The most strongly associated SNPs (Table 4) do not identify genes from physiological systems previously implicated by clinical or genetic studies in hypertension. The strongest signal overall is with rs2820037 on 1q43 (genotypic test, P=7.7×10-7). The closest genes are RYR2 (encoding the ryanodine receptor 2), mutations in which are associated with stress-induced polymorphic ventricular tachycardia and arrhythmogenic right ventricular dysplasia80,81; CHRM3, encoding the cholinergic receptor muscarinic 3, a member of the G protein-coupled receptor family32; and ZP4, the product of which is zona pellucida glycoprotein 481. The strong association signals on the X chromosome using an expanded reference group (see below and Supplementary Table 9) are of substantial interest but they do not identify known genes of obvious relevance to HT.
