Prediction of Disease and Phenotype Associations from Genome-Wide Association Studies 英文参考文献.docVIP

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Prediction of Disease and Phenotype Associations from Genome-Wide Association Studies 英文参考文献.doc

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Prediction of Disease and Phenotype Associations from Genome-Wide Association Studies 英文参考文献

PredictionofDiseaseandPhenotypeAssociationsfrom Genome-WideAssociationStudies StephanieN.Lewis1,2,ElaineNsoesie1,CharlesWeeks1,DanQiao3,LiqingZhang1,3* 1Genetics,Bioinformatics,andComputationalBiologyProgram,VirginiaTech,Blacksburg,Virginia,UnitedStatesofAmerica,2DepartmentofBiochemistry,VirginiaTech, Blacksburg,Virginia,UnitedStatesofAmerica,3DepartmentofComputerScience,VirginiaTech,Blacksburg,Virginia,UnitedStatesofAmerica Abstract Background:Genomewideassociationstudies(GWAS)haveprovenusefulasamethodforidentifyinggeneticvariations associated with diseases. In this study, we analyzed GWAS data for 61 diseases and phenotypes to elucidate common associations based on single nucleotide polymorphisms (SNP). The study was an expansion on a previous study on identifyingdiseaseassociationsviadatafromasingleGWASonsevendiseases. Methodology/Principal Findings: Adjustments to the originally reported study included expansion of the SNP dataset usingLinkageDisequilibrium(LD)andrefinementofthefourlevelsofanalysistoencompassSNP,SNPblock,gene,and pathwaylevelcomparisons.Apair-wisecomparisonbetweendiseasesandphenotypeswasperformedateachlevelandthe Jaccard similarity index was used to measure the degree of association between two diseases/phenotypes. Disease relatedness networks (DRNs) were used to visualize our results. We saw predominant relatedness between Multiple Sclerosis,type1diabetes,andrheumatoidarthritisforthefirstthreelevelsofanalysis.Expectedrelatednesswasalsoseen betweenlipid-andblood-relatedtraits. Conclusions/Significance: The predominant associations between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritiscanbevalidatedbyclinicalstudies.Thediseaseshavebeenproposedtoshareasystemicinflammationphenotype that can result in progression of additional diseases in patients with one of these three diseases. We also noticed unexpected relationships between metabolic and neurological diseases at the pathway comparison level. The less significant relationships f