Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci

Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genomewide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susceptibility loci. Here, we extend our previous meta-analysis of European ancestry by refined genotype call...

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Main Authors:	Tsoi, Lam C, Spain, Sarah L, Ellinghaus, Eva, Stuart, Philip E, Capon, Francesca, Knight, Jo, Tejasvi, Trilokraj, Kang, Hyun M, Allen, Michael H, Lambert, Sylviane, Stoll, Stefan, Weidinger, Stephan, Gudjonsson, Johann E, Koks, Sulev, Kingo, Külli, Esko, Tonu, Das, Sayantan, Metspalu, Andres, Weichenthal, Michael, Enerback, Charlotta, Krueger, Gerald G., Voorhees, John J, Chandran, Vinod, Rosen, Cheryl F, Rahman, Proton, Gladman, Dafna D, Reis, Andre, Nair, Rajan P, Franke, Andre, Barker, Jonathan NWN, Abecasis, Goncalo R, Trembath, Richard C, Elder, James T
Format:	Online
Language:	English
Published:	2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422106/

id	pubmed-4422106
recordtype	oai_dc
spelling	pubmed-44221062015-11-05 Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci Tsoi, Lam C Spain, Sarah L Ellinghaus, Eva Stuart, Philip E Capon, Francesca Knight, Jo Tejasvi, Trilokraj Kang, Hyun M Allen, Michael H Lambert, Sylviane Stoll, Stefan Weidinger, Stephan Gudjonsson, Johann E Koks, Sulev Kingo, Külli Esko, Tonu Das, Sayantan Metspalu, Andres Weichenthal, Michael Enerback, Charlotta Krueger, Gerald G. Voorhees, John J Chandran, Vinod Rosen, Cheryl F Rahman, Proton Gladman, Dafna D Reis, Andre Nair, Rajan P Franke, Andre Barker, Jonathan NWN Abecasis, Goncalo R Trembath, Richard C Elder, James T Article Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genomewide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susceptibility loci. Here, we extend our previous meta-analysis of European ancestry by refined genotype calling and imputation and by the addition of 5,033 cases and 5,707 controls. The combined analysis, consisting of over 15,000 cases and 27,000 controls, identifies five new psoriasis susceptibility loci at genomewide significance (p < 5 × 10−8). The newly identified signals include two that reside in intergenic regions (1q31.1 and 5p13.1) and three residing near PLCL2 (3p24.3), NFKBIZ (3q12.3), and CAMK2G (10q22.2). We further demonstrate that NFKBIZ is a TRAF3IP2–dependent target of IL-17 signaling in human skin keratinocytes, thereby functionally linking two strong candidate genes. These results further integrate the genetics and immunology of psoriasis, suggesting new avenues for functional analysis and improved therapies. 2015-05-05 /pmc/articles/PMC4422106/ /pubmed/25939698 http://dx.doi.org/10.1038/ncomms8001 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Tsoi, Lam C Spain, Sarah L Ellinghaus, Eva Stuart, Philip E Capon, Francesca Knight, Jo Tejasvi, Trilokraj Kang, Hyun M Allen, Michael H Lambert, Sylviane Stoll, Stefan Weidinger, Stephan Gudjonsson, Johann E Koks, Sulev Kingo, Külli Esko, Tonu Das, Sayantan Metspalu, Andres Weichenthal, Michael Enerback, Charlotta Krueger, Gerald G. Voorhees, John J Chandran, Vinod Rosen, Cheryl F Rahman, Proton Gladman, Dafna D Reis, Andre Nair, Rajan P Franke, Andre Barker, Jonathan NWN Abecasis, Goncalo R Trembath, Richard C Elder, James T
spellingShingle	Tsoi, Lam C Spain, Sarah L Ellinghaus, Eva Stuart, Philip E Capon, Francesca Knight, Jo Tejasvi, Trilokraj Kang, Hyun M Allen, Michael H Lambert, Sylviane Stoll, Stefan Weidinger, Stephan Gudjonsson, Johann E Koks, Sulev Kingo, Külli Esko, Tonu Das, Sayantan Metspalu, Andres Weichenthal, Michael Enerback, Charlotta Krueger, Gerald G. Voorhees, John J Chandran, Vinod Rosen, Cheryl F Rahman, Proton Gladman, Dafna D Reis, Andre Nair, Rajan P Franke, Andre Barker, Jonathan NWN Abecasis, Goncalo R Trembath, Richard C Elder, James T Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci
author_facet	Tsoi, Lam C Spain, Sarah L Ellinghaus, Eva Stuart, Philip E Capon, Francesca Knight, Jo Tejasvi, Trilokraj Kang, Hyun M Allen, Michael H Lambert, Sylviane Stoll, Stefan Weidinger, Stephan Gudjonsson, Johann E Koks, Sulev Kingo, Külli Esko, Tonu Das, Sayantan Metspalu, Andres Weichenthal, Michael Enerback, Charlotta Krueger, Gerald G. Voorhees, John J Chandran, Vinod Rosen, Cheryl F Rahman, Proton Gladman, Dafna D Reis, Andre Nair, Rajan P Franke, Andre Barker, Jonathan NWN Abecasis, Goncalo R Trembath, Richard C Elder, James T
author_sort	Tsoi, Lam C
title	Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci
title_short	Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci
title_full	Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci
title_fullStr	Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci
title_full_unstemmed	Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci
title_sort	enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci
description	Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genomewide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susceptibility loci. Here, we extend our previous meta-analysis of European ancestry by refined genotype calling and imputation and by the addition of 5,033 cases and 5,707 controls. The combined analysis, consisting of over 15,000 cases and 27,000 controls, identifies five new psoriasis susceptibility loci at genomewide significance (p < 5 × 10−8). The newly identified signals include two that reside in intergenic regions (1q31.1 and 5p13.1) and three residing near PLCL2 (3p24.3), NFKBIZ (3q12.3), and CAMK2G (10q22.2). We further demonstrate that NFKBIZ is a TRAF3IP2–dependent target of IL-17 signaling in human skin keratinocytes, thereby functionally linking two strong candidate genes. These results further integrate the genetics and immunology of psoriasis, suggesting new avenues for functional analysis and improved therapies.
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422106/
_version_	1613220108702842880

Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci

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