7 research outputs found
Genotype combination contributes to psoriasis: An exhaustive algorithm perspective
<div><p>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.</p></div
The 51 SNPs and alleles associated with psoriasis in the autosomal chromosome.
<p>The outmost lines with different colors represent chromosomes labled by 1–22, and ribbon colors in chromosomes assigned to Giemsa stain based on the color scheme of the UCSC genome browser represent chromosome bands.</p
The toppest candidate CGCP results for three, four and five SNPs and corresponding number of psoriasis patients.
<p>The toppest candidate CGCP results for three, four and five SNPs and corresponding number of psoriasis patients.</p
Distribution of permuted number of patients with the candidate CGCP in every 1000 cases.
<p>The arrow shows the observed number of individuals with the toppest candidate CGCP for three (A), four (B) and five (C) SNPs in the 1000 cases.</p
Frequency of genotype combination patterns for three, four and five SNPs in inverse analysis.
<p>Frequency of genotype combination patterns for three, four and five SNPs in inverse analysis.</p
Protein–protein interaction network of the genes at the loci of the 5 SNPs for the top CGCP.
<p>Text in red, pink, blue, green and black represents genes at the loci of the 5 SNPs rs10852936, rs2233278, rs4561177, rs6590334 and rs7552167, respectively.</p