Background: Essential Hypertension (EH) is a global health issue. Despite extensive research, much of EH heritability remains unexplained. We investigated the genetic basis of EH in African-derived individuals from partially isolated quilombo populations in Vale do Ribeira (SP-Brazil).
Methods: Samples from 431 individuals (167 affected, 261 unaffected, 3 unknown) were genotyped using a 650k SNP array. Estimated global ancestry proportions were 47% African, 36% European, and 16% Native American. We constructed six pedigrees using additional data from 673 individuals and created three non-overlapping SNP subpanels. We phased haplotypes and performed local ancestry analysis to account for admixture. Genome-wide linkage analysis (GWLA) and fine-mapping via family-based association studies (FBAS) were conducted, prioritizing EH-associated genes through systematic approach involving databases like PubMed, ClinVar, and GWAS Catalog.
Results: Linkage analysis identified 22 regions of interest (ROIs) with LOD scores ranging 1.45-3.03, encompassing 2363 genes. Fine-mapping (FBAS) identified 60 EH-related candidate genes and 117 suggestive/significant variants. Among these, 14 genes, including PHGDH , S100A10 , MFN2 , and RYR2 , were strongly related to hypertension harboring 29 suggestive/significant SNPs.
Conclusions: Through a complementary approach - combining admixture-adjusted GWLA based on Markov chain Monte Carlo methods, FBAS on known and imputed data, and gene prioritizing - new loci, variants, and candidate genes were identified. These findings provide targets for future research, replication in other populations, facilitate personalized treatments, and improve public health towards African-derived underrepresented populations. Limitations include restricted SNP coverage, self-reported pedigree data, and lack of available EH genomic studies on admixed populations for independent validation, despite the performed genetic correlation analyses using summary statistics.