GWASs are a potentially more powerful alternative to linkage for locating genes without prior knowledge of physiology or disease pathophysiology. GWAS designs are unique in their potential to identify risk loci of relatively small effect (without prior hypothesis), much smaller than may be detected through linkage strategies. Further, linkage requires family sampling schemes, which create a bias towards detection of loci of relatively high attributable risk ratios; other loci may, however, be more important on a population level. The first GWAS for a specific SD trait (excluding studies that used a pooling methodology exclusively) examined ND (Bierut et al. 2007). A two-stage design was employed; first a study using pooled DNA was used to screen 2.4 million SNPs; second, >30,000 SNPs selected from the first stage were screened individually in 1,050 cases and 879 controls. Numerous genes were identified as possibly associated to ND, including both novel genes (e.g., neurexin 1, NRXN1, and vacuolar protein sorting 13 homolog A, VPS13A) and genes that were previously considered candidates based on known physiology (e.g., cholinergic receptor, nicotinic, alpha 5, CHRNA5). The latter
