Discovering genetic factors for psoriasis through exhaustively searching for significant second order SNP-SNP interactions

Kwan-Yeung LEE*, Kwong-Sak LEUNG, Nelson L.S. TANG*, Man-Hon WONG

*Corresponding author for this work

Research output: Journal PublicationsJournal Article (refereed)peer-review

17 Citations (Scopus)

Abstract

In this paper, we aim at discovering genetic factors of psoriasis through searching for statistically significant SNP-SNP interactions exhaustively from two real psoriasis genome-wide association study datasets (phs000019.v1.p1 and phs000982.v1.p1) downloaded from the database of Genotypes and Phenotypes. To deal with the enormous search space, our search algorithm is accelerated with eight biological plausible interaction patterns and a pre-computed look-up table. After our search, we have discovered several SNPs having a stronger association to psoriasis when they are in combination with another SNP and these combinations may be non-linear interactions. Among the top 20 SNP-SNP interactions being found in terms of pairwise p-value and improvement metric value, we have discovered 27 novel potential psoriasis-associated SNPs where most of them are reported to be eQTLs of a number of known psoriasis-associated genes. On the other hand, we have inferred a gene network after selecting the top 10000 SNP-SNP interactions in terms of improvement metric value and we have discovered a novel long distance interaction between XXbac-BPG154L12.4 and RNU6-283P which is not a long distance haplotype and may be a new discovery. Finally, our experiments with the synthetic datasets have shown that our pre-computed look-up table technique can significantly speed up the search process.

Original languageEnglish
Article number15186
Number of pages11
JournalScientific Reports
Volume8
Issue number1
Early online date12 Oct 2018
DOIs
Publication statusPublished - 2018
Externally publishedYes

Bibliographical note

Kwan-Yeung Lee conducted the project and developed the the algorithms used in this study under the supervision of Man-Hon Wong and Kwong-Sak Leung and interpreted the biological meaning of the experimental results under the guidance of Nelson L.S. Tang who pioneered the interaction models. Kwan-Yeung Lee also ran the experiments and wrote the main manuscript text. All authors discussed the results and reviewed the manuscript thoroughly.

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