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

Kato, N.; Loh, M.; Takeuchi, F.; Verweij, N.; Wang, X.; Zhang, W.; Kelly, T.N.; Saleheen, D.; Lehne, B.; Leach, I.M.; Drong, A.W.; Abbott, J.; Wahl, S.; Tan, S.T.; Scott, W.R.; Campanella, G.; Chadeau-Hyam, M.; Afzal, U.; Ahluwalia, T.S.; Bonder, M.J.; Chen, P.; Dehghan, A.; Edwards, T.L.; Esko, T.; Go, M.J.; Harris, S.E.; Hartiala, J.; Kasela, S.; Kasturiratne, A.; Khor, C.C.; Kleber, M.E.; Li, H.; Mok, Z.Y.; Nakatochi, M.; Sapari, N.S.; Saxena, R.; Stewart, A.F.; Stolk, L.; Tabara, Y.; Teh, A.L.; Wu, Y.; Wu, J.Y.; Zhang, Y.; Aits, I.; Da Silva Couto Alves, A.; Das, S.; Dorajoo, R.; Hopewell, J.C.; Kim, Y.K.; Koivula, R.W.; Luan, J.; Lyytikäinen, L.P.; Nguyen, Q.N.; Pereira, M.A.; Postmus, I.; Raitakari, O.T.; Bryan, M.S.; Scott, R.A.; Sorice, R.; Tragante, V.; Traglia, M.; White, J.; Yamamoto, K.; Zhang, Y.; Adair, L.S.; Ahmed, A.; Akiyama, K.; Asif, R.; Aung, T.; Barroso, I.; Bjonnes, A.; Braun, T.R.; Cai, H.; Chang, L.C.; Chen, C.H.; Cheng, C.Y.; Chong, Y.S.; Collins, R.; Courtney, R.; Davies, G.; Delgado, G.; Do, L.D.; Doevendans, P.A.; Gansevoort, R.T.; Gao, Y.T.; Grammer, T.B.; Grarup, N.; Grewal, J.; Gu, D.; Wander, G.S.; Hartikainen, A.L.; Hazen, S.L.; He, J.; Heng, C.K.; Hixson, J.E.; Hofman, A.; Hsu, C.; Huang, W.; Husemoen, L.L.; Hwang, J.Y.; Ichihara, S.; Igase, M.; Isono, M.; Justesen, J.M.; Katsuya, T.; Kibriya, M.G.; Kim, Y.J.; Kishimoto, M.; Koh, W.P.; Kohara, K.; Kumari, M.; Kwek, K.; Lee, N.R.; Lee, J.; Liao, J.; Lieb, W.; Liewald, D.C.; Matsubara, T.; Matsushita, Y.; Meitinger, T.; Mihailov, E.; Milani, L.; Mills, R.; Mononen, N.; Müller-Nurasyid, M.; Nabika, T.; Nakashima, E.; Ng, H.K.; Nikus, K.; Nutile, T.; Ohkubo, T.; Ohnaka, K.; Parish, S.; Paternoster, L.; Peng, H.; Peters, A.; Pham, S.T.; Pinidiyapathirage, M.J.; Rahman, M.; Rakugi, H.; Rolandsson, O.; Rozario, M.A.; Ruggiero, D.; Sala, C.F.; Sarju, R.; Shimokawa, K.; Snieder, H.; Sparso, T.; Spiering, W.; Starr, J.M.; Stott, D.J.; Stram, D.O.; Sugiyama, T.; Szymczak, S.; Tang, W.H.; Tong, L.; Trompet, S.; Turjanmaa, V.; Ueshima, H.; Uitterlinden, A.G.; Umemura, S.; Vaarasmaki, M.; van Dam, R.M.; van Gilst, W.H.; van Veldhuisen, D.J.; Viikari, J.S.; Waldenberger, M.; Wang, Y.; Wang, A.; Wilson, R.; Wong, T.Y.; Xiang, Y.B.; Yamaguchi, S.; Ye, X.; Young, R.D.; Young, T.L.; Yuan, J.M.; Zhou, X.; Asselbergs, F.W.; Ciullo, M.; Clarke, R.; Deloukas, P.; Franke, A.; Franks, P.W.; Franks, S.; Friedlander, Y.; Gross, M.D.; Guo, Z.; Hansen, T.; Jarvelin, M.R.; Jorgensen, T.; Jukema, J.W.; Kähönen, M.; Kajio, H.; Kivimaki, M.; Lee, J.Y.; Lehtimäki, T.; Linneberg, A.; Miki, T.; Pedersen, O.; Samani, N.J.; Sorensen, T.I.; Takayanagi, R.; Toniolo, D.; BIOS-consortium; CARDIo GRAMplusCD; LifeLines Cohort Study; InterAct Consortium; Ahsan, H.; Allayee, H.; Chen, Y.T.; Danesh, J.; Deary, I.J.; Franco, O.H.; Franke, L.; Heijman, B.T.; Holbrook, J.D.; Isaacs, A.; Kim, B.J.; Lin, X.; Liu, J.; März, W.; Metspalu, A.; Mohlke, K.L.; Sanghera, D.K.; Shu, X.O.; van Meurs, J.B.; Vithana, E.; Wickremasinghe, A.R.; Wijmenga, C.; Wolffenbuttel, B.H.; Yokota, M.; Zheng, W.; Zhu, D.; Vineis, P.; Kyrtopoulos, S.A.; Kleinjans, J.C.; McCarthy, M.I.; Soong, R.; Gieger, C.; Scott, J.; Teo, Y.Y.; He, J.; Elliott, P.; Tai, E.S.; van der Harst, P.; Kooner, J.S.; Chambers, J.C.

