Image2_A partitioned 88-loci psoriasis genetic risk score reveals HLA and non-HLA contributions to clinical phenotypes in a Newfoundland psoriasis cohort.PDF

• Main Authors: Audrey Bui, Sugandh Kumar, Jared Liu, Faye Orcales, Susanne Gulliver, Lam C. Tsoi, Wayne Gulliver, Wilson Liao
• Format: Still Image
• Language: unknown
• Published: 2023
• Subjects: Genetics; Genetic Engineering; Biomarkers; Developmental Genetics (incl. Sex Determination); Epigenetics (incl. Genome Methylation and Epigenomics); Gene Expression (incl. Microarray and other genome-wide approaches); Genome Structure and Regulation; Genomics; Genetically Modified Animals; Livestock Cloning; Gene and Molecular Therapy; genetic risk score (GRS); polygenic risk score (PRS); psoriasis; Newfoundland and labrador; HLA; Newfoundland
• Online Access: https://doi.org/10.3389/fgene.2023.1141010.s003; https://figshare.com/articles/figure/Image2_A_partitioned_88-loci_psoriasis_genetic_risk_score_reveals_HLA_and_non-HLA_contributions_to_clinical_phenotypes_in_a_Newfoundland_psoriasis_cohort_PDF/23267744

Psoriasis is an immune-mediated inflammatory skin disease typically characterized by erythematous and scaly plaques. It affects 3% of the Newfoundland population while only affecting 1.7% of the general Canadian population. Recent genome-wide association studies (GWAS) in psoriasis have identified more than 63 genetic susceptibility loci that individually have modest effects. Prior studies have shown that a genetic risk score (GRS) combining multiple loci can improve psoriasis disease prediction. However, these prior GRS studies have not fully explored the association of GRS with patient clinical characteristics. In this study, we calculated three types of GRS: one using all known GWAS SNPs (GRS-ALL), one using a subset of SNPs from the HLA region (GRS-HLA), and the last using non-HLA SNPs (GRS-noHLA). We examined the relationship between these GRS and a number of psoriasis features within a well characterized Newfoundland psoriasis cohort. We found that both GRS-ALL and GRS-HLA were significantly associated with early age of psoriasis onset, psoriasis severity, first presentation of psoriasis at the elbow or knee, and the total number of body locations affected, while only GRS-ALL was associated with a positive family history of psoriasis. GRS-noHLA was uniquely associated with genital psoriasis. These findings clarify the relationship of the HLA and non-HLA components of GRS with important clinical features of psoriasis.