Variant Discovery and Fine Mapping of Genetic Loci Associated with Blood Pressure Traits in Hispanics and African Americans

PLoS One. 2016 Oct 13;11(10):e0164132. doi: 10.1371/journal.pone.0164132. eCollection 2016.

Abstract

Despite the substantial burden of hypertension in US minority populations, few genetic studies of blood pressure have been conducted in Hispanics and African Americans, and it is unclear whether many of the established loci identified in European-descent populations contribute to blood pressure variation in non-European descent populations. Using the Metabochip array, we sought to characterize the genetic architecture of previously identified blood pressure loci, and identify novel cardiometabolic variants related to systolic and diastolic blood pressure in a multi-ethnic US population including Hispanics (n = 19,706) and African Americans (n = 18,744). Several known blood pressure loci replicated in African Americans and Hispanics. Fourteen variants in three loci (KCNK3, FGF5, ATXN2-SH2B3) were significantly associated with blood pressure in Hispanics. The most significant diastolic blood pressure variant identified in our analysis, rs2586886/KCNK3 (P = 5.2 x 10-9), also replicated in independent Hispanic and European-descent samples. African American and trans-ethnic meta-analysis data identified novel variants in the FGF5, ULK4 and HOXA-EVX1 loci, which have not been previously associated with blood pressure traits. Our identification and independent replication of variants in KCNK3, a gene implicated in primary hyperaldosteronism, as well as a variant in HOTTIP (HOXA-EVX1) suggest that further work to clarify the roles of these genes may be warranted. Overall, our findings suggest that loci identified in European descent populations also contribute to blood pressure variation in diverse populations including Hispanics and African Americans-populations that are understudied for hypertension genetic risk factors.

MeSH terms

  • African Americans / genetics*
  • Blood Pressure / genetics*
  • Genetic Variation
  • Genome-Wide Association Study / methods*
  • Hispanic Americans / genetics*
  • Humans
  • Nerve Tissue Proteins / genetics
  • Potassium Channels, Tandem Pore Domain / genetics
  • Quantitative Trait Loci*
  • RNA, Long Noncoding / genetics

Substances

  • Nerve Tissue Proteins
  • Potassium Channels, Tandem Pore Domain
  • RNA, Long Noncoding
  • long noncoding RNA HOTTIP, human
  • potassium channel subfamily K member 3