1. Association of β-defensin copy number and psoriasis in three cohorts of European origin.
- Author
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Stuart PE, Hüffmeier U, Nair RP, Palla R, Tejasvi T, Schalkwijk J, Elder JT, Reis A, and Armour JAL
- Subjects
- Adult, Aged, Case-Control Studies, Cohort Studies, Data Interpretation, Statistical, Europe, Female, Genetic Association Studies, Germany epidemiology, Humans, Male, Michigan epidemiology, Middle Aged, Netherlands epidemiology, Psoriasis epidemiology, DNA genetics, Gene Dosage genetics, Psoriasis ethnology, Psoriasis genetics, beta-Defensins genetics
- Abstract
A single previous study has demonstrated significant association of psoriasis with copy number of β-defensin genes, using DNA from psoriasis cases and controls from Nijmegen and Erlangen. In this study, we attempted to replicate that finding in larger new cohorts from Erlangen (N=2,017) and Michigan (N=5,412), using improved methods for β-defensin copy number determination based on the paralog ratio test, and enhanced methods of analysis and association testing implemented in the CNVtools resource. We demonstrate that the association with psoriasis found in the discovery sample is maintained after applying improved typing and analysis methods (P=5.5 × 10(-4), odds ratio (OR)=1.25). We also find that the association is replicated in 2,616 cases and 2,526 controls from Michigan, although at reduced significance (P=0.014), but not in new samples from Erlangen (1,396 cases and 621 controls, P=0.38). Meta-analysis across all cohorts suggests a nominally significant association (P=6.6 × 10(-3)/2 × 10(-4)) with an effect size (OR=1.081) much lower than found in the discovery study (OR=1.32). This reduced effect size and significance on replication is consistent with a genuine but weak association.
- Published
- 2012
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