Trans-ethnic association study of blood pressure determinants in over 750,000 individuals.
Nature genetics 2018 ; 51: 51-62.
Giri A, Hellwege JN, Warren HR, Kovesdy CP, Sun YV, Robinson-Cohen C, Damrauer SM, Klarin D, Wang Y, Evangelou E, Cabrera CP, Wain LV, Sargurupremraj M, Debette S, Boehnke M, Scott LJ, Luan J, Zhao JH, Willems S, Thériault S, Shah N, Oldmeadow C, Almgren P, Li-Gao R, Verweij N, Boutin TS, Mangino M, Ntalla I, Surendran P, Cook JP, Karthikeyan S, Amouyel P, Farrall M, Poulter NR, Laakso M, Zeggini E, Sever P, Scott RA, Langenberg C, Wareham NJ, Conen D, Palmer CNA, Attia J, Chasman DI, Ridker PM, Melander O, Mook-Kanamori DO, Cucca F, Schlessinger D, Hayward C, Spector TD, Järvelin MR, Hennig BJ, Timpson NJ, Lindgren C, Herzig KH, Dedoussis G, Denny JC, Psaty BM, Howson JMM, Munroe PB, Newton-Cheh C, Caulfield MJ, Elliott P, Gaziano JM, Wilson PWF, Tsao PS, Velez Edwards DR, Susztak K, O'Donnell CJ, Hung AM, Edwards TL
DOI : 10.1038/s41588-018-0303-9
PubMed ID : 30578418
PMCID : PMC6365102
Abstract
In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program (MVP) and collaborating studies, with analysis of the blood pressure clinical phenome in MVP. Our transcriptome-wide association study detected 4,043 blood pressure associations with genetically predicted gene expression of 840 genes in 45 tissues, and mouse renal single-cell RNA sequencing identified upregulated blood pressure genes in kidney tubule cells.