Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility

Nat Commun. 2015 Apr 23;6:6916. doi: 10.1038/ncomms7916.

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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics
  • Asian Continental Ancestry Group / genetics*
  • Case-Control Studies
  • Core Binding Factor Alpha 2 Subunit / genetics
  • DEAD-box RNA Helicases / genetics
  • European Continental Ancestry Group / genetics*
  • Genes, MHC Class I / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Interferon-Induced Helicase, IFIH1
  • Interleukin-12 Subunit p40 / genetics
  • Psoriasis / genetics*
  • Transcription Factors / genetics
  • Tumor Suppressor Proteins / genetics

Substances

  • Adaptor Proteins, Vesicular Transport
  • COG6 protein, human
  • Core Binding Factor Alpha 2 Subunit
  • IL12B protein, human
  • Interleukin-12 Subunit p40
  • RUNX1 protein, human
  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1