Genotype combination contributes to psoriasis: An exhaustive algorithm perspective

PLoS One. 2017 Oct 11;12(10):e0186067. doi: 10.1371/journal.pone.0186067. eCollection 2017.

Abstract

Researchers have learned that nearly all conditions and diseases have a genetic component. With the benefit of technological advances, many single-nucleotide polymorphisms (SNPs) have been found to be associated with the risk of complex disorders by using genome wide association studies (GWASs). Disease-associated SNPs are sometimes shared by healthy controls and cannot clearly distinguish affected individuals from unaffected ones. The combined effects of multiple independent SNPs contribute to the disease process, but revealing the relationship between genotype and phenotype based on the combinations remains a great challenge. In this study, by considering the disease prevalence rate, we conducted an exhaustive process to identify whether a genotype combination pattern would have a decisive effect on complex disorders. Based on genotype data for 68 reported SNPs in 8,372 psoriasis patients and 8,510 healthy controls, we found that putative causal genotype combination patterns (CGCPs) were only present in psoriasis patients, not in healthy subjects. These results suggested that psoriasis might be contributed by combined genotypes, complementing the traditional modest susceptibility of a single variant in a single gene for a complex disease. This work is the first systematic study to analyze genotype combinations based on the reported susceptibility genes, considering each individual among the cases and controls from the Chinese population, and could potentially advance disease-gene mapping and precision medicine due to the causality relationship between the candidate CGCPs and complex diseases.

MeSH terms

  • Adult
  • Algorithms*
  • Alleles
  • Chromosomes, Human / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Genotyping Techniques
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • Psoriasis / genetics*
  • Surveys and Questionnaires

Grants and funding

This work was supported by the Key Program of the National Natural Science Foundation of China (81130031), Youth Fund of the First Affiliated Hospital of Anhui Medical University (2010KJ11) and the Natural Science Foundation of Anhui province (1708085QH211). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.