Estimation and partitioning of (co)heritability of inflammatory bowel disease from GWAS and immunochip data

Guo Bo Chen, Sang Hong Lee, Marie Jo A. Brion, Grant W. Montgomery, Naomi R. Wray, Graham L. Radford-Smith, Peter M. Visscher

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55 Citations (Scopus)

Abstract

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. Balancing this trade-off is important for maximizing experimental designs. We quantified both the gain in captured SNP-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, respectively, and SNPs in the densely genotyped iChip regions explained 13% of the SNP-heritability for both the iChip and GWAS data. 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 SNP-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. We also quantified the SNP-heritability of genomic regions that did or did not contain the previous 163 GWAS hits for CD and UC, and SNP-heritability of the overlapping loci between the densely genotyped iChip regions and the 163 GWAS hits. For both diseases, over different genomic partitioning, the densely genotyped regions on the iChip tagged at least as much variation in liability as in the corresponding regions in the GWAS data, however a certain amount of tagged SNP-heritability in the GWAS datawas lost using the iChip due to the low coverage at unselected regions. These results imply that custom arrays with a GWAS back bone will facilitatemore gene discovery, bothat associated and novel loci.

Original languageEnglish
Article numberddu174
Pages (from-to)4710-4720
Number of pages11
JournalHuman Molecular Genetics
Volume23
Issue number17
DOIs
Publication statusPublished - Sep 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Chen, G. B., Lee, S. H., Brion, M. J. A., Montgomery, G. W., Wray, N. R., Radford-Smith, G. L., & Visscher, P. M. (2014). Estimation and partitioning of (co)heritability of inflammatory bowel disease from GWAS and immunochip data. Human Molecular Genetics, 23(17), 4710-4720. [ddu174]. https://doi.org/10.1093/hmg/ddu174