Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.

Published

Journal Article

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

Full Text

Duke Authors

Cited Authors

  • Kato, N; Loh, M; Takeuchi, F; Verweij, N; Wang, X; Zhang, W; Kelly, TN; Saleheen, D; Lehne, B; Leach, IM; Drong, AW; Abbott, J; Wahl, S; Tan, S-T; Scott, WR; Campanella, G; Chadeau-Hyam, M; Afzal, U; Ahluwalia, TS; Bonder, MJ; Chen, P; Dehghan, A; Edwards, TL; Esko, T; Go, MJ; Harris, SE; Hartiala, J; Kasela, S; Kasturiratne, A; Khor, C-C; Kleber, ME; Li, H; Yu Mok, Z; Nakatochi, M; Sapari, NS; Saxena, R; Stewart, AFR; Stolk, L; Tabara, Y; Teh, AL; Wu, Y; Wu, J-Y; Zhang, Y; Aits, I; Da Silva Couto Alves, A; Das, S; Dorajoo, R; Hopewell, JC; Kim, YK; Koivula, RW; Luan, J; Lyytikäinen, L-P; Nguyen, QN; Pereira, MA; Postmus, I; Raitakari, OT; Scannell Bryan, M; Scott, RA; Sorice, R; Tragante, V; Traglia, M; White, J; Yamamoto, K; Zhang, Y; Adair, LS; Ahmed, A; Akiyama, K; Asif, R; Aung, T; Barroso, I; Bjonnes, A; Braun, TR; Cai, H; Chang, L-C; Chen, C-H; Cheng, C-Y; Chong, Y-S; Collins, R; Courtney, R; Davies, G; Delgado, G; Do, LD; Doevendans, PA; Gansevoort, RT; Gao, Y-T; Grammer, TB; Grarup, N; Grewal, J; Gu, D; Wander, GS; Hartikainen, A-L; Hazen, SL; He, J; Heng, C-K; Hixson, JE; Hofman, A; Hsu, C; Huang, W; Husemoen, LLN; Hwang, J-Y; Ichihara, S; Igase, M; Isono, M; Justesen, JM; Katsuya, T; Kibriya, MG; Kim, YJ; Kishimoto, M; Koh, W-P; Kohara, K; Kumari, M; Kwek, K; Lee, NR; Lee, J; Liao, J; Lieb, W; Liewald, DCM; Matsubara, T; Matsushita, Y; Meitinger, T; Mihailov, E; Milani, L; Mills, R; Mononen, N; Müller-Nurasyid, M; Nabika, T; Nakashima, E; Ng, HK; Nikus, K; Nutile, T; Ohkubo, T; Ohnaka, K; Parish, S; Paternoster, L; Peng, H; Peters, A; Pham, ST; Pinidiyapathirage, MJ; Rahman, M; Rakugi, H; Rolandsson, O; Ann Rozario, M; Ruggiero, D; Sala, CF; Sarju, R; Shimokawa, K; Snieder, H; Sparsø, T; Spiering, W; Starr, JM; Stott, DJ; Stram, DO; Sugiyama, T; Szymczak, S; Tang, WHW; Tong, L; Trompet, S; Turjanmaa, V; Ueshima, H; Uitterlinden, AG; Umemura, S; Vaarasmaki, M; van Dam, RM; van Gilst, WH; van Veldhuisen, DJ; Viikari, JS; Waldenberger, M; Wang, Y; Wang, A; Wilson, R; Wong, T-Y; Xiang, Y-B; Yamaguchi, S; Ye, X; Young, RD; Young, TL; Yuan, J-M; Zhou, X; Asselbergs, FW; Ciullo, M; Clarke, R; Deloukas, P; Franke, A; Franks, PW; Franks, S; Friedlander, Y; Gross, MD; Guo, Z; Hansen, T; Jarvelin, M-R; Jørgensen, T; Jukema, JW; Kähönen, M; Kajio, H; Kivimaki, M; Lee, J-Y; Lehtimäki, T; Linneberg, A; Miki, T; Pedersen, O; Samani, NJ; Sørensen, TIA; Takayanagi, R; Toniolo, D; BIOS-consortium, ; CARDIo GRAMplusCD, ; LifeLines Cohort Study, ; InterAct Consortium, ; Ahsan, H; Allayee, H; Chen, Y-T; Danesh, J; Deary, IJ; Franco, OH; Franke, L; Heijman, BT; Holbrook, JD; Isaacs, A; Kim, B-J; Lin, X; Liu, J; März, W; Metspalu, A; Mohlke, KL; Sanghera, DK; Shu, X-O; van Meurs, JBJ; Vithana, E; Wickremasinghe, AR; Wijmenga, C; Wolffenbuttel, BHW; Yokota, M; Zheng, W; Zhu, D; Vineis, P; Kyrtopoulos, SA; Kleinjans, JCS; McCarthy, MI; Soong, R; Gieger, C; Scott, J; Teo, Y-Y; He, J; Elliott, P; Tai, ES; van der Harst, P; Kooner, JS; Chambers, JC

Published Date

  • November 2015

Published In

Volume / Issue

  • 47 / 11

Start / End Page

  • 1282 - 1293

PubMed ID

  • 26390057

Pubmed Central ID

  • 26390057

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/ng.3405

Language

  • eng

Conference Location

  • United States