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

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 m...

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Bibliographic Details
Published in:Frontiers in Genetics
Main Authors: Audrey Bui, Sugandh Kumar, Jared Liu, Faye Orcales, Susanne Gulliver, Lam C. Tsoi, Wayne Gulliver, Wilson Liao
Format: Article in Journal/Newspaper
Language:English
Published: Frontiers Media S.A. 2023
Subjects:
genetic risk score (GRS)
polygenic risk score (PRS)
psoriasis
Newfoundland and labrador
genetics
HLA
QH426-470
Newfoundland
Online Access:https://doi.org/10.3389/fgene.2023.1141010
https://doaj.org/article/dff61e8cffd64a5a80656b21b64879e7
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Summary: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.

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