Study Report - GWAS of rheumatoid arthritis in a British population (HGVST10)
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Explore Study in Browser| Identifier | HGVST10 | |||||||||||||||
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| Study name | GWAS of rheumatoid arthritis in a British population | |||||||||||||||
| Total p-values imported | 61 | |||||||||||||||
| Phenotype(s) tested | Rheumatoid arthritis |
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| Study design | Case and control | |||||||||||||||
| Genotype platforms |
Affymetrix 500K Gene Chip | |||||||||||||||
| Abstract | Summary-level data and analysis results of Rheumatoid Arthritis (RA) 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, Rheumatoid Arthritis (RA). 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 | RA was the sole disease for which the sex-differentiated analysis generated a strong signal due to different genetic effects in males and females. The SNP rs11761231 (chromosome 7) generates a P value of 3.9x10-7 for the 2-degrees of freedom (d.f.) sex-differentiated test which combines trend tests in males and females. (The trend test ignoring the sex of the individuals has a P value of 1.7x10-6.) This genotype has no effect on disease status in males, but a strong apparently additive effect in females (P value in a logistic regression model with additive log-odds is 0.68 in males and 6.8 10-8 in females, additive OR for females 1.32), and may represent one of the first sex-differentiated effects in human diseases. None of the 9 SNPs with nominal P values in the range 10-5 to 5x10-7 map to loci previously associated with RA. For full description of the results please see publication. | |||||||||||||||
| Conclusions | These findings for RA may represent one of the first sex-differentiated effects in human diseases. | |||||||||||||||
| 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 |
