Udosen, B.; Soremekun, O.; Kamiza, A.; Machipisa, T.; Cheickna, C.; Omotuyi, O.; Soliman, M.; Wélé, M.; Nashiru, O.; Chikowore, T.; Fatumo, S. Meta-Analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits. Int. J. Mol. Sci.2023, 24, 2164.
Udosen, B.; Soremekun, O.; Kamiza, A.; Machipisa, T.; Cheickna, C.; Omotuyi, O.; Soliman, M.; Wélé, M.; Nashiru, O.; Chikowore, T.; Fatumo, S. Meta-Analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits. Int. J. Mol. Sci. 2023, 24, 2164.
Udosen, B.; Soremekun, O.; Kamiza, A.; Machipisa, T.; Cheickna, C.; Omotuyi, O.; Soliman, M.; Wélé, M.; Nashiru, O.; Chikowore, T.; Fatumo, S. Meta-Analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits. Int. J. Mol. Sci.2023, 24, 2164.
Udosen, B.; Soremekun, O.; Kamiza, A.; Machipisa, T.; Cheickna, C.; Omotuyi, O.; Soliman, M.; Wélé, M.; Nashiru, O.; Chikowore, T.; Fatumo, S. Meta-Analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits. Int. J. Mol. Sci. 2023, 24, 2164.
Abstract
Background: High blood pressure (BP) has been implicated as a major risk factor for cardiovascular diseases in several global populations, including in individuals of African ancestry. Despite the elevated burden of high BP-induced cardiovascular diseases in Africa and other global populations with African ancestry, limited genetic studies have been carried out to explore the genetic machinery driving this phenomenon. Methods: We performed univariate and multivariate analyses using Genome-wide association studies (GWAS) and summary statistics data of 77,850 individuals of African ancestry for systolic (SBP) and diastolic blood pressure (DBP) traits. The six independent cohorts used included individuals derived from the African Partnership for Chronic Disease Research (APCDR), the UK Biobank, and the Million Veteran Program (MVP). Subsequently, we annotated, prioritized, visualized, and interpreted our meta-analyses results using FUMA, to gain further insight into the molecular mechanism(s) that contribute to the genetics of BP traits. Finally, loci attaining genome-wide significance, GWS (p<5x10-8) were also followed up with Bayesian fine-mapping to identify potential causal variants. Results: Our meta-analyses altogether identified 350 GWAS SNPs for SBP (166 SNPs) and DBP (184 SNPs, including two novel loci) whilst our multivariate GWAS method identified 166 SNPs (including three novel loci). Interestingly, in FUMA there was significant tissue enrichment of up-regulated differentially expressed genes (DEGs) in the sigmoid and transverse colon for SBP, as well as 10 significant gene sets from MAGMA gene set analyses, However, for DBP, no significant DEGs nor gene sets in MAGMA were found; instead, in DBP for gene property analysis for tissue specificity nine candidates were found to be significant and all nine were in different brain regions. Finally, Bayesian fine-mapping revealed that only 11 variants from the lead SNPs had >50% posterior probability (PP) of being causal and they included novel variant rs562545 (MOBP, PP = 77%) and 10 other previously published variants. Conclusion: Our results demonstrate the importance of performing GWAS in large sample sizes of global populations of African ancestry, including continental Africans; which yield novel insights, from novel loci to novel pathways/tissue expression candidates. Large-scale genomic datasets are required to enhance further discovery and fine-mapping of high-risk loci/variants in highly susceptible groups for cardiovascular disease and other related traits. Our study highlights the need for diversity in genetic research and the importance of expanding large GWASs to include ancestrally diverse populations.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
,
,
,
,
,
*