dc.contributor.author	Kato, N.
dc.contributor.author	Loh, M.
dc.contributor.author	Takeuchi, F.
dc.contributor.author	Verweij, N.
dc.contributor.author	Wang, X.
dc.contributor.author	Zhang, W.
dc.contributor.author	Kelly, T.N.
dc.contributor.author	Saleheen, D.
dc.contributor.author	Lehne, B.
dc.contributor.author	Leach, I.M.
dc.contributor.author	Drong, A.W.
dc.contributor.author	Abbott, J.
dc.contributor.author	Wahl, S.
dc.contributor.author	Tan, S.T.
dc.contributor.author	Scott, W.R.
dc.contributor.author	Campanella, G.
dc.contributor.author	Chadeau-Hyam, M.
dc.contributor.author	Afzal, U.
dc.contributor.author	Ahluwalia, T.S.
dc.contributor.author	Bonder, M.J.
dc.contributor.author	Chen, P.
dc.contributor.author	Dehghan, A.
dc.contributor.author	Edwards, T.L.
dc.contributor.author	Esko, T.
dc.contributor.author	Go, M.J.
dc.contributor.author	Harris, S.E.
dc.contributor.author	Hartiala, J.
dc.contributor.author	Kasela, S.
dc.contributor.author	Kasturiratne, A.
dc.contributor.author	Khor, C.C.
dc.contributor.author	Kleber, M.E.
dc.contributor.author	Li, H.
dc.contributor.author	Mok, Z.Y.
dc.contributor.author	Nakatochi, M.
dc.contributor.author	Sapari, N.S.
dc.contributor.author	Saxena, R.
dc.contributor.author	Stewart, A.F.
dc.contributor.author	Stolk, L.
dc.contributor.author	Tabara, Y.
dc.contributor.author	Teh, A.L.
dc.contributor.author	Wu, Y.
dc.contributor.author	Wu, J.Y.
dc.contributor.author	Zhang, Y.
dc.contributor.author	Aits, I.
dc.contributor.author	Da Silva Couto Alves, A.
dc.contributor.author	Das, S.
dc.contributor.author	Dorajoo, R.
dc.contributor.author	Hopewell, J.C.
dc.contributor.author	Kim, Y.K.
dc.contributor.author	Koivula, R.W.
dc.contributor.author	Luan, J.
dc.contributor.author	Lyytikäinen, L.P.
dc.contributor.author	Nguyen, Q.N.
dc.contributor.author	Pereira, M.A.
dc.contributor.author	Postmus, I.
dc.contributor.author	Raitakari, O.T.
dc.contributor.author	Bryan, M.S.
dc.contributor.author	Scott, R.A.
dc.contributor.author	Sorice, R.
dc.contributor.author	Tragante, V.
dc.contributor.author	Traglia, M.
dc.contributor.author	White, J.
dc.contributor.author	Yamamoto, K.
dc.contributor.author	Zhang, Y.
dc.contributor.author	Adair, L.S.
dc.contributor.author	Ahmed, A.
dc.contributor.author	Akiyama, K.
dc.contributor.author	Asif, R.
dc.contributor.author	Aung, T.
dc.contributor.author	Barroso, I.
dc.contributor.author	Bjonnes, A.
dc.contributor.author	Braun, T.R.
