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

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509463/
https://www.ncbi.nlm.nih.gov/pubmed/34640315
http://dx.doi.org/10.3390/jcm10194299
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author 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
author_facet 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
author_sort Roa-Díaz, Zayne M.
collection PubMed
description 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.
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spelling pubmed-85094632021-10-13 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 J Clin Med Article 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. MDPI 2021-09-22 /pmc/articles/PMC8509463/ /pubmed/34640315 http://dx.doi.org/10.3390/jcm10194299 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study
title Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study
title_full Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study
title_fullStr Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study
title_full_unstemmed Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study
title_short Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study
title_sort age at natural menopause and blood pressure traits: mendelian randomization study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509463/
https://www.ncbi.nlm.nih.gov/pubmed/34640315
http://dx.doi.org/10.3390/jcm10194299
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