For a given threshold τ, we calculated two GRMs based on SNPs in the genic and intergenic regions, and then fitted an LMM to estimate how much variance could be explained by these two parts. The results are shown in the right panel of Figure 3. For τ = 0 kb, the genic region, composed of 48% of all SNPs, explained only about 9.5% (s.e. 11.9%) of the phenotypic variance, while the intergenic region, composed of 52% of SNPs, explained 14.5% (s.e. 12.2%) of the phenotypic variance. As the threshold increased to 10 kb, the variance explained by the genic region quickly increased to 14.9% (s.e. 11.7%). After that, the variance explained by the genic region increased slowly. When the threshold increased to 20 kb, the explained variance increased to 17.5% (s.e. 11.4%). For the intergenic region, the explained variance dropped quickly when the threshold increased to 20 kb and then remained almost the same. These findings indicate that most AD-associated common genetic variants are likely to be distributed within 10-20 kb of a gene.
