BACKGROUND: Psoriasis has long been considered as a complex disease, and gene-gene or gene-environment interactions may jointly influence the etiology for psoriasis. OBJECTIVE: We evaluated the associations of single nucleotide polymorphisms (SNPs) in MHC region, and determined the epistasis and combined effects of MHC locus and IL12B, LCE on risk for psoriasis. METHODS: We genotyped SNP rs1265181 (MHC) in 5067 cases and 6404 controls, combining with the prior GWAS data (1139 cases and 1132 controls), we explored the genetic interaction among MHC locus, LCE and IL12B by using logistic regression analysis. We evaluated the combined effects of MHC locus and two non-MHC loci in the combined sample of 6206 cases and 7536 controls. RESULTS: Extremely high significance of association was detected between rs1265181 and psoriasis (p combined < 10E--300, OR = 16.52, 95% CI: 15.28-18.44). We observed significant interactions between MHC and LCE (p = 0.0016) and between MHC and IL12B (p = 0.0036). The risk increased some 26-fold in individuals with risk alleles in both MHC and LCE as compared with those without risk alleles, and individual carrying risk alleles of MHC and IL12B has around 36-fold higher risk of psoriasis than those with protective alleles. CONCLUSIONS: This study provides evidence for the epistatic effects between MHC locus and LCE, IL12B genes. Besides, we suggest that MHC might be the main effect gene on the risk for psoriasis. This data may contribute to our understanding of psoriasis genetic interactions and account for the additional risk of certain patients to develop psoriasis. Crown
BACKGROUND:Psoriasis has long been considered as a complex disease, and gene-gene or gene-environment interactions may jointly influence the etiology for psoriasis. OBJECTIVE: We evaluated the associations of single nucleotide polymorphisms (SNPs) in MHC region, and determined the epistasis and combined effects of MHC locus and IL12B, LCE on risk for psoriasis. METHODS: We genotyped SNP rs1265181 (MHC) in 5067 cases and 6404 controls, combining with the prior GWAS data (1139 cases and 1132 controls), we explored the genetic interaction among MHC locus, LCE and IL12B by using logistic regression analysis. We evaluated the combined effects of MHC locus and two non-MHC loci in the combined sample of 6206 cases and 7536 controls. RESULTS: Extremely high significance of association was detected between rs1265181 and psoriasis (p combined < 10E--300, OR = 16.52, 95% CI: 15.28-18.44). We observed significant interactions between MHC and LCE (p = 0.0016) and between MHC and IL12B (p = 0.0036). The risk increased some 26-fold in individuals with risk alleles in both MHC and LCE as compared with those without risk alleles, and individual carrying risk alleles of MHC and IL12B has around 36-fold higher risk of psoriasis than those with protective alleles. CONCLUSIONS: This study provides evidence for the epistatic effects between MHC locus and LCE, IL12B genes. Besides, we suggest that MHC might be the main effect gene on the risk for psoriasis. This data may contribute to our understanding of psoriasis genetic interactions and account for the additional risk of certain patients to develop psoriasis. Crown
Authors: Philip E Stuart; Rajan P Nair; Lam C Tsoi; Trilokraj Tejasvi; Sayantan Das; Hyun Min Kang; Eva Ellinghaus; Vinod Chandran; Kristina Callis-Duffin; Robert Ike; Yanming Li; Xiaoquan Wen; Charlotta Enerbäck; Johann E Gudjonsson; Sulev Kõks; Külli Kingo; Tõnu Esko; Ulrich Mrowietz; Andre Reis; H Erich Wichmann; Christian Gieger; Per Hoffmann; Markus M Nöthen; Juliane Winkelmann; Manfred Kunz; Elvia G Moreta; Philip J Mease; Christopher T Ritchlin; Anne M Bowcock; Gerald G Krueger; Henry W Lim; Stephan Weidinger; Michael Weichenthal; John J Voorhees; Proton Rahman; Peter K Gregersen; Andre Franke; Dafna D Gladman; Gonçalo R Abecasis; James T Elder Journal: Am J Hum Genet Date: 2015-11-28 Impact factor: 11.025
Authors: Lam C Tsoi; Sarah L Spain; Jo Knight; Eva Ellinghaus; Philip E Stuart; Francesca Capon; Jun Ding; Yanming Li; Trilokraj Tejasvi; Johann E Gudjonsson; Hyun M Kang; Michael H Allen; Ross McManus; Giuseppe Novelli; Lena Samuelsson; Joost Schalkwijk; Mona Ståhle; A David Burden; Catherine H Smith; Michael J Cork; Xavier Estivill; Anne M Bowcock; Gerald G Krueger; Wolfgang Weger; Jane Worthington; Rachid Tazi-Ahnini; Frank O Nestle; Adrian Hayday; Per Hoffmann; Juliane Winkelmann; Cisca Wijmenga; Cordelia Langford; Sarah Edkins; Robert Andrews; Hannah Blackburn; Amy Strange; Gavin Band; Richard D Pearson; Damjan Vukcevic; Chris C A Spencer; Panos Deloukas; Ulrich Mrowietz; Stefan Schreiber; Stephan Weidinger; Sulev Koks; Külli Kingo; Tonu Esko; Andres Metspalu; Henry W Lim; John J Voorhees; Michael Weichenthal; H Erich Wichmann; Vinod Chandran; Cheryl F Rosen; Proton Rahman; Dafna D Gladman; Christopher E M Griffiths; Andre Reis; Juha Kere; Rajan P Nair; Andre Franke; Jonathan N W N Barker; Goncalo R Abecasis; James T Elder; Richard C Trembath Journal: Nat Genet Date: 2012-11-11 Impact factor: 38.330
Authors: Mari H Tervaniemi; H Annika Siitonen; Cilla Söderhäll; Gurinder Minhas; Jyrki Vuola; Inkeri Tiala; Raija Sormunen; Lena Samuelsson; Sari Suomela; Juha Kere; Outi Elomaa Journal: PLoS One Date: 2012-11-26 Impact factor: 3.240