In this paper we investigate the polygenic architecture of alcoholism by evaluating the extent to which common, genome-wide SNPs collectively capture the variation in susceptibility in two US populations, European-Americans (EAs) and African-Americans (AAs). To achieve this, we aggregated genotypic data from case-control samples into sets of quantitative scores, representing varying thresholds of GWAS P-values or particular classes of minor allele frequency (MAF), and tested their association to AD, as well as their fit to simulated disease models. In addition, we computed empirical, additive genetic relationships between case-control subjects with the available GWAS data and estimated from them the total variance in AD liability that is accounted by common SNPs via linear mixed models, as proposed by Yang and colleagues (2010). Lastly, in an effort to identify some of the specific genetic mechanisms that underlie the biology of AD, the designated scoring bins of putative risk alleles were annotated to gene locations and tested for gene enrichment for various biological ontologies and signaling pathways in EA and AA populations using a permuted approach.
