Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension

Abstract

Hypertension is a common disorder and the leading risk factor for cardiovascular disease and premature deaths worldwide. Genome-wide association studies (GWASs) in the European population have identified multiple chromosomal regions associated with blood pressure, and the identified loci altogether explain only a small fraction of the variance for blood pressure. The differences in environmental exposures and genetic background between Chinese and European populations might suggest potential different pathways of blood pressure regulation. To identify novel genetic variants affecting blood pressure variation, we conducted a meta-analysis of GWASs of blood pressure and hypertension in 11 816 subjects followed by replication studies including 69 146 additional individuals. We identified genome-wide significant (P < 5.0 × 10(-8)) associations with blood pressure, which included variants at three new loci (CACNA1D, CYP21A2, and MED13L) and a newly discovered variant near SLC4A7. We also replicated 14 previously reported loci, 8 (CASZ1, MOV10, FGF5, CYP17A1, SOX6, ATP2B1, ALDH2, and JAG1) at genome-wide significance, and 6 (FIGN, ULK4, GUCY1A3, HFE, TBX3-TBX5, and TBX3) at a suggestive level of P = 1.81 × 10(-3) to 5.16 × 10(-8). These findings provide new mechanistic insights into the regulation of blood pressure and potential targets for treatments.

Figure 1.

Regional association plots of blood pressure and hypertension loci. (A–E) Results are shown for rs820430 (A), rs9810888 (B), rs9266359 (C), rs2021783 (D) and rs11067763 (E). In the top panel of each, SNPs are plotted according to their chromosomal positions (NCBI build36) with their P-values (as −log₁₀ P-values) of the discovery meta-analysis. The lead SNP is represented by a purple diamond. The r² values of LD between the lead SNP and the other SNPs are indicated by different colors. The estimated recombination rates from 1000 Genomes June 2010 CHB + JPT samples are plotted in cyan to reflect the local LD structure. The bottom panels illustrate the locations of known genes.

Figure 2.

Cumulative effects of risk alleles on blood pressure levels. This figure shows blood pressure levels as a solid dot with whiskers extending to ±1 S.E. across the risk score categories. The gray bars represent the number of individuals in each risk score category.