title: Estimation and partitioning of (co)heritability of inflammatory bowel disease from GWAS and immunochip data.
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 data was lost using the iChip due to the 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.
authors.affiliation: The Queensland Brain Institute and.
authors.forename: Guo-Bo
authors.initials: GB
authors.lastname: Chen
authors.affiliation: The Queensland Brain Institute and.
authors.forename: Sang Hong
authors.initials: SH
authors.lastname: Lee
authors.affiliation: The Queensland Brain Institute and.
authors.forename: Marie-Jo A
authors.initials: MJ
authors.lastname: Brion
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.affiliation: The Queensland Brain Institute and.
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Wray
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, QLD, Australia Inflammatory Bowel Disease Research Group, Immunology Division, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia Department of Gastroenterology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
authors.forename: Graham L
authors.initials: GL
authors.lastname: Radford-Smith
authors.affiliation: The Queensland Brain Institute and The University of Queensland Diamantina Institute, Brisbane, QLD, Australia peter.visscher@uq.edu.au.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Visscher
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D040582:Inheritance Patterns / Q000235:genetics*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018401:Sample Size
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