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Metabolic Traits and Stroke Risk in Individuals of African Ancestry: Mendelian Randomization Analysis

BACKGROUND AND PURPOSE: Metabolic traits affect ischemic stroke (IS) risk, but the degree to which this varies across different ethnic ancestries is not known. Our aim was to apply Mendelian randomization to investigate the causal effects of type 2 diabetes (T2D) liability and lipid traits on IS ris...

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Autores principales: Fatumo, Segun, Karhunen, Ville, Chikowore, Tinashe, Sounkou, Toure, Udosen, Brenda, Ezenwa, Chisom, Nakabuye, Mariam, Soremekun, Opeyemi, Daghlas, Iyas, Ryan, David K., Taylor, Amybel, Mason, Amy M., Damrauer, Scott M., Vujkovic, Marijana, Keene, Keith L., Fornage, Myriam, Järvelin, Marjo-Riitta, Burgess, Stephen, Gill, Dipender
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312569/
https://www.ncbi.nlm.nih.gov/pubmed/34078102
http://dx.doi.org/10.1161/STROKEAHA.121.034747
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author Fatumo, Segun
Karhunen, Ville
Chikowore, Tinashe
Sounkou, Toure
Udosen, Brenda
Ezenwa, Chisom
Nakabuye, Mariam
Soremekun, Opeyemi
Daghlas, Iyas
Ryan, David K.
Taylor, Amybel
Mason, Amy M.
Damrauer, Scott M.
Vujkovic, Marijana
Keene, Keith L.
Fornage, Myriam
Järvelin, Marjo-Riitta
Burgess, Stephen
Gill, Dipender
author_facet Fatumo, Segun
Karhunen, Ville
Chikowore, Tinashe
Sounkou, Toure
Udosen, Brenda
Ezenwa, Chisom
Nakabuye, Mariam
Soremekun, Opeyemi
Daghlas, Iyas
Ryan, David K.
Taylor, Amybel
Mason, Amy M.
Damrauer, Scott M.
Vujkovic, Marijana
Keene, Keith L.
Fornage, Myriam
Järvelin, Marjo-Riitta
Burgess, Stephen
Gill, Dipender
author_sort Fatumo, Segun
collection PubMed
description BACKGROUND AND PURPOSE: Metabolic traits affect ischemic stroke (IS) risk, but the degree to which this varies across different ethnic ancestries is not known. Our aim was to apply Mendelian randomization to investigate the causal effects of type 2 diabetes (T2D) liability and lipid traits on IS risk in African ancestry individuals, and to compare them to estimates obtained in European ancestry individuals. METHODS: For African ancestry individuals, genetic proxies for T2D liability and circulating lipids were obtained from a meta-analysis of the African Partnership for Chronic Disease Research study, the UK Biobank, and the Million Veteran Program (total N=77 061). Genetic association estimates for IS risk were obtained from the Consortium of Minority Population Genome-Wide Association Studies of Stroke (3734 cases and 18 317 controls). For European ancestry individuals, genetic proxies for the same metabolic traits were obtained from Million Veteran Program (lipids N=297 626, T2D N=148 726 cases, and 965 732 controls), and genetic association estimates for IS risk were obtained from the MEGASTROKE study (34 217 cases and 406 111 controls). Random-effects inverse-variance weighted Mendelian randomization was used as the main method, complemented with sensitivity analyses more robust to pleiotropy. RESULTS: Higher genetically proxied T2D liability, LDL-C (low-density lipoprotein cholesterol), total cholesterol and lower genetically proxied HDL-C (high-density lipoprotein cholesterol) were associated with increased risk of IS in African ancestry individuals (odds ratio per doubling the odds of T2D liability [95% CI], 1.09 [1.07–1.11]; per standard-deviation increase in LDL-C, 1.12 [1.04–1.21]; total cholesterol: 1.23 [1.06–1.43]; HDL-C, 0.93 [0.89–0.99]). There was no evidence for differences in these estimates when performing analyses in European ancestry individuals. CONCLUSIONS: Our analyses support a causal effect of T2D liability and lipid traits on IS risk in African ancestry individuals, with Mendelian randomization estimates similar to those obtained in European ancestry individuals.
