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

Chen, Guo-Bo, Lee, Sang Hong, Brion, Marie-Jo A., Montgomery, Grant W., Wray, Naomi R., Radford-Smith, Graham L., Visscher, Peter M., The International IBD Genetics Consortium, Australia and New Zealand IBDGC, Belgium Genetic Consortium, Initiative on Crohn and Colitis, NIDDK IBDGC, United Kingdom IBDGC and Wellcome Trust Case Control Consortium (2014) Estimation and partitioning of (co)heritability of inflammatory bowel disease from GWAS and immunochip data. Human Molecular Genetics, 23 17: 4710-4720. doi:10.1093/hmg/ddu174

Author Chen, Guo-Bo
Lee, Sang Hong
Brion, Marie-Jo A.
Montgomery, Grant W.
Wray, Naomi R.
Radford-Smith, Graham L.
Visscher, Peter M.
The International IBD Genetics Consortium
Australia and New Zealand IBDGC
Belgium Genetic Consortium
Initiative on Crohn and Colitis
United Kingdom IBDGC
Wellcome Trust Case Control Consortium
Title Estimation and partitioning of (co)heritability of inflammatory bowel disease from GWAS and immunochip data
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 1460-2083
Publication date 2014-09-01
Year available 2014
Sub-type Article (original research)
DOI 10.1093/hmg/ddu174
Open Access Status DOI
Volume 23
Issue 17
Start page 4710
End page 4720
Total pages 11
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Subject 1312 Molecular Biology
1311 Genetics
2716 Genetics (clinical)
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.
Keyword Genome-Wide Association
Susceptibility Loci
Complex Diseases
Common Snps
Risk Loci
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 613672
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 39 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 39 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 19 Aug 2014, 13:38:09 EST by System User on behalf of Queensland Brain Institute