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Zuo X.,Anhui Medical University | Zuo X.,Fudan University | Zuo X.,State Key Laboratory Incubation of Dermatology | Zuo X.,Key Laboratory of Dermatology | And 127 more authors.
Nature Communications | Year: 2015

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. © 2015 Macmillan Publishers Limited. All rights reserved.

Wang W.-J.,Anhui Medical University | Wang W.-J.,Key Laboratory of Dermatology | Wang W.-J.,State Key Laboratory Incubation of Dermatology | Yin X.-Y.,Anhui Medical University | And 20 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2013

Background Psoriasis is a common chronic inflammatory skin disease. IL23/Th17 is a newly confirmed pathway in psoriasis. Objective To investigate the gene-gene interactions in IL23/Th17 pathway underlying psoriasis. Methods A total of 299 single-nucleotide polymorphisms from 11 genes in IL23/Th17 pathway were genotyped on 1139 patients with psoriasis and 1694 controls. Multifactor dimensionality reduction and logistic regression algorithms were applied to explore the gene-gene interactions. Results We found that there were a three-way interaction among IL21, CCR4 and TNF(χ2 = 5.02(1), P = 0.025) and three pair-wise gene-gene interactions between IL12RB1 and CCR4(χ2 = 11.66(4), P = 0.0201), IL22 and CCR4 (χ2 = 11.97(4), P = 0.0176), IL12RB1 and IL6 (χ2 = 7.31(1), P = 0.0069) in psoriasis. Conclusions Our results might be helpful for explaining the missing heritability of the psoriasis due to epistasis and provide a deep insight into the important role of the IL23/Th17 pathway in the pathogenesis of psoriasis. © 2012 European Academy of Dermatology and Venereology.

Cheng H.,Anhui Medical University | Cheng H.,State Key Laboratory Incubation of Dermatology | Li Y.,Anhui Medical University | Li Y.,State Key Laboratory Incubation of Dermatology | And 51 more authors.
Journal of Investigative Dermatology | Year: 2014

Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To further advance gene discovery, we extended our genome-wide association study data set of 1,139 cases and 2,234 controls and replicated two independent cohorts of 7,200 cases and 10,491 controls. We identified the missense variant rs2303138 (p.Ala763Thr) within the LNPEP gene associated with psoriasis (P combined =1.83 × 10 -13, odds ratio=1.16) and validated four previously reported genes: IL28RA, NFKBIA, TRAF3IP2, and CARD14 (9.74 × 10 -11 ≤P≤9.37 × 10 -5), which confirmed the involvement of the nuclear factor-κB signaling pathway in psoriasis pathogenesis. LNPEP, also named insulin-responsive aminopeptidase, was identified as an angiotensin IV receptor. Protein function prediction suggested that this missense variant of LNPEP was most likely deleterious. Expression analysis showed that LNPEP was significantly downregulated in psoriatic lesions compared with the control skin (P=1.44 × 10 -6) and uninvolved patient skin (P=2.95 × 10 -4). Pathway analysis indicated that LNPEP was involved in the renin-angiotensin system, which also has a key role in cardiovascular disease and diabetes. These results provided genetic evidence that psoriasis might share common mechanisms with hypertension and diabetes, which was consistent with clinical observations. Our study identified a genetic susceptibility factor and provided genetic evidence of insight into psoriasis pathogenesis with the involvement of the renin-angiotensin system pathway. © 2014 The Society for Investigative Dermatology.

PubMed | Anhui Medical University and State Key Laboratory Incubation of Dermatology
Type: Journal Article | Journal: The Journal of dermatology | Year: 2016

Dermatomyositis (DM) is a polygenic disorder characterized by inflammation of skeletal muscle and skin. To date, the exact etiopathogenesis of DM remains elusive. To explore the genetic basis of DM, we conducted genome-wide genotyping analysis of 127 patients and 1566 healthy controls by Illumina Human OmniZhongHua-8 BeadChips in the Chinese Han population. We investigated whether the three SNP (rs7750458, rs9501251 and rs9500928) at 6p21.32 in the HLA-DPB1 gene were significantly associated with DM (P < 5 10

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