Efficient Strategy to Identify Gene-Gene Interactions and Its Application to Type 2 Diabetes

Over the past decade, the detection of gene-gene interactions has become more and more popular in the field of genome-wide association studies (GWASs). The goal of the GWAS is to identify genetic susceptibility to complex diseases by assaying and analyzing hundreds of thousands of single-nucleotide...

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Main Authors: Donghe Li, Sungho Won
Format: Article
Language:English
Published: BioMed Central 2016-12-01
Series:Genomics & Informatics
Subjects:
Online Access:http://genominfo.org/upload/pdf/gni-14-160.pdf
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author Donghe Li
Sungho Won
author_facet Donghe Li
Sungho Won
author_sort Donghe Li
collection DOAJ
description Over the past decade, the detection of gene-gene interactions has become more and more popular in the field of genome-wide association studies (GWASs). The goal of the GWAS is to identify genetic susceptibility to complex diseases by assaying and analyzing hundreds of thousands of single-nucleotide polymorphisms. However, such tests are computationally demanding and methodologically challenging. Recently, a simple but powerful method, named “BOolean Operation-based Screening and Testing” (BOOST), was proposed for genome-wide gene-gene interaction analyses. BOOST was designed with a Boolean representation of genotype data and is approximately equivalent to the log-linear model. It is extremely fast, and genome-wide gene-gene interaction analyses can be completed within a few hours. However, BOOST can not adjust for covariate effects, and its type-1 error control is not correct. Thus, we considered two-step approaches for gene-gene interaction analyses. First, we selected gene-gene interactions with BOOST and applied logistic regression with covariate adjustments to select gene-gene interactions. We applied the two-step approach to type 2 diabetes (T2D) in the Korea Association Resource (KARE) cohort and identified some promising pairs of single-nucleotide polymorphisms associated with T2D.
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spelling doaj-art-776cb3fbdf0e42f6931002bc668b51f22025-02-02T04:35:58ZengBioMed CentralGenomics & Informatics1598-866X2234-07422016-12-0114416016510.5808/GI.2016.14.4.160172Efficient Strategy to Identify Gene-Gene Interactions and Its Application to Type 2 DiabetesDonghe Li0Sungho Won1Interdisciplinary Program of Bioinformatics, Seoul National University, Seoul 08826, Korea.Interdisciplinary Program of Bioinformatics, Seoul National University, Seoul 08826, Korea.Over the past decade, the detection of gene-gene interactions has become more and more popular in the field of genome-wide association studies (GWASs). The goal of the GWAS is to identify genetic susceptibility to complex diseases by assaying and analyzing hundreds of thousands of single-nucleotide polymorphisms. However, such tests are computationally demanding and methodologically challenging. Recently, a simple but powerful method, named “BOolean Operation-based Screening and Testing” (BOOST), was proposed for genome-wide gene-gene interaction analyses. BOOST was designed with a Boolean representation of genotype data and is approximately equivalent to the log-linear model. It is extremely fast, and genome-wide gene-gene interaction analyses can be completed within a few hours. However, BOOST can not adjust for covariate effects, and its type-1 error control is not correct. Thus, we considered two-step approaches for gene-gene interaction analyses. First, we selected gene-gene interactions with BOOST and applied logistic regression with covariate adjustments to select gene-gene interactions. We applied the two-step approach to type 2 diabetes (T2D) in the Korea Association Resource (KARE) cohort and identified some promising pairs of single-nucleotide polymorphisms associated with T2D.http://genominfo.org/upload/pdf/gni-14-160.pdfepistasisgene-gene interactiongenome-wide association studytype 2 diabetes mellitus
spellingShingle Donghe Li
Sungho Won
Efficient Strategy to Identify Gene-Gene Interactions and Its Application to Type 2 Diabetes
Genomics & Informatics
epistasis
gene-gene interaction
genome-wide association study
type 2 diabetes mellitus
title Efficient Strategy to Identify Gene-Gene Interactions and Its Application to Type 2 Diabetes
title_full Efficient Strategy to Identify Gene-Gene Interactions and Its Application to Type 2 Diabetes
title_fullStr Efficient Strategy to Identify Gene-Gene Interactions and Its Application to Type 2 Diabetes
title_full_unstemmed Efficient Strategy to Identify Gene-Gene Interactions and Its Application to Type 2 Diabetes
title_short Efficient Strategy to Identify Gene-Gene Interactions and Its Application to Type 2 Diabetes
title_sort efficient strategy to identify gene gene interactions and its application to type 2 diabetes
topic epistasis
gene-gene interaction
genome-wide association study
type 2 diabetes mellitus
url http://genominfo.org/upload/pdf/gni-14-160.pdf
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AT sunghowon efficientstrategytoidentifygenegeneinteractionsanditsapplicationtotype2diabetes