Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility

Yin, Xianyong; Low, Hui Qi; Wang, Ling; Li, Yonghong; Ellinghaus, Eva; Han, Jiali; Estivill, Xavier; Sun, Liangdan; Zuo, Xianbo; Shen, Changbing; Zhu, Caihong; Zhang, Anping; Sánchez, Fabio; Padyukov, Leonid; Catanese, Joseph J.; Krueger, Gerald G.; Duffin, Kristina Callis; Mucha, Sören; Weichenthal, Michael; Weidinger, Stephan; Lieb, Wolfgang; Foo, Jia Nee; Li, Yang; Sim, Kar Seng; Liany, Herty; Irwan, Ishak D.; Teo, Yik-Ying; Theng, Colin; Gupta, Rashmi; Bowcock, Anne M.; Jager, Philip L. De; Qureshi, Abrar A.; Bakker, Paul I. W. de; Seielstad, Mark; Liao, Wilson; Ståhle, Mona; Franke, André; Zhang, Xuejun; Liu, Jing

doi:10.1038/ncomms7916

Cited by 171 publications

(136 citation statements)

References 56 publications

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“…This study did not address T1D association with the rs1990760 SNP nor the other two noted above and therefore cannot rule out their effects. In contrast to this study, in a GWA meta-analysis of psoriasis-associated SNPs, Weidinger et al noted that conditioning the analysis on rs1990760 polymorphism negated the association of rs2111485 with psoriasis [48].…”

Section: T1d-associated Common Ifih1 Snpsmentioning

confidence: 83%

Effects of Type 1 Diabetes-Associated IFIH1 Polymorphisms on MDA5 Function and Expression

et al. 2015

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Recent evidence has highlighted the role of the innate immune system in type 1 diabetes (T1D) pathogenesis. Specifically, aberrant activation of the interferon response prior to seroconversion of T1D-associated autoantibodies supports a role for the interferon response as a precipitating event toward activation of autoimmunity. Melanoma differentiation-associated protein 5 (MDA5), encoded by IFIH1, mediates the innate immune system's interferon response to certain viral species that form double-stranded RNA (dsRNA), the MDA5 ligand, during their life cycle. Extensive research has associated single nucleotide polymorphisms (SNPs) within the coding region of IFIH1 with T1D. This review discusses the different risk and protective IFIH1 alleles in the context of recent structural and functional analysis that relate to MDA5 regulation of interferon responses. These studies have provided a functional hypothesis for IFIH1 T1D-associated SNPs' effects on MDA5-mediated interferon responses as well as supporting the genome-wide association (GWA) studies that first associated IFIH1 with T1D.

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Section: T1d-associated Common Ifih1 Snpsmentioning

confidence: 83%

Effects of Type 1 Diabetes-Associated IFIH1 Polymorphisms on MDA5 Function and Expression

et al. 2015

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“…Psoriasis is a chronic inflammatory skin disease that affects approximately 3% of the US population, 2.5% of the European population and 0.1~0.5% of Asians (Yin et al, 2015). Progress in understanding the etiology of this disease has revealed it to be a complicated immune system disorder involving the dynamic interplay of innate and adaptive immunity, with participation of several cell types including epidermal keratinocytes (KC), T lymphocytes, dendritic cells (DCs) and neutrophils (Lowes et al, 2007; Sweeney et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-β Production by Epidermal Keratinocytes during Skin Injury

et al. 2016

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SUMMARY Type 1 interferons (IFN) promote inflammation in the skin but the mechanisms responsible for inducing these cytokines are not well understood. We found that IFNβ was abundantly produced by epidermal keratinocytes (KCs) in psoriasis and during wound repair. KC IFNβ production depended on stimulation of mitochondrial antiviral-signaling protein (MAVS) by the antimicrobial peptide LL37 and double stranded-RNA released from necrotic cells. MAVS activated downstream TBK1 (TANK-Binding Kinase 1)-AKT (AKT serine/threonine kinase 1)-IRF3 (interferon regulatory factor 3) signaling cascade leading to IFNβ production, and then promoted maturation of dendritic cells. In mice, the production of epidermal IFNβ by LL37 required MAVS, and human wounded and/or psoriatic skin showed activation of MAVS-associated IRF3 and induction of MAVS and IFNβ gene signatures. These findings show that KCs are an important source of IFNβ and MAVS is critical to this function, and demonstrates how the epidermis triggers unwanted skin inflammation under disease conditions.

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“…Findings were validated from the summary statistics of 2 GWAS in schizophrenia 35 (1630 cases and 1860 controls) and psoriasis 36 (441 cases and 2420 controls) of Singapore Chinese descent. The schizophrenia data set came from the Singapore Translational and Clinical Research in Psychosis (STCRP) Study.…”

Section: Independent Validationmentioning

confidence: 96%

Common susceptibility variants are shared between schizophrenia and psoriasis in the Han Chinese population

Yin

Wang²,

Yue³

et al. 2016

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Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility

Cited by 171 publications

References 56 publications

Effects of Type 1 Diabetes-Associated IFIH1 Polymorphisms on MDA5 Function and Expression

Effects of Type 1 Diabetes-Associated IFIH1 Polymorphisms on MDA5 Function and Expression

Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-β Production by Epidermal Keratinocytes during Skin Injury

Common susceptibility variants are shared between schizophrenia and psoriasis in the Han Chinese population

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