Integration of expression quantitative trait loci and pleiotropy identifies a novel psoriasis susceptibility gene, PTPN1

J Gene Med. 2017 Jan;19(1-2). doi: 10.1002/jgm.2939.

Abstract

Background: Psoriasis is a common inflammatory skin disease, whereas schizophrenia is a psychiatric disorder with substantial comorbidity. Although these two disorders manifest with apparently unrelated phenotypes, there is some evidence suggesting that they share common genetic factors.

Methods: We implemented a genetic analysis incorporating pleiotropy and annotation to genome-wide association summary statistics data for approximately 120 000 psoriasis and schizophrenia samples, as well as whole blood expression quantitative trait loci in 5311 samples.

Results: We observed a significant pleiotropic effect between psoriasis and schizophrenia (p = 5.92 × 10-43 ). We characterized an enrichment of whole blood expression quantitative trait loci in genome-wide association data for psoriasis and schizophrenia (q1 /q0 > 1.5, p < 10-77 ) and we revealed that common variants for both diseases were more likely to confer expression quantitative trait loci effects (q1 /q0 = 4.197, SE = 0.183). Through joint analysis of the associations in the combined psoriasis and schizophrenia data set, we identified a potential susceptibility PTPN1 gene for psoriasis, which may affect the risk of psoriasis through modulation of the function of TYK2 kinase.

Conclusions: The results of the present study highlight the expression quantitative trait loci enrichment and pleiotropy in psoriasis and schizophrenia, and also suggest a possible key role of the PTPN1 gene in the etiology of psoriasis.

Keywords: genome wide association study; pleiotropy; psoriasis; schizophrenia.

MeSH terms

  • Alleles
  • Computational Biology / methods
  • Gene Expression*
  • Genetic Association Studies*
  • Genetic Pleiotropy / genetics*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genomics
  • Genotype
  • HLA Antigens / genetics
  • Humans
  • Polymorphism, Single Nucleotide
  • Protein Interaction Mapping
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / genetics*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Psoriasis / diagnosis
  • Psoriasis / genetics*
  • Psoriasis / metabolism
  • Quantitative Trait Loci*
  • Schizophrenia / genetics
  • Signal Transduction

Substances

  • HLA Antigens
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1