Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis

Nat Commun. 2015 Apr 9;6:6793. doi: 10.1038/ncomms7793.

Abstract

Genome-wide association studies (GWASs) have reproducibly associated ∼40 susceptibility loci with psoriasis. However, the missing heritability is evident and the contributions of coding variants have not yet been systematically evaluated. Here, we present a large-scale whole-exome array analysis for psoriasis consisting of 42,760 individuals. We discover 16 SNPs within 15 new genes/loci associated with psoriasis, including C1orf141, ZNF683, TMC6, AIM2, IL1RL1, CASR, SON, ZFYVE16, MTHFR, CCDC129, ZNF143, AP5B1, SYNE2, IFNGR2 and 3q26.2-q27 (P<5.00 × 10(-08)). In addition, we also replicate four known susceptibility loci TNIP1, NFKBIA, IL12B and LCE3D-LCE3E. These susceptibility variants identified in the current study collectively account for 1.9% of the psoriasis heritability. The variant within AIM2 is predicted to impact protein structure. Our findings increase the number of genetic risk factors for psoriasis and highlight new and plausible biological pathways in psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics
  • Adolescent
  • Adult
  • Asians / genetics*
  • Case-Control Studies
  • Cornified Envelope Proline-Rich Proteins / genetics
  • DNA-Binding Proteins / genetics
  • Exome / genetics
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • I-kappa B Proteins / genetics
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-12 Subunit p40 / genetics
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Membrane Proteins / genetics
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Microfilament Proteins / genetics
  • Middle Aged
  • Minor Histocompatibility Antigens
  • NF-KappaB Inhibitor alpha
  • Nerve Tissue Proteins / genetics
  • Nuclear Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Psoriasis / genetics*
  • Receptors, Calcium-Sensing / genetics
  • Receptors, Cell Surface / genetics
  • Receptors, Interferon / genetics
  • Serine Endopeptidases / genetics
  • Trans-Activators / genetics
  • Young Adult

Substances

  • AIM2 protein, human
  • AP5B1 protein, human
  • Adaptor Proteins, Vesicular Transport
  • CASR protein, human
  • Cornified Envelope Proline-Rich Proteins
  • DNA-Binding Proteins
  • I-kappa B Proteins
  • IFNGR2 protein, human
  • IL12B protein, human
  • IL1RL1 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-12 Subunit p40
  • Intracellular Signaling Peptides and Proteins
  • LCE3D protein, human
  • Membrane Proteins
  • Microfilament Proteins
  • Minor Histocompatibility Antigens
  • NFKBIA protein, human
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface
  • Receptors, Interferon
  • SON protein, human
  • SYNE2 protein, human
  • TMC6 protein, human
  • TNIP1 protein, human
  • Trans-Activators
  • ZNF143 protein, human
  • NF-KappaB Inhibitor alpha
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • ZFYVE16 protein, human
  • Serine Endopeptidases