dc.contributor.author	Cai, H.
dc.contributor.author	Chang, L.C.
dc.contributor.author	Chen, C.H.
dc.contributor.author	Cheng, C.Y.
dc.contributor.author	Chong, Y.S.
dc.contributor.author	Collins, R.
dc.contributor.author	Courtney, R.
dc.contributor.author	Davies, G.
dc.contributor.author	Delgado, G.
dc.contributor.author	Do, L.D.
dc.contributor.author	Doevendans, P.A.
dc.contributor.author	Gansevoort, R.T.
dc.contributor.author	Gao, Y.T.
dc.contributor.author	Grammer, T.B.
dc.contributor.author	Grarup, N.
dc.contributor.author	Grewal, J.
dc.contributor.author	Gu, D.
dc.contributor.author	Wander, G.S.
dc.contributor.author	Hartikainen, A.L.
dc.contributor.author	Hazen, S.L.
dc.contributor.author	He, J.
dc.contributor.author	Heng, C.K.
dc.contributor.author	Hixson, J.E.
dc.contributor.author	Hofman, A.
dc.contributor.author	Hsu, C.
dc.contributor.author	Huang, W.
dc.contributor.author	Husemoen, L.L.
dc.contributor.author	Hwang, J.Y.
dc.contributor.author	Ichihara, S.
dc.contributor.author	Igase, M.
dc.contributor.author	Isono, M.
dc.contributor.author	Justesen, J.M.
dc.contributor.author	Katsuya, T.
dc.contributor.author	Kibriya, M.G.
dc.contributor.author	Kim, Y.J.
dc.contributor.author	Kishimoto, M.
dc.contributor.author	Koh, W.P.
dc.contributor.author	Kohara, K.
dc.contributor.author	Kumari, M.
dc.contributor.author	Kwek, K.
dc.contributor.author	Lee, N.R.
dc.contributor.author	Lee, J.
dc.contributor.author	Liao, J.
dc.contributor.author	Lieb, W.
dc.contributor.author	Liewald, D.C.
dc.contributor.author	Matsubara, T.
dc.contributor.author	Matsushita, Y.
dc.contributor.author	Meitinger, T.
dc.contributor.author	Mihailov, E.
dc.contributor.author	Milani, L.
dc.contributor.author	Mills, R.
dc.contributor.author	Mononen, N.
dc.contributor.author	Müller-Nurasyid, M.
dc.contributor.author	Nabika, T.
dc.contributor.author	Nakashima, E.
dc.contributor.author	Ng, H.K.
dc.contributor.author	Nikus, K.
dc.contributor.author	Nutile, T.
dc.contributor.author	Ohkubo, T.
dc.contributor.author	Ohnaka, K.
dc.contributor.author	Parish, S.
dc.contributor.author	Paternoster, L.
dc.contributor.author	Peng, H.
dc.contributor.author	Peters, A.
dc.contributor.author	Pham, S.T.
dc.contributor.author	Pinidiyapathirage, M.J.
dc.contributor.author	Rahman, M.
dc.contributor.author	Rakugi, H.
dc.contributor.author	Rolandsson, O.
dc.contributor.author	Rozario, M.A.
dc.contributor.author	Ruggiero, D.
dc.contributor.author	Sala, C.F.
dc.contributor.author	Sarju, R.
dc.contributor.author	Shimokawa, K.
dc.contributor.author	Snieder, H.
dc.contributor.author	Sparso, T.
dc.contributor.author	Spiering, W.
dc.contributor.author	Starr, J.M.
dc.contributor.author	Stott, D.J.
dc.contributor.author	Stram, D.O.
dc.contributor.author	Sugiyama, T.
dc.contributor.author	Szymczak, S.
dc.contributor.author	Tang, W.H.
dc.contributor.author	Tong, L.
dc.contributor.author	Trompet, S.
dc.contributor.author	Turjanmaa, V.
dc.contributor.author	Ueshima, H.
dc.contributor.author	Uitterlinden, A.G.
dc.contributor.author	Umemura, S.
dc.contributor.author	Vaarasmaki, M.
dc.contributor.author	van Dam, R.M.
dc.contributor.author	van Gilst, W.H.
dc.contributor.author	van Veldhuisen, D.J.
dc.contributor.author	Viikari, J.S.
dc.contributor.author	Waldenberger, M.
dc.contributor.author	Wang, Y.
dc.contributor.author	Wang, A.
dc.contributor.author	Wilson, R.
dc.contributor.author	Wong, T.Y.
