Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis

Abstract

Genome-wide association studies (GWASs) have reproducibly associated ∼40 susceptibility loci with psoriasis. However, the missing heritability is evident and the contributions of coding variants have not yet been systematically evaluated. Here, we present a large-scale whole-exome array analysis for psoriasis consisting of 42,760 individuals. We discover 16 SNPs within 15 new genes/loci associated with psoriasis, including C1orf141 , ZNF683 , TMC6 , AIM2 , IL1RL1 , CASR , SON , ZFYVE16 , MTHFR , CCDC129 , ZNF143 , AP5B1 , SYNE2 , IFNGR2 and 3q26.2-q27 ( P <5.00 × 10 −08 ). In addition, we also replicate four known susceptibility loci TNIP1 , NFKBIA , IL12B and LCE3D–LCE3E . These susceptibility variants identified in the current study collectively account for 1.9% of the psoriasis heritability. The variant within AIM2 is predicted to impact protein structure. Our findings increase the number of genetic risk factors for psoriasis and highlight new and plausible biological pathways in psoriasis.

Cited by papers we hold 4

• Signaling pathways and targeted therapies for psoriasis · 2023
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• Biology of IL-36 Signaling and Its Role in Systemic Inflammatory Diseases · 2019
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• Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants · 2017
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• Assessing the Power of Exome Chips. · 2015
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