A Pooled Blood Genome-Wide Association Study of Hypertension in Sindhi Families: Results from the DISFIN Study

Background: Hypertension is an important target for primordial prevention of complex, noncommunicable diseases, and its prevalence remains high across populations. The urban population in India is at a high risk of hypertension, but the genetic basis of hypertension in this population remains poorly understood. Methods: We conducted a pooled whole-blood genome-wide association study of 28 pools representing 1402 participants of the Diabetes In Sindhi Families In Nagpur (DISFIN) study, which enrolled families of probands with type 2 diabetes (T2D). Genotyping was done using Illumina’s Global Screening Array. Results: From a total of 608,550 single-nucleotide variants, 191 were found to be significantly associated with hypertension even after adjusting for metabolic comorbidities, batch effects, pooling error, kinship status, and pooling variation. These variants mapped to 180 well-characterized genes comprising 55 (31%) genes, and encode long noncoding RNAs (lncRNAs). Many of the genes significantly associated with hypertension (including 35% of the lncRNAs) have also been reported by other studies. However, we identified novel genes (SBF2, ARHGAP12, EPAS1, CLEC16A, and LRPPRC) to be associated with hypertension. The most significantly associated lncRNA gene was FLYWCH-AS1. Bioinformatic analyses indicated that these novel genes are likely to have functional importance in hypertension. Conclusions: Our study thus points to the potential candidate genes associated with hypertension in endogamous Sindhi families with T2D patients. The replicable and functional role of these candidate genes should be investigated in future studies.