Study Report - GWAS of Crohn's disease in a British population (HGVST8)
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Explore Study in Browser| Identifier | HGVST8 | |||||||||||||||
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| Study name | GWAS of Crohn's disease in a British population | |||||||||||||||
| Total p-values imported | 107 | |||||||||||||||
| Phenotype(s) tested | Crohn's disease |
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| Study design | Case and control | |||||||||||||||
| Genotype platforms |
Affymetrix 500K Gene Chip | |||||||||||||||
| Abstract | Summary-level data and analysis results of Crohn's Disease (CD) imported from the Wellcome Trust Case Control Consortium project | |||||||||||||||
| Submission information |
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Author communication  |
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| Related links |
WTCCC1 |
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| Background | The Wellcome Trust Case Control Consortium (WTCCC) was formed with a view to exploring the utility, design and analyses of GWA studies. It brought together over 50 research groups from the UK that are active in researching the genetics of common human diseases, with expertise ranging from clinical, through genotyping, to informatics and statistical analysis | |||||||||||||||
| Objectives | The main experiment consisted of a GWA study of 2,000 cases and 3,000 shared controls for a complex human disease of major public health importance, Crohn's Disease (CD). By simultaneously studying Crohn's Disease (CD) with other diseases with differing aetiologies, we hoped to develop in sights, not only into the specific genetic contributions to each of the diseases, but also into differences in allelic architecture across the diseases. A further major aim was to address important methodological issues of relevance to all GWA studies, such as quality control, design and analysis. In addition to our main association results, we address several of these issues below, including the choice of controls for genetic studies, the extent of population structure within Great Britain, sample sizes necessary to detect genetic effects of varying sizes, and improvements in genotype-calling algorithms and analytical methods. | |||||||||||||||
| Key results | In 2001, positional cloning identified CARD15 (caspase recruitment domain family, member 15; NOD2) as the first confirmed CD-susceptibility gene. In the present study, this locus is represented by rs17221417 (P = 9.4x10-12). A second association, on chromosome 5q31 has been widely replicated, although the identity of the causative gene is disputed owing to extensive regional linkage disequilibrium63. Here, the previously described risk haplotype is tagged by rs6596075 (P = 5.4x10-7). The association between CD and SNPs within IL23R (interleukin 23 receptor) is here represented by a cluster of associated SNPs, including rs11805303 (P = 6.5x10-13). The strongest signal for CD in the present scan (at rs10210302; P = 7.1x10-14) maps to the ATG16L1 . The current study identifies four further new strong association signals in CD, rs1000113 (P = 5.1x10-8), rs9858542 (P = 7.7x10-7), rs10883365 (P = 1.4x10-8) ,rs2542151 (P = 4.6x10-8). For full description of results please see publication. | |||||||||||||||
| Conclusions | An emerging theme from molecular genetic studies of CD is the importance of defects in autophagy and the processing of phagocytosed bacteria. A number of other specific components within innate and adaptive immune pathways are also highlighted | |||||||||||||||
| Reason for study size | Not supplied | |||||||||||||||
| Study power | Not supplied | |||||||||||||||
| Sources of bias | Not supplied | |||||||||||||||
| Limitations | Not supplied | |||||||||||||||
| Acknowledgements | The principal funder of this project was the Wellcome Trust. Please see publication for the full list of acknowledgements. | |||||||||||||||
| Related citations |
The Wellcome Trust Case Control Consortium
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007 Jun 7;447(7145):661-78 |
