Second, as reported previously, 14-17 the strongest association P=9.1×10−14)with schizophrenia is in the extended MHC (chr6:25-34Mb), a region of both exceptional importance and complexity. The MHC comprises 0.3% of the genome but contains 1.5% of the genes in OMIM 42 and 6.4% of genome-wide significant SNP associations in the NHGRI GWAS catalog. 24 It is the second most gene-dense genomic region and has high LD over its extent. We speculate that these features (high gene density and strong LD) combined with the polygenicity of schizophrenia lead to the strong association but will also complicate efforts to identify causal variation. Genome-wide significant associations with schizophrenia extend over 7Mb, but Supplemental Figure 12 suggests that larger samples may resolve this association into sub-regions near TRIM26 (tripartite motif containing 26, chr6:30.1Mb) and the HLA-DRB9 unprocessed pseudogene (chr6:32.4Mb, intergenic HLA-DRA – HLA-DRB5).
