Despite having nearly equivalent levels of AD risk variation captured by common genetic markers, EAs and AAs appear to have distinctly different allelic architectures. Genome-wide scores generated from routines that are mismatched for population (i.e., EA COGA discovery sample and AA SAGE target sample, or vice versa) do not predict AD risk (Fig. 1), with R2 values generally less than 0.1% and βs displaying opposite directions of effect (Table S3). This stands in sharp contrast to the genome-wide scoring results reported by Purcell et al. (2009) for a larger sample of schizophrenia subjects, in which AA cases were found to carry significantly more European-derived risk alleles than AA controls (P = 0.008; R2 = 0.4%). Though the aggregate differences in allele frequencies and LD patterns between EAs and AAs are expected to lead to attenuated associations, our findings suggest a larger degree of allelic heterogeneity may exist between these two populations for the genetic liability of AD than for schizophrenia and perhaps other psychiatric disorders.