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spelling pubmed-83125692021-08-01 Metabolic Traits and Stroke Risk in Individuals of African Ancestry: Mendelian Randomization Analysis Fatumo, Segun Karhunen, Ville Chikowore, Tinashe Sounkou, Toure Udosen, Brenda Ezenwa, Chisom Nakabuye, Mariam Soremekun, Opeyemi Daghlas, Iyas Ryan, David K. Taylor, Amybel Mason, Amy M. Damrauer, Scott M. Vujkovic, Marijana Keene, Keith L. Fornage, Myriam Järvelin, Marjo-Riitta Burgess, Stephen Gill, Dipender Stroke Brief Reports BACKGROUND AND PURPOSE: Metabolic traits affect ischemic stroke (IS) risk, but the degree to which this varies across different ethnic ancestries is not known. Our aim was to apply Mendelian randomization to investigate the causal effects of type 2 diabetes (T2D) liability and lipid traits on IS risk in African ancestry individuals, and to compare them to estimates obtained in European ancestry individuals. METHODS: For African ancestry individuals, genetic proxies for T2D liability and circulating lipids were obtained from a meta-analysis of the African Partnership for Chronic Disease Research study, the UK Biobank, and the Million Veteran Program (total N=77 061). Genetic association estimates for IS risk were obtained from the Consortium of Minority Population Genome-Wide Association Studies of Stroke (3734 cases and 18 317 controls). For European ancestry individuals, genetic proxies for the same metabolic traits were obtained from Million Veteran Program (lipids N=297 626, T2D N=148 726 cases, and 965 732 controls), and genetic association estimates for IS risk were obtained from the MEGASTROKE study (34 217 cases and 406 111 controls). Random-effects inverse-variance weighted Mendelian randomization was used as the main method, complemented with sensitivity analyses more robust to pleiotropy. RESULTS: Higher genetically proxied T2D liability, LDL-C (low-density lipoprotein cholesterol), total cholesterol and lower genetically proxied HDL-C (high-density lipoprotein cholesterol) were associated with increased risk of IS in African ancestry individuals (odds ratio per doubling the odds of T2D liability [95% CI], 1.09 [1.07–1.11]; per standard-deviation increase in LDL-C, 1.12 [1.04–1.21]; total cholesterol: 1.23 [1.06–1.43]; HDL-C, 0.93 [0.89–0.99]). There was no evidence for differences in these estimates when performing analyses in European ancestry individuals. CONCLUSIONS: Our analyses support a causal effect of T2D liability and lipid traits on IS risk in African ancestry individuals, with Mendelian randomization estimates similar to those obtained in European ancestry individuals. Lippincott Williams & Wilkins 2021-06-03 2021-08 /pmc/articles/PMC8312569/ /pubmed/34078102 http://dx.doi.org/10.1161/STROKEAHA.121.034747 Text en © 2021 The Authors. https://creativecommons.org/licenses/by/4.0/Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
spellingShingle Brief Reports
Fatumo, Segun
Karhunen, Ville
Chikowore, Tinashe
Sounkou, Toure
Udosen, Brenda
Ezenwa, Chisom
Nakabuye, Mariam
Soremekun, Opeyemi
Daghlas, Iyas
Ryan, David K.
Taylor, Amybel
Mason, Amy M.
Damrauer, Scott M.
Vujkovic, Marijana
Keene, Keith L.
Fornage, Myriam
Järvelin, Marjo-Riitta
Burgess, Stephen
Gill, Dipender
Metabolic Traits and Stroke Risk in Individuals of African Ancestry: Mendelian Randomization Analysis
title Metabolic Traits and Stroke Risk in Individuals of African Ancestry: Mendelian Randomization Analysis
title_full Metabolic Traits and Stroke Risk in Individuals of African Ancestry: Mendelian Randomization Analysis
title_fullStr Metabolic Traits and Stroke Risk in Individuals of African Ancestry: Mendelian Randomization Analysis
title_full_unstemmed Metabolic Traits and Stroke Risk in Individuals of African Ancestry: Mendelian Randomization Analysis
title_short Metabolic Traits and Stroke Risk in Individuals of African Ancestry: Mendelian Randomization Analysis
title_sort metabolic traits and stroke risk in individuals of african ancestry: mendelian randomization analysis
topic Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312569/
https://www.ncbi.nlm.nih.gov/pubmed/34078102
http://dx.doi.org/10.1161/STROKEAHA.121.034747
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