Genome-wide association study is an approach used in genetics research to look for associations between many (typically hundreds of thousands) of specific genetic variations (most commonly, single-nucleotide polymorphisms) and particular diseases or traits. Similar to genome-wide linkage, the genome-wide association approach interrogates the entire genome, unconstrained by prior assumptions. Genome-wide association studies (GWAS) screen the whole genome at higher resolution levels than genome-wide linkage studies and are capable to narrow down the associated locus more accurately. The genome-wide association approach has effectively replaced genome-wide linkage approach for common disease [17, 22]. Three waves of large-scale high-density genome-wide association studies have led to a series of discoveries in the field of obesity genetics. Recent high-density multistage genome-wide association analyses have so far discovered ~30 loci consistently associated with BMI and obesity-related traits (Table 1). Recent excellent reviews have examined the implications of those loci to the development of human obesity [9, 22, 36]. The strongest signal remains the association with variants within FTO (the fat-mass and obesity-related gene) [37–39] (described in more detail below). Other signals near BDNF, SH2B1, and NEGR1 (all implicated in aspects of neuronal function) reinforce the view of obesity as a disorder of hypothalamic function [36].
