title: Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility.
abstract: Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.
authors.affiliation: 1] Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui 230032, China [2] State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, Anhui 230032, China [3] Key Lab of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui 230032, China [4] Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Xianyong
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.
authors.forename: Hui Qi
authors.initials: HQ
authors.lastname: Low
authors.affiliation: Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Celera, Alameda, California 94502, USA.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelm Street 12, Kiel 24105, Germany.
authors.forename: Eva
authors.identifier: 0000000329143382
authors.initials: E
authors.lastname: Ellinghaus
authors.affiliation: 1] Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana 46202, USA [2] Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana 46202, USA [3] Department of Dermatology, School of Medicine, Indiana University, Indianapolis, Indiana 46202, USA.
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
authors.affiliation: 1] Genetic Causes of Disease Group, Centre for Genomic Regulation (CRG), Barcelona, Catalonia, E-08003, Spain [2] Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Catalonia, E-08003, Spain [3] Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, E-08003, Spain [4] CIBER in Epidemiology and Public Health (CIBERESP), Barcelona, Catalonia, E-08003, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.affiliation: 1] Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui 230032, China [2] State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, Anhui 230032, China [3] Key Lab of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui 230032, China [4] Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Liangdan
authors.initials: L
authors.lastname: Sun
authors.affiliation: 1] Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui 230032, China [2] State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, Anhui 230032, China [3] Key Lab of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui 230032, China [4] Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Xianbo
authors.initials: X
authors.lastname: Zuo
authors.affiliation: 1] Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui 230032, China [2] State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, Anhui 230032, China [3] Key Lab of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui 230032, China [4] Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Changbing
authors.initials: C
authors.lastname: Shen
authors.affiliation: 1] Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui 230032, China [2] State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, Anhui 230032, China [3] Key Lab of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui 230032, China [4] Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Zhu
authors.affiliation: 1] Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui 230032, China [2] State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, Anhui 230032, China [3] Key Lab of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui 230032, China [4] Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Anping
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm 17176, Sweden.
authors.forename: Fabio
authors.initials: F
authors.lastname: Sanchez
authors.affiliation: Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm 17177, Sweden.
authors.forename: Leonid
authors.identifier: 0000000329505670
authors.initials: L
authors.lastname: Padyukov
authors.affiliation: Celera, Alameda, California 94502, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Catanese
authors.affiliation: Department of Dermatology, University of Utah, Salt Lake, Utah 84132, USA.
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Krueger
authors.affiliation: Department of Dermatology, University of Utah, Salt Lake, Utah 84132, USA.
authors.forename: Kristina Callis
authors.initials: KC
authors.lastname: Duffin
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelm Street 12, Kiel 24105, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Mucha
authors.affiliation: Department of Dermatology, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Weichenthal
authors.affiliation: Department of Dermatology, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Weidinger
authors.affiliation: Institute of Epidemiology and Biobank PopGen, Christian Albrechts University, Kiel, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.affiliation: Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.
authors.forename: Jia Nee
authors.identifier: 0000000198992308
authors.initials: JN
authors.lastname: Foo
authors.affiliation: Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.
authors.forename: Karseng
authors.identifier: 0000000238227759
authors.initials: K
authors.lastname: Sim
authors.affiliation: Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.
authors.forename: Herty
authors.initials: H
authors.lastname: Liany
authors.affiliation: Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.
authors.forename: Ishak
authors.initials: I
authors.lastname: Irwan
authors.affiliation: 1] Departments of Statistics and Applied Probability, National University of Singapore, Singapore 138672, Singapore [2] Department of Epidemiology and Public Health, National University of Singapore, Singapore 138672, Singapore.
authors.forename: Yikying
authors.initials: Y
authors.lastname: Teo
authors.affiliation: National Skin Centre, Singapore 308205, Singapore.
authors.forename: Colin T S
authors.initials: CT
authors.lastname: Theng
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, California 94115, USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Gupta
authors.affiliation: National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Bowcock
authors.affiliation: 1] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02138, USA [2] Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham &Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Philip L
authors.initials: PL
authors.lastname: De Jager
authors.affiliation: 1] Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana 46202, USA [2] Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana 46202, USA [3] Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham &Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Abrar A
authors.initials: AA
authors.lastname: Qureshi
authors.affiliation: 1] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands [2] Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands.
authors.forename: Paul I W
authors.identifier: 0000000177357858
authors.initials: PI
authors.lastname: de Bakker
authors.affiliation: 1] Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore [2] Institute for Human Genetics, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Mark
authors.identifier: 0000000157831401
authors.initials: M
authors.lastname: Seielstad
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, California 94115, USA.
authors.forename: Wilson
authors.initials: W
authors.lastname: Liao
authors.affiliation: Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm 17176, Sweden.
authors.forename: Mona
authors.initials: M
authors.lastname: Ståhle
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelm Street 12, Kiel 24105, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.affiliation: 1] Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui 230032, China [2] State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, Anhui 230032, China [3] Key Lab of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui 230032, China [4] Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 1] State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, Anhui 230032, China [2] Key Lab of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui 230032, China [3] Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui 230032, China [4] Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore [5] Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore, 138672, Singapore [6] School of Life Sciences, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics; D005805:Genes, MHC Class I / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D011565:Psoriasis / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C553748:COG6 protein, human; D050676:Core Binding Factor Alpha 2 Subunit; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; C493728:RUNX1 protein, human; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1