Shared Genetics Between Age at Menopause, Early Menopause, POI and Other Traits

Yvonne V. Louwers, Jenny A. Visser*

*Corresponding author for this work

Research output: Contribution to journalReview articleProfessional

16 Citations (Scopus)
99 Downloads (Pure)

Abstract

Reproductive ageing leading to menopause is characterized by depletion of follicles and its regulating mechanisms are only partly understood. Early age at menopause and premature ovarian insufficiency (POI) are associated with several other traits such as cardiovascular disease, dyslipidemia, osteoporosis and diabetes. In large cohorts of Northern European women hundreds of Single Nucleotide Polymorphisms (SNPs) have been identified to be associated with age at menopause. These SNPs are located in genes enriched for immune and mitochondrial function as well as DNA repair and maintenance processes. Genetic predisposition to earlier menopause might also increase the risk of other associated traits. Increased risk for cardiovascular disease in women has been associated with age at menopause lowering SNPs. Pleiotropy between early age at menopause and increased mortality from coronary artery disease has been observed, implicating that genetic variants affecting age at menopause also affect the risk for coronary deaths. This review will discuss the shared genetics of age at menopause with other traits. Mendelian Randomization studies implicate causal genetic association between age at menopause and age at menarche, breast cancer, ovarian cancer, BMD and type 2 diabetes. Although the shared biological pathways remain to be determined, mechanisms that regulate duration of estrogen exposure remain an important focus.

Original languageEnglish
Article number676546
JournalFrontiers in Genetics
Volume12
DOIs
Publication statusPublished - 29 Sept 2021

Bibliographical note

Funding Information:
We would like to thank Professor F. Rivadeneira for his critical comments on our manuscript.

Publisher Copyright:
© Copyright © 2021 Louwers and Visser.

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