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

Autor:	Zhang L; Department of Epidemiology and Health Statistics, School of Public Health, Medical College, the first affiliated hospital of Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College, Soochow University, Suzhou, China.; Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College, Soochow University, Suzhou, China., Wei XT; Department of Epidemiology and Health Statistics, School of Public Health, Medical College, the first affiliated hospital of Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College, Soochow University, Suzhou, China., Niu JJ; Department of Epidemiology and Health Statistics, School of Public Health, Medical College, the first affiliated hospital of Soochow University, Suzhou, China., Lin ZX; Jiangsu Key laboratory of Translational Research and Therapy for Neuropsychiatric disorders & Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, China., Xu Q; Department of Epidemiology and Health Statistics, School of Public Health, Medical College, the first affiliated hospital of Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College, Soochow University, Suzhou, China., Ni JJ; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College, Soochow University, Suzhou, China.; Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College, Soochow University, Suzhou, China., Zhang WL; Department of Epidemiology and Health Statistics, School of Public Health, Medical College, the first affiliated hospital of Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College, Soochow University, Suzhou, China., Han BX; Department of Epidemiology and Health Statistics, School of Public Health, Medical College, the first affiliated hospital of Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College, Soochow University, Suzhou, China., Yan SS; Department of Epidemiology and Health Statistics, School of Public Health, Medical College, the first affiliated hospital of Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College, Soochow University, Suzhou, China., Feng GJ; Department of Epidemiology and Health Statistics, School of Public Health, Medical College, the first affiliated hospital of Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College, Soochow University, Suzhou, China., Zhang H; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College, Soochow University, Suzhou, China.; Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College, Soochow University, Suzhou, China., Yang XL; Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College, Soochow University, Suzhou, China.; Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Jiangsu, Yangzhou, China., Zhang ZJ; Health Commission of Inner Mongolia Autonomous Region, Inner Mongolia Autonomous Region, Hohhot, China., Hai R; Health Commission of Inner Mongolia Autonomous Region, Inner Mongolia Autonomous Region, Hohhot, China., Ren HG; Jiangsu Key laboratory of Translational Research and Therapy for Neuropsychiatric disorders & Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, China., Zhang F; Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China., Pei YF; Department of Epidemiology and Health Statistics, School of Public Health, Medical College, the first affiliated hospital of Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College, Soochow University, Suzhou, China.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2021 Aug 18; Vol. 106 (9), pp. 2574-2591.
DOI:	10.1210/clinem/dgab377
Abstrakt:	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 < 5 × 10-8). No population specificity or heterogeneity was observed at most of the associated loci. Functional annotations prioritized 90 candidate genes at the newly identified loci. Among the 26 traits that were genetically correlated with ANM, hormone replacement therapy (HRT) exerted a causal relationship, implying a causal pattern by which HRT was determined by ANM. Conclusion: Our findings improved our understanding of the etiology of female menopause, as well as shed light on potential new therapies for abnormal menopause. (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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