Although the concept of GWAS was initially proposed in 1996, 119 no GWAS was conducted until 2005. 120 Since then, this technique became the preferred mapping tool for complex diseases/traits.32 As of October 2015, nine published GWASs and meta-GWASs have yielded 11 genetic loci carrying variants of genome-wide significance (GWS; p < 5×10−8) associated with relevant ND phenotypes in subjects of European, African, and East Asian ancestries (Table 3 and Figure 1). However, only three loci were replicated in more than two independent GWASs or meta-GWASs, among which the CHRNA5/A3/B4 gene cluster has the most evidence of significance.
