Interethnic analyses of blood pressure loci in populations of East Asian and European descent

Takeuchi, F.; Akiyama, M.; Matoba, N.; Katsuya, T.; Nakatochi, M.; Tabara, Y.; Narita, A.; Saw, W. -Y.; Moon, S.; Spracklen, C. N.; Chai, J. -F.; Kim, Y. -J.; Zhang, L.; Wang, C.; Li, H.; Li, H.; J. -Y., Wu; Dorajoo, R.; Nierenberg, J. L.; Wang, Y. X.; He, J.; Bennett, D. A.; Takahashi, A.; Momozawa, Y.; Hirata, M.; Matsuda, K.; Rakugi, H.; Nakashima, E.; Isono, M.; Shirota, M.; Hozawa, A.; Ichihara, S.; Matsubara, T.; Yamamoto, K.; Kohara, K.; Igase, M.; Han, S.; Gordon-Larsen, P.; Huang, W.; Lee, N. R.; Adair, L. S.; Hwang, M. Y.; Lee, J.; Chee, M. L.; Sabanayagam, C.; Zhao, W.; Liu, J.; Reilly, D. F.; Sun, L.; Huo, S.; Edwards, T. L.; Long, J.; Chang, L. -C.; Chen, C. -H.; Yuan, J. -M.; Koh, W. -P.; Friedlander, Y.; Kelly, T. N.; Bin Wei, W.; Xu, L.; Cai, H.; Xiang, Y. -B.; Lin, K.; Clarke, R.; Walters, R. G.; Millwood, I. Y.; Li, L.; Chambers, J. C.; Kooner, J. S.; Elliott, P.; van der Harst, P.; Loh, M.; Verweij, N.; Zhang, W.; Lehne, B.; Mateo Leach, I.; Drong, A.; Abbott, J.; Tan, S. -T.; Scott, W. R.; Campanella, G.; Chadeau-Hyam, M.; Afzal, U.; Esko, T.; Harris, S. E.; Hartiala, J.; Kleber, M. E.; Saxena, R.; Stewart, A. F. R.; Ahluwalia, T. S.; Aits, I.; Couto Alves, A. D. S.; Das, S.; Hopewell, J. C.; Koivula, R. W.; Lyytikainen, L. -P.; Postmus, I.; Raitakari, O. T.; Scott, R. A.; Sorice, R.; Tragante, V.; Traglia, M.; White, J.; Barroso, I.; Bjonnes, A.; Collins, R.; Davies, G.; Delgado, G.; Doevendans, P. A.; Franke, L.; Gansevoort, R. T.; Grammer, T. B.; Grarup, N.; Grewal, J.; Hartikainen, A. -L.; Hazen, S. L.; Hsu, C.; Husemoen, L. L. N.; Justesen, J. M.; Kumari, M.; Lieb, W.; Liewald, D. C. M.; Mihailov, E.; Milani, L.; Mills, R.; Mononen, N.; Nikus, K.; Nutile, T.; Parish, S.; Rolandsson, O.; Ruggiero, D.; Sala, C. F.; Snieder, H.; Spaso, T. H. W.; Spiering, W.; Starr, J. M.; Stott, D. J.; Stram, D. O.; Szymczak, S.; Tang, W. H. W.; Trompet, S.; Turjanmaa, V.; Vaarasmaki, M.; van Gilst, W. H.; van Veldhuisen, D. J.; Viikari, J. S.; Asselbergs, F. W.; Ciullo, M.; Franke, A.; Franks, P. W.; Franks, S.; Gross, M. D.; Hansen, T.; Jarvelin, M. -R.; Jorgensen, T.; Jukema, W. J.; Kahonen, M.; Kivimaki, M.; Lehtimaki, T.; Linneberg, A.; Pedersen, O.; Samani, N. J.; Toniolo, D.; Allayee, H.; Deary, I. J.; Marz, W.; Metspalu, A.; Wijmenga, C.; Wolffenbuttel, B. H. W.; Vineis, P.; Kyrtopoulos, S. A.; Kleinjans, J. C. S.; Mccarthy, M. I.; Scott, J.; Chen, Z.; Sasaki, M.; Shu, X. -O.; Jonas, J. B.; He, J.; Heng, C. -K.; Chen, Y. -T.; Zheng, W.; Lin, X.; Teo, Y. -Y.; Tai, E. -S.; Cheng, C. -Y.; Wong, T. Y.; Sim, X.; Mohlke, K. L.; Yamamoto, M.; Kim, B. -J.; Miki, T.; Nabika, T.; Yokota, M.; Kamatani, Y.; Kubo, M.; Kato, N.

doi:10.1038/s41467-018-07345-0

Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.