%0 Journal Article
%T Dissecting complex traits: recent advances in hypertension genomics
%A Kevin M O'Shaughnessy
%J Genome Medicine
%D 2009
%I BioMed Central
%R 10.1186/gm43
%X The idea that blood pressure (BP) and (by definition) hypertension are polygenic traits arose half a century ago from the famous debate between George Pickering and Robert Platt about the nature of the frequency distribution of BP [1].Many epidemiological studies have subsequently confirmed the heritability of BP; however, its inheritance is not Mendelian as Platt believed, but rather complex. In fact the major diseases of industrialized societies, including obesity, diabetes, and coronary artery disease (CAD), have complex genetics. The favored model for these complex diseases is often referred to as the 'common disease-common variant' hypothesis (CD-CV), in which each susceptibility locus in the human genome for a complex disease is explained by a single (or a handful of) gene variant(s) or allele(s) [2]. This relatively simple allelic architecture, of many susceptibility genes but few variants of each gene, has not been extensively tested. Some loci do fall neatly into this classification, such as the ApoE locus in CAD [3] and PPARG in type 2 diabetes [4], which have single coding variants. However, others, such as the NOD2 locus in Crohn's disease [4] or the calpain 10 (CAPN10) locus in type 2 diabetes [5], cannot be explained so simply. To date, the problem for essential hypertension has been more fundamental, with a difficulty in confidently identifying any susceptibility loci. Linkage-based approaches have been used, but they require family structures that are difficult to recruit in very large numbers. Even when linked loci have been identified [6], there remains the formidable task of finding a functional variant within a locus that perhaps covers a substantial fraction of a chromosome and contains hundreds of genes.In contrast to the difficulties of using linkage, association studies are ideally suited for chasing putative CD-CV gene variants. Initially, association studies explored individual candidate genes, but key genomic discoveries and technological
%U http://genomemedicine.com/content/1/4/43