The association between 38 previously reported polymorphisms and psoriasis in a Polish population: High predicative accuracy of a genetic risk score combining 16 loci

PLoS One. 2017 Jun 15;12(6):e0179348. doi: 10.1371/journal.pone.0179348. eCollection 2017.

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.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Female
  • Genetic Loci*
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Poland / epidemiology
  • Polymorphism, Single Nucleotide*
  • Psoriasis / epidemiology
  • Psoriasis / genetics*
  • Risk Factors

Grants and funding

This study was supported by the Polish Ministry of Science and Higher Education (grant number N N402 194235).