Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study.

Roa-Díaz, Zayne M; Asllanaj, Eralda; Amin, Hasnat A; Rojas, Lyda Z; Nano, Jana; Ikram, Mohammad Arfan; Drenos, Fotios; Franco, Oscar H; Pazoki, Raha; Marques-Vidal, Pedro; Voortman, Trudy; Muka, Taulant (2021). Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study. Journal of clinical medicine, 10(19), p. 4299. MDPI 10.3390/jcm10194299

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Observational studies suggest that early onset of menopause is associated with increased risk of hypertension. Whether this association is causal or due to residual confounding and/or reverse causation remains undetermined. We aimed to evaluate the observational and causal association between age at natural menopause (ANM) and blood pressure traits in Caucasian women. A cross-sectional and one-sample Mendelian randomization (MR) study was conducted in 4451 postmenopausal women from the CoLaus and Rotterdam studies. Regression models were built with observational data to study the associations of ANM with systolic and diastolic blood pressure (SBP/DBP) and hypertension. One-sample MR analysis was performed by calculating a genetic risk score of 54 ANM-related variants, previously identified in a genome-wide association study (GWAS) on ANM. In the two-sample MR analysis we used the estimates from the ANM-GWAS and association estimates from 168,575 women of the UK Biobank to evaluate ANM-related variants and their causal association with SBP and DBP. Pooled analysis from both cohorts showed that a one-year delay in menopause onset was associated with 2% (95% CI 0; 4) increased odds of having hypertension, and that early menopause was associated with lower DBP (β = -1.31, 95% CI -2.43; -0.18). While one-sample MR did not show a causal association between ANM and blood pressure traits, the two-sample MR showed a positive causal association of ANM with SBP; the last was driven by genes related to DNA damage repair. The present study does not support the hypothesis that early onset of menopause is associated with higher blood pressure. Our results suggest different ANM-related genetic pathways could differently impact blood pressure.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)

Graduate School:

Graduate School for Health Sciences (GHS)

UniBE Contributor:

Roa Diaz, Zayne Milena, Franco Duran, Oscar Horacio, Muka, Taulant

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

2077-0383

Publisher:

MDPI

Funders:

[4] Swiss National Science Foundation

Language:

English

Submitter:

Beatrice Minder Wyssmann

Date Deposited:

22 Oct 2021 14:23

Last Modified:

05 Dec 2022 15:53

Publisher DOI:

10.3390/jcm10194299

PubMed ID:

34640315

Additional Information:

Marques-Vidal and Voortman and Muka contributed equially to the manuscript

Uncontrolled Keywords:

age at menopause blood pressure hypertension mendelian randomization analysis menopause systolic blood pressure

BORIS DOI:

10.48350/160279

URI:

https://boris.unibe.ch/id/eprint/160279

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