1. The association between 38 previously reported polymorphisms and psoriasis in a Polish population: High predicative accuracy of a genetic risk score combining 16 loci.
- Author
-
Kisiel B, Kisiel K, Szymański K, Mackiewicz W, Biało-Wójcicka E, Uczniak S, Fogtman A, Iwanicka-Nowicka R, Koblowska M, Kossowska H, Placha G, Sykulski M, Bachta A, Tłustochowicz W, Płoski R, and Kaszuba A
- Subjects
- Adolescent, Adult, Child, Female, Humans, Male, Poland epidemiology, Psoriasis epidemiology, Risk Factors, Genetic Loci, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Psoriasis genetics
- Abstract
Objectives: To confirm the association of previously discovered psoriasis (Ps) risk loci with the disease in a Polish population and to create predictive models based on the combination of these single nucleotide polymorphisms (SNPs)., Material and Methods: Thirty-eight SNPs were genotyped in 480 Ps patients and 490 controls. Alleles distributions were compared between patients and controls, as well as between different Ps sub-phenotypes. The genetic risk score (GRS) was calculated to assess the cumulative risk conferred by multiple loci., Results: We confirmed associations of several loci with Ps: HLA-C, REL, IL12B, TRIM39/RPP21, POU5F1, MICA. The analysis of ROC curves showed that GRS combining 16 SNPs at least nominally (uncorrected P<0.05) associated with Ps (GRS-N) had significantly better discriminative power than GRS combining SNPs associated with Ps after the Bonferroni correction (AUC 0.776 vs. 0.750, P = 1 x 10-4) or HLA-C (AUC 0.776 vs. 0.694, P<1 x 10-5). On the other hand, adding additional SNPs to the model did not improve its discriminatory ability (AUC 0.782 for GRS combining all SNPs, P>0.05). In order to assess the total risk conferred by GRS-N, we calculated ORs according to GRS-N quartile - the Ps OR for top vs. bottom GRS-N quartiles was 12.29 (P<1 x 10-6). The analysis of different Ps sub-phenotypes showed an association of GRS-N with age of onset and family history of Ps., Conclusions: We confirmed the association of Ps with several previously identified genetic risk factors in a Polish population. We found that a GRS combining 16 SNPs at least nominally associated with Ps had a significantly better discriminatory ability than HLA-C or GRS combining SNPs associated with Ps after the Bonferroni correction. In contrast, adding additional SNPs to GRS did not increase significantly the discriminative power.
- Published
- 2017
- Full Text
- View/download PDF