title: A large-scale screen for coding variants predisposing to psoriasis.
abstract: To explore the contribution of functional coding variants to psoriasis, we analyzed nonsynonymous single-nucleotide variants (SNVs) across the genome by exome sequencing in 781 psoriasis cases and 676 controls and through follow-up validation in 1,326 candidate genes by targeted sequencing in 9,946 psoriasis cases and 9,906 controls from the Chinese population. We discovered two independent missense SNVs in IL23R and GJB2 of low frequency and five common missense SNVs in LCE3D, ERAP1, CARD14 and ZNF816A associated with psoriasis at genome-wide significance. Rare missense SNVs in FUT2 and TARBP1 were also observed with suggestive evidence of association. Single-variant and gene-based association analyses of nonsynonymous SNVs did not identify newly associated genes for psoriasis in the regions subjected to targeted resequencing. This suggests that coding variants in the 1,326 targeted genes contribute only a limited fraction of the overall genetic risk for psoriasis.
authors.affiliation: 1] Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, China. [2].
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authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China. [3].
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authors.affiliation: 1] Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, China. [2].
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authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2].
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authors.affiliation: 1] Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, China. [2].
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authors.affiliation: BGI-Shenzhen, Shenzhen, China.
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authors.affiliation: Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, China.
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authors.affiliation: Department of Dermatology, Jining No. 1 People's Hospital, Jining, Shandong, China.
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authors.affiliation: Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, China.
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authors.affiliation: BGI-Shenzhen, Shenzhen, China.
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authors.affiliation: Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, China.
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authors.affiliation: BGI-Shenzhen, Shenzhen, China.
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authors.affiliation: Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, China.
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authors.affiliation: Department of Dermatology, Second Hospital, Chengdu, China.
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authors.affiliation: Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, China.
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authors.affiliation: Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, China.
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authors.affiliation: Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, China.
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authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. [3] Department of Biology, University of Copenhagen, Copenhagen, Denmark.
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mesh_terms: D000328:Adult; D000626:Aminopeptidases / Q000235:genetics; D044466:Asian People / Q000235:genetics; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics; D016022:Case-Control Studies; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006162:Guanylate Cyclase / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D055815:Young Adult; D000097631:Galactoside 2-alpha-L-fucosyltransferase; D000099253:Trans-Activation Responsive RNA-Binding Protein
chemical_list: D000626:Aminopeptidases; D053468:CARD Signaling Adaptor Proteins; D000072259:Connexin 26; D017630:Connexins; D005647:Fucosyltransferases; D006162:Guanylate Cyclase; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D018123:Receptors, Interleukin; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C000607042:GJB2 protein, human; C515500:IL23R protein, human; C071598:TARBP1 protein, human; D000099253:Trans-Activation Responsive RNA-Binding Protein; C464841:ERAP1 protein, human; C426243:CARD14 protein, human