ABSTRACT
The completion of the human genome sequence in 2005 and its derivative, the HapMap Project, together with rapid improvements in genotyping analysis, have allowed a genome-wide scan of genes for complex traits or diseases (Altshuler, Daly, and Lander 2008; Ikram et al. 2009; Psychiatric GCCC 2009). Such genome-wide association studies (GWAS) have greatly stimulated our hope that detailed genetic control mechanisms for complex phenotypes can be understood at individual nucleotide levels or nucleotide combinations. In the past several years, more than 250 loci have been reproducibly identified for polygenic traits (Hirschhorn 2009). It is impressive that many genes detected affect the outcome of a trait or disease through its biochemical and metabolic pathways. For example, of the 23 loci detected for lipid levels, 11 trigger their effects by encoding apolipoproteins, lipases, and other key proteins in lipid biosynthesis (Mohlke, Boehnke, and Abecasis 2008). Genes associated with Crohn’s disease encode autophagy and interleukin-23 related pathways (Lettre and Rioux 2008). The height loci detected regulate directly chromatin proteins and hedgehog signaling (Hirschhorn and Lettre 2009). GWAS have also identified genes that encode action sites of drugs approved by the U.S. Food and Drug Administration, including thiazolidinediones and sulfonylureas (in studies of type 2 diabetes; Mohlke, Boehnke, and Abecasis 2008), statins (lipid levels; Mohlke, Boehnke, and Abecasis 2008), and estrogens (bone density; Styrkarsdottir et al. 2009).
