the leave-one-out analysis.ConclusionsOur MR study does not convincingly support a casual effect of reproductive factors, as reflected by age at menarche, age at menopause, and age at first birth, on the development of RA. Despite the largely augmented set of instruments we used, these instruments only explained a modest proportion of phenotypic variance of exposures. Our knowledge regarding this topic is still insufficient and future studies with larger sample size should be designed to replicate or dispute our findings.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets