Trans-ethnic association study of blood pressure determinants in over 750,000 individuals.
Giri A., Hellwege JN., Keaton JM., Park J., Qiu C., Warren HR., Torstenson ES., Kovesdy CP., Sun YV., Wilson OD., Robinson-Cohen C., Roumie CL., Chung CP., Birdwell KA., Damrauer SM., DuVall SL., Klarin D., Cho K., Wang Y., Evangelou E., Cabrera CP., Wain LV., Shrestha R., Mautz BS., Akwo EA., Sargurupremraj M., Debette S., Boehnke M., Scott LJ., Luan J., Zhao J-H., Willems SM., Thériault S., Shah N., Oldmeadow C., Almgren P., Li-Gao R., Verweij N., Boutin TS., Mangino M., Ntalla I., Feofanova E., Surendran P., Cook JP., Karthikeyan S., Lahrouchi N., Liu C., Sepúlveda N., Richardson TG., Kraja A., Amouyel P., Farrall M., Poulter NR., Understanding Society Scientific Group None., International Consortium for Blood Pressure None., Blood Pressure-International Consortium of Exome Chip Studies None., 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., Harst PVD., Cucca F., Schlessinger D., Hayward C., Spector TD., Jarvelin M-R., Hennig BJ., Timpson NJ., Wei W-Q., Smith JC., Xu Y., Matheny ME., Siew EE., Lindgren C., Herzig K-H., Dedoussis G., Denny JC., Psaty BM., Howson JMM., Munroe PB., Newton-Cheh C., Caulfield MJ., Elliott P., Gaziano JM., Concato J., Wilson PWF., Tsao PS., Velez Edwards DR., Susztak K., Million Veteran Program None., O'Donnell CJ., Hung AM., Edwards TL.
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.