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medRxiv
MEDRXIV
medRxiv
Cold Spring Harbor Laboratory

38978678
10.1101/2024.06.26.24309531
preprint
3
Article
Genomic Exploration of Essential Hypertension in African-Brazilian Quilombo Populations: A Comprehensive Approach with Pedigree Analysis and Family-Based Association Studies
Borges Vinícius Magalhães http://orcid.org/0000-0002-9502-2549

Horimoto Andrea R.V.R. http://orcid.org/0000-0002-8573-5158

Wijsman Ellen Marie
Kimura Lilian
Nunes Kelly
Nato Alejandro Q. http://orcid.org/0000-0002-8745-9046

Mingroni-Netto Regina Célia
04 9 2024
2024.06.26.24309531https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://medrxiv.org/lookup/doi/10.1101/2024.06.26.24309531
nihpp-2024.06.26.24309531.pdf
ABSTRACT

Background: Essential Hypertension (EH) is a global health issue, responsible for approximately 9.4 million deaths annually. Its prevalence varies by region, with genetic factors contributing 30-60% to blood pressure variation. Despite extensive research, the genetic complexity of EH remains largely unexplained. This study aimed to investigate the genetic basis of EH in African-derived individuals from partially isolated quilombo remnant populations in Vale do Ribeira (SP-Brazil). Methods: Samples from 431 individuals (167 affected, 261 unaffected, 3 with unknown phenotype) were genotyped using a 650k SNP array. Global ancestry proportions were estimated at 47% African, 36% European, and 16% Native American. Additional data from 673 individuals were used to construct six pedigrees. Pedigrees were pruned, and three non-overlapping marker subpanels were created. We phased haplotypes and performed local ancestry analysis to account for admixture. We then conducted genome-wide linkage analysis (GWLA) and performed fine-mapping through family-based association studies (FBAS) on imputed data and through EH-related genes investigation. Results: Linkage analysis identified 22 ROIs with LOD scores ranging from 1.45 to 3.03, encompassing 2363 genes. Fine-mapping identified 60 EH-related candidate genes and 118 suggestive or significant variants (FBAS). Among these, 14 genes, including PHGDH, S100A10, MFN2, and RYR2, were strongly associated with hypertension and harbors 29 SNPs. Conclusions: Through a complementary approach — combining admixture-adjusted genome-wide linkage analysis based on Markov chain Monte Carlo (MCMC) methods, association studies on imputed data, and in silico investigations — genetic regions, variants, and candidate genes were identified, offering insights into the genetic etiology of EH in quilombo remnant populations.
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