Abstract
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.
Highlights
Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known
Genome-wide association results in the stage-1 identified 13,003 SNPs with a P value < 1.6×10–5 against any blood pressure phenotype in East Asians. This set of 13,003 SNPs was followed up in 53,008 East Asian individuals. These 13,003 SNPs were examined in the transethnic stage with phenotype-specific results for Europeans from the International Consortium on Blood Pressure (ICBP) Genome-wide association studies (GWASs) (N = 69,909)[3] and the International Genomics of Blood Pressure Consortium (N = 35,344)[10]; there was no overlap in samples between the two data sets
On 10q21 near C10orf[107], a diastolic blood pressure (DBP) association signal was previously reported at rs153044021, which we found to be in linkage disequilibrium (LD) (European LD r2 = 0.48) with an ancestryspecific SNP at the locus, rs4590817, aforementioned (Supplementary Data 7)
Summary
Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. The prevalence of high blood pressure is increased in people of East Asian ancestry, contributing to their increased risk of stroke[9] The reasons for such ethnic differences remain to be clarified from the viewpoint of genetic susceptibility as well as lifestyle. We perform a multi-stage GWAS with a discovery sample of 130,777 East Asian individuals and follow-up meta-analyses involving East Asians and Europeans (max N = 289,038), to seek both transethnic and ancestry-specific genetic effects for five blood pressure phenotypes: systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), mean arterial pressure (MAP), and hypertension. We seek interethnic genetic heterogeneity of GWAS results between East Asians and Europeans, followed by examination of natural selection as a potential mechanism underlying the ethnic differences in genetic susceptibility for blood pressure as well as other complex traits. We report ancestry-specific blood pressure variants and selection signals in this study
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