A Weighted Polygenic Risk Score Using 14 Known Susceptibility Variants to Estimate Risk and Age Onset of Psoriasis in Han Chinese

Abstract

With numbers of common variants identified mainly through genome-wide association studies (GWASs), there is great interest in incorporating the findings into screening individuals at high risk of psoriasis. The purpose of this study is to establish genetic prediction models and evaluate its discriminatory ability in psoriasis in Han Chinese population. We built the genetic prediction models through weighted polygenic risk score (PRS) using 14 susceptibility variants in 8,819 samples. We found the risk of psoriasis among individuals in the top quartile of PRS was significantly larger than those in the lowest quartile of PRS (OR = 28.20, P < 2.0×10-16). We also observed statistically significant associations between the PRS, family history and early age onset of psoriasis. We also built a predictive model with all 14 known susceptibility variants and alcohol consumption, which achieved an area under the curve statistic of ~ 0.88. Our study suggests that 14 psoriasis known susceptibility loci have the discriminating potential, as is also associated with family history and age of onset. This is the genetic predictive model in psoriasis with the largest accuracy to date.

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

“…Yin et al described a GRS (further named GRS-Yin) combining 14 SNPs in a Han Chinese population [24]. Apart from the ethnicity, the study by Yin et al differed from our study in terms of age of onset (21.31 years vs. 26.27 years) and proportion of patients with positive family history of Ps (31.34% vs. 43.3%).…”

The impact of age on psoriasis health care in Germany

“…Genomewide association studies have identified human leucocyte antigens that are associated with either type 1 or type 2 psoriasis. However, predicting the exact age of psoriasis onset remains difficult . Moreover, it has not yet been clarified how age predicts psoriasis course, outcomes and response to treatments.…”

A systematic review of diagnostic criteria for psoriasis in adults and children: evidence from studies with a primary aim to develop or validate diagnostic criteria

“…Within the 11 702 studies identified from the search strategy no clinical examination‐based diagnostic criteria for psoriasis in adults or children were found. Only 23 studies met the inclusion criteria; they presented a broad range of diagnostic criteria including genetic, molecular, dermoscopy, confocal microscopy, histopathology, questionnaire‐based, computer‐aided and traditional Chinese medicine criteria (Table S1; see Supporting Information). Sixteen studies were of a case–control design, five studies were case series, one study was cross‐sectional and one study was a Delphi consensus study.…”

“…Seven studies were of a case–control design and one was a cross‐sectional study. Sensitivity and specificity results of the criteria were presented or available on request for five studies; the sensitivity values ranged from 65·6% to 98% and specificity from 58·2% to 100% . Diagnostic accuracy results were often reported as area under the curve, and three studies reported a value ≥0·7 .…”

“…Diagnostic accuracy results were often reported as area under the curve, and three studies reported a value ≥0·7 . Six studies undertook validation testing of their developed criteria; in two studies this was conducted in a separate cohort, but no studies reported validation in their intended population.…”