dc.contributor.author	Xiang, Y.B.
dc.contributor.author	Yamaguchi, S.
dc.contributor.author	Ye, X.
dc.contributor.author	Young, R.D.
dc.contributor.author	Young, T.L.
dc.contributor.author	Yuan, J.M.
dc.contributor.author	Zhou, X.
dc.contributor.author	Asselbergs, F.W.
dc.contributor.author	Ciullo, M.
dc.contributor.author	Clarke, R.
dc.contributor.author	Deloukas, P.
dc.contributor.author	Franke, A.
dc.contributor.author	Franks, P.W.
dc.contributor.author	Franks, S.
dc.contributor.author	Friedlander, Y.
dc.contributor.author	Gross, M.D.
dc.contributor.author	Guo, Z.
dc.contributor.author	Hansen, T.
dc.contributor.author	Jarvelin, M.R.
dc.contributor.author	Jorgensen, T.
dc.contributor.author	Jukema, J.W.
dc.contributor.author	Kähönen, M.
dc.contributor.author	Kajio, H.
dc.contributor.author	Kivimaki, M.
dc.contributor.author	Lee, J.Y.
dc.contributor.author	Lehtimäki, T.
dc.contributor.author	Linneberg, A.
dc.contributor.author	Miki, T.
dc.contributor.author	Pedersen, O.
dc.contributor.author	Samani, N.J.
dc.contributor.author	Sorensen, T.I.
dc.contributor.author	Takayanagi, R.
dc.contributor.author	Toniolo, D.
dc.contributor.author	BIOS-consortium
dc.contributor.author	CARDIo GRAMplusCD
dc.contributor.author	LifeLines Cohort Study
dc.contributor.author	InterAct Consortium
dc.contributor.author	Ahsan, H.
dc.contributor.author	Allayee, H.
dc.contributor.author	Chen, Y.T.
dc.contributor.author	Danesh, J.
dc.contributor.author	Deary, I.J.
dc.contributor.author	Franco, O.H.
dc.contributor.author	Franke, L.
dc.contributor.author	Heijman, B.T.
dc.contributor.author	Holbrook, J.D.
dc.contributor.author	Isaacs, A.
dc.contributor.author	Kim, B.J.
dc.contributor.author	Lin, X.
dc.contributor.author	Liu, J.
dc.contributor.author	März, W.
dc.contributor.author	Metspalu, A.
dc.contributor.author	Mohlke, K.L.
dc.contributor.author	Sanghera, D.K.
dc.contributor.author	Shu, X.O.
dc.contributor.author	van Meurs, J.B.
dc.contributor.author	Vithana, E.
dc.contributor.author	Wickremasinghe, A.R.
dc.contributor.author	Wijmenga, C.
dc.contributor.author	Wolffenbuttel, B.H.
dc.contributor.author	Yokota, M.
dc.contributor.author	Zheng, W.
dc.contributor.author	Zhu, D.
dc.contributor.author	Vineis, P.
dc.contributor.author	Kyrtopoulos, S.A.
dc.contributor.author	Kleinjans, J.C.
dc.contributor.author	McCarthy, M.I.
dc.contributor.author	Soong, R.
dc.contributor.author	Gieger, C.
dc.contributor.author	Scott, J.
dc.contributor.author	Teo, Y.Y.
dc.contributor.author	He, J.
dc.contributor.author	Elliott, P.
dc.contributor.author	Tai, E.S.
dc.contributor.author	van der Harst, P.
dc.contributor.author	Kooner, J.S.
dc.contributor.author	Chambers, J.C.
dc.date.accessioned	2015-11-05T10:42:29Z
dc.date.available	2015-11-05T10:42:29Z
dc.date.issued	2015
dc.identifier.citation	Nature Genetics.2015;47:1282 - 1293	en_US
dc.identifier.issn	1061-4036 (Print)
dc.identifier.issn	1546-1718 (Electronic)
dc.identifier.uri	http://repository.kln.ac.lk/handle/123456789/10242
dc.description	Indexed in MEDLINE, SCI, SCI Expanded, BIOSIS Previews	en_US
dc.description.abstract	We carried out a trans-ancestry genome-wide association and replication study of blood pressurephenotypes 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 DNAmethylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNAmethylation 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.	en_US
dc.language.iso	en_US	en_US
dc.publisher	Nature Publishing Company	en_US
dc.subject	genetic loci influencing blood pressure	en_US
dc.title	Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation	en_US
dc.type	Article	en_US

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

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