报告题目：Estimation and partitioning of (co)heritability of inflammatory bowel disease from GWAS and immunochip data
主要内容：As custom arrays are cheaper than generic GWAS arrays, larger sample size is achievable for gene discovery. Custom arrays can tag more variants through denser genotyping of SNPs at associated loci, but at the cost of losing genome-wide coverage, and the balance between these opposing forces is important for experimental design. We quantified both the gain in captured heritability at known candidate regions and the loss due to imperfect genome-wide coverage for inflammatory bowel disease using immunochip (iChip) and imputed GWAS data on 61,251 and 38,550 samples, respectively. For Crohn’s disease (CD), the iChip and GWAS data explained 19% and 26% of variation in liability, and SNPs in the densely genotyped iChip regions explained 13% and 13% of the heritability in the iChip and GWAS data, respectively. For ulcerative colitis (UC), the iChip and GWAS data explained 15% and 19% of variation in liability, respectively, and the dense iChip regions explained 10% and 9% of the heritability in the iChip and the GWAS data. From bivariate analyses, estimates of the genetic correlation in risk between CD and UC were 0.75 (SE 0.017) and 0.62 (SE 0.042) for the iChip and GWAS data, respectively. For both diseases, the densely genotyped regions on the iChip tagged at least as much variation in liability as in the corresponding regions on the GWAS data, yet about one quarter of tagged heritability on GWAS data was lost using the iChip with low coverage at unselected regions. These results imply that custom arrays with a GWAS backbone will facilitate more gene discovery, both at associated and novel loci.