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

Genotype combination contributes to psoriasis: An exhaustive algorithm perspective.

Dou J1,2, Guo H1,2, Cheng F1,2, Huang H1,2, Fu L1,2, Li L3, Yang C1,2, Ye L1,2, Wen L1,2, Cheng Y1,2, Tang L1,2, Zhu C1,2, Zhu Z1,2, Wang W1,2, Sheng Y1,2, Wang Z1,2, Liu S1,2, Fan X1,2, Zuo X1,2, Zhou F1,2, Sun L1,2, Zheng X1,2, Zhang X1,2.

Author information

1
Institute of Dermatology and Department of Dermatology at No. 1 Hospital, Anhui Medical University, Hefei, China.
2
Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei, China.
3
The Department of Dermatology, The First Affiliated Hospital, Gannan Medical University, Ganzhou, China.

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.

PMID:
29020033
PMCID:
PMC5636117
DOI:
10.1371/journal.pone.0186067
[Indexed for MEDLINE]
Free PMC Article

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