title: 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.
authors.affiliation: Department of Medicine, Vanderbilt Epidemiology Center and Division of Epidemiology, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 600, IMPH, Nashville, Tennessee, 37203, USA.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Medicine, Vanderbilt Epidemiology Center and Division of Epidemiology, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 600, IMPH, Nashville, Tennessee, 37203, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.|Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.|Cancer Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Ji-Yeob
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Huaixing
authors.initials: H
authors.lastname: Li
authors.affiliation: Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Medicine, Vanderbilt Epidemiology Center and Division of Epidemiology, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 600, IMPH, Nashville, Tennessee, 37203, USA.
authors.forename: Jirong
authors.initials: J
authors.lastname: Long
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.|Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.|Cancer Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.affiliation: Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yong-Bing
authors.initials: YB
authors.lastname: Xiang
authors.affiliation: Department of Medicine, Vanderbilt Epidemiology Center and Division of Epidemiology, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 600, IMPH, Nashville, Tennessee, 37203, USA.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Wen
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.|Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.|Cancer Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Sue K
authors.initials: SK
authors.lastname: Park
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xingwang
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.affiliation: Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seokang
authors.initials: S
authors.lastname: Chung
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Medicine, Vanderbilt Epidemiology Center and Division of Epidemiology, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 600, IMPH, Nashville, Tennessee, 37203, USA.
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Department of Medicine, Vanderbilt Epidemiology Center and Division of Epidemiology, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 600, IMPH, Nashville, Tennessee, 37203, USA. xiao-ou.shu@vanderbilt.edu.
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
mesh_terms: D000367:Age Factors; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002681:China; D015331:Cohort Studies; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007723:Korea; D016014:Linear Models; D008572:Menarche / Q000208:ethnology / Q000235:genetics*; D008593:Menopause / Q000208:ethnology / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
keywords: Genome-wide association; Menarche; Menopause; Single nucleotide polymorphism