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Meta-Analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits

High blood pressure (HBP) has been implicated as a major risk factor for cardiovascular diseases in several populations, including individuals of African ancestry. Despite the elevated burden of HBP-induced cardiovascular diseases in Africa and other populations of African descent, limited genetic s...

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Autores principales: Udosen, Brenda, Soremekun, Opeyemi, Kamiza, Abram, Machipisa, Tafadzwa, Cheickna, Cisse, Omotuyi, Olaposi, Soliman, Mahmoud, Wélé, Mamadou, Nashiru, Oyekanmi, Chikowore, Tinashe, Fatumo, Segun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916484/
https://www.ncbi.nlm.nih.gov/pubmed/36768488
http://dx.doi.org/10.3390/ijms24032164
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author Udosen, Brenda
Soremekun, Opeyemi
Kamiza, Abram
Machipisa, Tafadzwa
Cheickna, Cisse
Omotuyi, Olaposi
Soliman, Mahmoud
Wélé, Mamadou
Nashiru, Oyekanmi
Chikowore, Tinashe
Fatumo, Segun
author_facet Udosen, Brenda
Soremekun, Opeyemi
Kamiza, Abram
Machipisa, Tafadzwa
Cheickna, Cisse
Omotuyi, Olaposi
Soliman, Mahmoud
Wélé, Mamadou
Nashiru, Oyekanmi
Chikowore, Tinashe
Fatumo, Segun
author_sort Udosen, Brenda
collection PubMed
description High blood pressure (HBP) has been implicated as a major risk factor for cardiovascular diseases in several populations, including individuals of African ancestry. Despite the elevated burden of HBP-induced cardiovascular diseases in Africa and other populations of African descent, limited genetic studies have been carried out to explore the genetic mechanism driving this phenomenon. We performed genome-wide association univariate and multivariate analyses of both systolic (SBP) and diastolic blood pressure (DBP) traits in 77, 850 individuals of African ancestry. We used summary statistics data from six independent cohorts, including the African Partnership for Chronic Disease Research (APCDR), the UK Biobank, and the Million Veteran Program (MVP). FUMA was used to annotate, prioritize, visualize, and interpret our findings to gain a better understanding of the molecular mechanism(s) underlying the genetics of BP traits. Finally, we undertook a Bayesian fine-mapping analysis to identify potential causal variants. Our meta-analysis identified 10 independent variants associated with SBP and 9 with DBP traits. Whilst our multivariate GWAS method identified 21 independent signals, 18 of these SNPs have been previously identified. SBP was linked to gene sets involved in biological processes such as synapse assembly and cell–cell adhesion via plasma membrane adhesion. Of the 19 independent SNPs identified in the BP meta-analysis, only 11 variants had posterior probability (PP) of > 50%, including one novel variant: rs562545 (MOBP, PP = 77%). To facilitate further research and fine-mapping of high-risk loci/variants in highly susceptible groups for cardiovascular disease and other related traits, large-scale genomic datasets are needed. Our findings highlight the importance of including ancestrally diverse populations in large GWASs and the need for diversity in genetic research.
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spelling pubmed-99164842023-02-11 Meta-Analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits Udosen, Brenda Soremekun, Opeyemi Kamiza, Abram Machipisa, Tafadzwa Cheickna, Cisse Omotuyi, Olaposi Soliman, Mahmoud Wélé, Mamadou Nashiru, Oyekanmi Chikowore, Tinashe Fatumo, Segun Int J Mol Sci Article High blood pressure (HBP) has been implicated as a major risk factor for cardiovascular diseases in several populations, including individuals of African ancestry. Despite the elevated burden of HBP-induced cardiovascular diseases in Africa and other populations of African descent, limited genetic studies have been carried out to explore the genetic mechanism driving this phenomenon. We performed genome-wide association univariate and multivariate analyses of both systolic (SBP) and diastolic blood pressure (DBP) traits in 77, 850 individuals of African ancestry. We used summary statistics data from six independent cohorts, including the African Partnership for Chronic Disease Research (APCDR), the UK Biobank, and the Million Veteran Program (MVP). FUMA was used to annotate, prioritize, visualize, and interpret our findings to gain a better understanding of the molecular mechanism(s) underlying the genetics of BP traits. Finally, we undertook a Bayesian fine-mapping analysis to identify potential causal variants. Our meta-analysis identified 10 independent variants associated with SBP and 9 with DBP traits. Whilst our multivariate GWAS method identified 21 independent signals, 18 of these SNPs have been previously identified. SBP was linked to gene sets involved in biological processes such as synapse assembly and cell–cell adhesion via plasma membrane adhesion. Of the 19 independent SNPs identified in the BP meta-analysis, only 11 variants had posterior probability (PP) of > 50%, including one novel variant: rs562545 (MOBP, PP = 77%). To facilitate further research and fine-mapping of high-risk loci/variants in highly susceptible groups for cardiovascular disease and other related traits, large-scale genomic datasets are needed. Our findings highlight the importance of including ancestrally diverse populations in large GWASs and the need for diversity in genetic research. MDPI 2023-01-21 /pmc/articles/PMC9916484/ /pubmed/36768488 http://dx.doi.org/10.3390/ijms24032164 Text en © 2023 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
Udosen, Brenda
Soremekun, Opeyemi
Kamiza, Abram
Machipisa, Tafadzwa
Cheickna, Cisse
Omotuyi, Olaposi
Soliman, Mahmoud
Wélé, Mamadou
Nashiru, Oyekanmi
Chikowore, Tinashe
Fatumo, Segun
Meta-Analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits
title Meta-Analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits
title_full Meta-Analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits
title_fullStr Meta-Analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits
title_full_unstemmed Meta-Analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits
title_short Meta-Analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits
title_sort meta-analysis and multivariate gwas analyses in 77,850 individuals of african ancestry identify novel variants associated with blood pressure traits
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916484/
https://www.ncbi.nlm.nih.gov/pubmed/36768488
http://dx.doi.org/10.3390/ijms24032164
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