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

Abstract

ObjectivesTo 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 methodsThirty-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.ResultsWe 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.ConclusionsWe 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.

Apremilast Pharmacogenomics in Russian Patients with Moderate-to-Severe and Severe Psoriasis

“…Therein, we found that the consuming significance probability level was 0.05 ( Table 1 ). The polygenic risk score was 38 SNP and was calculated according to Kisiel et al [ 15 ]. AUC values were calculated with the R-package “pROC” software.…”

“…For populations of Caucasian origin, the AUC achieved 0.76 using 63 SNPs [ 13 ]. A recent study created a PV prediction GRS based on 38 highly associated SNP [ 15 ]. In this study, we used GRS to differentiate patients with severe and moderate-to severe PV from the general Russian population.…”

Long Noncoding RNA HCP5, a Hybrid HLA Class I Endogenous Retroviral Gene: Structure, Expression, and Disease Associations

“…The authors also noted that the same significant HCP5 SNV in psoriasis and HIV infections is not surprising since psoriasis can be triggered by infection with HIV and other viruses. Hence, it is possible that HCP5 - C carriers mount a strong immune reaction to viral infection, and when psoriasis is associated with other genes such as corneodesmosin, POU5F1, MICA , and HLA-C in the MHC and genes outside the MHC in genetically susceptible individuals [116], then this reaction might lead to excessive inflammation in skin and joints.…”

Candidate long‐range regulatory sites acting on the IL17 pathway genes TRAF3IP2 and IL17RA are associated with psoriasis

“…Accordingly, genetic associations between psoriasis and IL‐17 pathway genes, including IL23R and the key signal transducer TRAF3IP2 (also called ACT1 ), have been reported. Nevertheless, the overall risk conferred by these variants remains moderate (mean OR: 1.98 for IL23R and 1.11 for TRAF3IP2 , respectively), and, despite acting as direct drug targets, no genetic association has been identified for IL17F , IL17A or IL17RA . It remains unclear whether the frequency of disruptive mutations in these genes is too low to have been detectable by existing studies.…”