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 CN., Chai J-F., Kim Y-J., Zhang L., Wang C., Li H., Li H., Wu J-Y., Dorajoo R., Nierenberg JL., Wang YX., He J., Bennett DA., 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 NR., Adair LS., Hwang MY., Lee J., Chee ML., Sabanayagam C., Zhao W., Liu J., Reilly DF., Sun L., Huo S., Edwards TL., Long J., Chang L-C., Chen C-H., Yuan J-M., Koh W-P., Friedlander Y., Kelly TN., Bin Wei W., Xu L., Cai H., Xiang Y-B., Lin K., Clarke R., Walters RG., Millwood IY., Li L., Chambers JC., Kooner JS., Elliott P., van der Harst P., International Genomics of Blood Pressure (iGEN-BP) Consortium None., Chen Z., Sasaki M., Shu X-O., Jonas JB., He J., Heng C-K., Chen Y-T., Zheng W., Lin X., Teo Y-Y., Tai E-S., Cheng C-Y., Wong TY., Sim X., Mohlke KL., Yamamoto M., Kim B-J., Miki T., Nabika T., Yokota M., Kamatani Y., Kubo M., Kato N.
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.