Journal Article

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

Schwander, Karen, Lu, Yingchang, Tao, Ran, Hindorff, Lucia A., Haessler, Jeff, Bielinski, Suzette J., Buyske, Steven, Franceschini, Nora, Fornage, Myriam, Rao, D. C., Kaufman, Joel D., Loos, Ruth J. F., Bien, Stephanie, Guo, Xiuqing, Carlson, Christopher S., Kooperberg, Charles, North, Kari E., Manichaikul, Ani, Carty, Cara L., Zubair, Niha, Rich, Stephen S., Barrett, Paula Q., Ehret, Georg, Bottinger, Erwin P., Sung, Yun Ju, Chakravarti, Aravinda

2016

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: African Americans / Analysis / Biology and Life Sciences / Black or African American - genetics / Blood / Blood pressure / Blood Pressure - genetics / Cancer / Cardiovascular disease / Data processing / Descent / DNA methylation / Endocrine disorders / Epidemiology / Fibroblast growth factor 5 / Gene loci / Gene mapping / Genetic aspects / Genetic Variation / Genetics / Genome-Wide Association Study - methods / Genomes / Genomics / Haplotypes / Health sciences / Hispanic Americans / Hispanic or Latino - genetics / Humans / Hypertension / Loci / Medical research / Medicine and Health Sciences / Meta-analysis / Metabolism / Minority & ethnic groups / Nerve Tissue Proteins - genetics / Obesity / People and Places / Physical Sciences / Population / Population genetics / Population studies / Populations / Potassium / Potassium channels / Potassium Channels, Tandem Pore Domain - genetics / Precision medicine / Pressure variations / Public health / Quantitative Trait Loci / Research and Analysis Methods / Risk analysis / Risk factors / RNA, Long Noncoding - genetics / Studies / Type 2 diabetes