Results
Title

Joint Genome-Wide Association Analyses Identified 49 Novel Loci For Age at Natural Menopause.

Authors

Lei Zhang; Xin-Tong Wei; Jun-Jie Niu; Zi-Xuan Lin; Qian Xu; Jing-Jing Ni; Wan-Lin Zhang; Bai-Xue Han; Shan-Shan Yan; Gui-Juan Feng; Hong Zhang; Xiao-Lin Yang; Zi-Jia Zhang; Rong Hai; Hai-Gang Ren; Feng Zhang; Yu-Fang Pei; Zhang, Lei; Wei, Xin-Tong; Niu, Jun-Jie

Abstract

Background: Age at natural menopause (ANM) is an important index for women's health. Either early or late ANM is associated with a series of adverse outcomes later in life. Despite being an inheritable trait, its genetic determinant has not yet been fully understood.Methods: Aiming to better characterize the genetic architecture of ANM, we conducted genome-wide association study (GWAS) meta-analyses in European-specific as well as trans-ancestry samples by using GWAS summary statistics from the following 3 large studies: the Reproductive Genetics Consortium (ReproGen; N = 69 626), the UK Biobank cohort (UKBB; N = 111 593) and the BioBank Japan Project (BBJ; N = 43 861), followed by a series of bioinformatical assessments and functional annotations.Results: By integrating the summary statistics from the 3 GWAS of up to 225 200 participants, this largest meta-analysis identified 49 novel loci and 3 secondary signals that were associated with ANM at the genome-wide significance level (P Conclusion: Our findings improved our understanding of the etiology of female menopause, as well as shed light on potential new therapies for abnormal menopause.

Subjects

GENOME-wide association studies; GENETIC variation; MENOPAUSE; MEDICAL research; GENETIC epidemiology; BREAST; HERITABILITY; PROGESTERONE receptors; THERAPEUTICS; RESEARCH; SEQUENCE analysis; GENETICS; HORMONES; META-analysis; AGE distribution; RESEARCH methodology; GENETIC polymorphisms; MEDICAL cooperation; EVALUATION research; CELLULAR signal transduction; COMPARATIVE studies; GENOMES; RESEARCH funding

Publication

Journal of Clinical Endocrinology & Metabolism, 2021, Vol 106, Issue 9, p2574

ISSN

0021-972X

Publication type

Academic Journal

DOI

10.1210/clinem/dgab377