title: Association of β-defensin copy number and psoriasis in three cohorts of European origin.
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.
authors: Department of Dermatology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan, USA.
authors: Philip E
authors: PE
authors: Stuart
authors: Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
authors: Ulrike
authors: U
authors: Hüffmeier
authors: Department of Dermatology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan, USA.
authors: Rajan P
authors: RP
authors: Nair
authors: School of Biology, University of Nottingham, Queen's Medical Centre, Nottingham, UK.
authors: Raquel
authors: R
authors: Palla
authors: Department of Dermatology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan, USA.
authors: Trilokraj
authors: T
authors: Tejasvi
authors: Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors: Joost
authors: J
authors: Schalkwijk
authors: Department of Dermatology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan, USA.
authors: James T
authors: JT
authors: Elder
authors: Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
authors: Andre
authors: A
authors: Reis
authors: School of Biology, University of Nottingham, Queen's Medical Centre, Nottingham, UK. Electronic address: John.Armour@nottingham.ac.uk.
authors: John A L
authors: JAL
authors: Armour
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D004247:DNA / Q000235:genetics*; D003627:Data Interpretation, Statistical; D005060:Europe; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D056726:Genetic Association Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008824:Michigan / Q000453:epidemiology; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011565:Psoriasis / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D023083:beta-Defensins / Q000235:genetics*
chemical_list: D023083:beta-Defensins; D004247:DNA