Because the global ancestry information obtained across the whole genome may not reflect the variation of ancestry at the tested genomic locus, methods that adjust the global ancestry to control population stratification may be insufficient. However, methods that conditioned on local ancestry at the tested locus more fully account for the confounding effect of hidden population structure (46). Therefore, we estimated the local ancestry at the NRG1 locus using the HAPMIX program (47), and the overall ancestry across SNPs at the NRG1 locus was included as a covariate in the association analysis to control for the local population stratification, (i.e., the estimated ancestry of the specific genomic region under consideration). Briefly, we downloaded the phased YRI and CEU data from Hapmap Phase II as the parental reference haplotype input for HAPMIX. After QC and filtering the monomorphic SNPs in the phased YRI and CEU data, 188 SNPs that were located at the NRG1 gene and were genotyped in both the SAGE AA sample and in the subset of the replication AA sample (931), were used to estimate local ancestry at
