In addition to pathway enrichment, the collective network approach elevates the importance of ANK3, DGKH and ODZ4 for BD susceptibility in the WTCCC GWAS, despite their weak single-locus effect in the data.
Individuals at high familial risk for BD homozygous for the DGKH risk haplotype demonstrated relatively greater activation (poor suppression) of these regions during the task vs the low-risk haplotype subjects.
A modest association was also detected for SNP rs1012053 (GWAS P = 4.50 × 10(-2)) in DGKH, which has already been reported as the most significant variant in a previous genome-wide scan on bipolar disorder.
Cross-disorder analysis of bipolar risk genes: further evidence of DGKH as a risk gene for bipolar disorder, but also unipolar depression and adult ADHD.