Ethnic differences in genetic predisposition to hypertension.

Recently, large-scale meta-analyses of genome-wide association (GWA) studies have identified a number of loci significantly associated with systolic and/or diastolic blood pressure (BP). Most of the GWA studies reported to date were conducted in populations of European descent. Given the appreciable ethnic differences in clinical presentation of hypertension, studies in non-European populations allow us to assess the relevance of the findings in Europeans to other ethnic groups and to potentially discover novel variants. Before the GWA scan era, the presence of racial or ethnic differences has been widely recognized for response to antihypertensive therapies, salt sensitivity and impact of obesity on developing hypertension. Despite a limited number of genetic loci that have been proven to show substantial ethnic differences, we can assume four possible genetic mechanisms--(1) absence of target variants in other ethnic groups; (2) presence of allelic heterogeneity; (3) difference in linkage disequilibrium structure; and (4) gene-gene and gene-environment interactions. Considering such a number of potential sources of heterogeneity, we should be cautious about claiming the presence of genuine ethnic differences in genetic susceptibility to BP-related traits or hypertension. Approximately a quarter of BP-associated loci that have been reported in four meta-analyses of GWA studies (i.e., 8 out of 34 loci) appear to be common across three ethnic groups--Europeans, east Asians and south Asians. 'Transethnic' BP meta-analysis will be useful not only for revealing novel susceptibility loci and pathophysiological pathways but also for facilitating the fine mapping of common causal variants.