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AGE

, Volume 38, Issue 5–6, pp 513–523 | Cite as

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

  • Jiajun Shi
  • Ben Zhang
  • Ji-Yeob Choi
  • Yu-Tang Gao
  • Huaixing Li
  • Wei Lu
  • Jirong Long
  • Daehee Kang
  • Yong-Bing Xiang
  • Wanqing Wen
  • Sue K. Park
  • Xingwang Ye
  • Dong-Young Noh
  • Ying Zheng
  • Yiqin Wang
  • Seokang Chung
  • Xu Lin
  • Qiuyin Cai
  • Xiao-Ou ShuEmail author
Original Article

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.

Keywords

Menarche Menopause Genome-wide association Single nucleotide polymorphism 

Notes

Acknowledgments

This study was supported, in part, by grants from the US National Institutes of Health (grants R01CA124558, R01CA090899, R01CA070867; R01CA064277 and R01CA092585, R01CA118229, R01CA122756, R01CA137013, R01CA148667), Ingram professorship funds, and Allen Foundation funds at Vanderbilt Epidemiology Center and Division of Epidemiology; SeBCS was supported by the Basic Research Laboratory (BRL) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2011-0001564). NHAPC was supported by research grants including the National Basic Research Program of China (2012CB524905 and 2011CB504002), Knowledge Innovation Program (KSCX2-EW-R-10), the National Natural Science Foundation of China (81321062, 81170734, 81471013, 81200581, 81202272), and the Knowledge Innovation Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (2013KIP107 and 2014KIP107). The authors wish to thank Jing He, Hui Cai, Gong Yang, Jie Wu, and Regina Courtney for their contributions to this project, as well as Nan Kennedy for editing and preparing the manuscript. We also thank the research staff of the Shanghai Breast Cancer Genetics Study, Shanghai Endometrial Cancer Genetics Study, the Shanghai Diabetes Genetics Study, the Shanghai Colorectal Cancer Study, the Nutrition and Health of Aging Population in China study, and the Seoul Breast Cancer Study. In addition, sample preparation and GWAS genotyping assays at Vanderbilt were conducted at the Survey and Biospecimen Shared Resources and the Vanderbilt Microarray Shared Resource, which are supported in part by the Vanderbilt-Ingram Cancer Center (P30CA068485).

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or any other funding agency.

Details of ethics approval

Written informed consent was obtained from all participants, and the study protocols were approved by the institutional review boards of all institutions involved in the study.

Supplementary material

11357_2016_9939_MOESM1_ESM.docx (28 kb)
Table S1 Genome-wide association-identified suggestive SNPs for age at menarche in East Asian women. (DOCX 28 kb)
11357_2016_9939_MOESM2_ESM.docx (28 kb)
Table S2 Genome-wide association-identified suggestive SNPs for age at natural menopause in East Asian women. (DOCX 27 kb)
11357_2016_9939_MOESM3_ESM.docx (179 kb)
Table S3 Evaluation of GWAS-identified single nucleotide polymorphisms for age at menarche in East Asian women. (DOCX 178 KB)

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Copyright information

© American Aging Association 2016

Authors and Affiliations

  • Jiajun Shi
    • 1
  • Ben Zhang
    • 1
  • Ji-Yeob Choi
    • 2
    • 3
    • 4
  • Yu-Tang Gao
    • 5
  • Huaixing Li
    • 6
  • Wei Lu
    • 7
  • Jirong Long
    • 1
  • Daehee Kang
    • 2
    • 3
    • 4
  • Yong-Bing Xiang
    • 5
  • Wanqing Wen
    • 1
  • Sue K. Park
    • 2
    • 3
    • 4
  • Xingwang Ye
    • 6
  • Dong-Young Noh
    • 8
  • Ying Zheng
    • 7
  • Yiqin Wang
    • 6
  • Seokang Chung
    • 2
  • Xu Lin
    • 6
  • Qiuyin Cai
    • 1
  • Xiao-Ou Shu
    • 1
    Email author
  1. 1.Department of Medicine, Vanderbilt Epidemiology Center and Division of EpidemiologyVanderbilt University School of MedicineNashvilleUSA
  2. 2.Department of Biomedical SciencesSeoul National University College of MedicineSeoulKorea
  3. 3.Department of Preventive MedicineSeoul National University College of MedicineSeoulKorea
  4. 4.Cancer Research InstituteSeoul National UniversitySeoulKorea
  5. 5.Department of Epidemiology, Shanghai Cancer Institute, Renji HospitalShanghai Jiaotong University School of MedicineShanghaiChina
  6. 6.Key Laboratory of Nutrition and Metabolism, Institute for Nutritional SciencesShanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of SciencesShanghaiChina
  7. 7.Shanghai Municipal Center for Disease Control and PreventionShanghaiChina
  8. 8.Department of SurgerySeoul National University College of MedicineSeoulKorea

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