title: Prediction of disease and phenotype associations from genome-wide association studies.
abstract: BACKGROUND
  Genome wide association studies (GWAS) have proven useful as a method for identifying genetic variations 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 identifying disease associations via data from a single GWAS on seven diseases.
  
  
  RESULTS
  Adjustments to the originally reported study included expansion of the SNP dataset using Linkage Disequilibrium (LD) and refinement of the four levels of analysis to encompass SNP, SNP block, gene, and pathway level comparisons. A pair-wise comparison between diseases and phenotypes was performed at each level and the 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, type 1 diabetes, and rheumatoid arthritis for the first three levels of analysis. Expected relatedness was also seen between lipid- and blood-related traits.
  
  
  CONCLUSIONS
  The predominant associations between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis can be validated by clinical studies. The diseases have been proposed to share a systemic inflammation phenotype 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 found between diseases require a more detailed literature review to determine validity of the predictions. The results from this study serve as a first step towards a better understanding of seemingly unrelated diseases and phenotypes with similar symptoms or modes of treatment.
authors.affiliation: Genetics, Bioinformatics, and Computational Biology Program, Virginia Tech, Blacksburg, Virginia, United States of America.
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: Lewis
authors.forename: Elaine
authors.initials: E
authors.lastname: Nsoesie
authors.forename: Charles
authors.initials: C
authors.lastname: Weeks
authors.forename: Dan
authors.initials: D
authors.lastname: Qiao
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhang
mesh_terms: D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000235:genetics; D053263:Gene Regulatory Networks; D005796:Genes / Q000502:physiology; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D015398:Signal Transduction
references.citation: Genome Res. 2004 May;14(5):925-8
references.pmid: 15078858
references.citation: PLoS One. 2011 Jan 05;6(1):e15247
references.pmid: 21245926
references.citation: JAMA. 1979 May 11;241(19):2035-8
references.pmid: 430798
references.citation: Nucleic Acids Res. 2010 Jan;38(Database issue):D355-60
references.pmid: 19880382
references.citation: Nature. 2005 Oct 27;437(7063):1299-320
references.pmid: 16255080
references.citation: Genome Res. 2003 Nov;13(11):2498-504
references.pmid: 14597658
references.citation: Hum Mol Genet. 2009 Oct 15;18(R2):R216-23
references.pmid: 19808799
references.citation: Diabetes. 2002 Jul;51(7):2325-8
references.pmid: 12086969
references.citation: Nat Rev Genet. 2008 May;9(5):356-69
references.pmid: 18398418
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):27-30
references.pmid: 10592173
references.citation: Diabetes Care. 2003 Nov;26(11):3192-3
references.pmid: 14578268
references.citation: Am J Hum Genet. 2010 Jan;86(1):6-22
references.pmid: 20074509
references.citation: J Rheumatol. 2007 Mar;34(3):460-2
references.pmid: 17343298
references.citation: Trends Mol Med. 2002 Aug;8(8):375-84
references.pmid: 12127723
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D354-7
references.pmid: 16381885
references.citation: BMC Genet. 2010 Jun 28;11:56
references.pmid: 20584270
references.citation: Diabetes Care. 1991 Mar;14(3):173-94
references.pmid: 2044434
references.citation: Lancet Neurol. 2008 Nov;7(11):1067-72
references.pmid: 18940696
references.citation: Nat Rev Genet. 2005 Feb;6(2):95-108
references.pmid: 15716906
references.citation: BMC Med Genet. 2009 Jan 22;10:6
references.pmid: 19161620
references.citation: Science. 2001 Feb 16;291(5507):1304-51
references.pmid: 11181995
references.citation: Nature. 2007 Jun 7;447(7145):661-78
references.pmid: 17554300
references.citation: Nature. 2007 Oct 18;449(7164):851-61
references.pmid: 17943122
references.citation: Arch Neurol. 2006 Jul;63(7):1001-4
references.pmid: 16831970
references.citation: Nature. 2001 Feb 15;409(6822):860-921
references.pmid: 11237011
references.citation: JAMA. 2009 Nov 11;302(18):2028-9
references.pmid: 19903925
references.citation: BMC Bioinformatics. 2009 Jan 30;10 Suppl 1:S68
references.pmid: 19208172
references.citation: J Rheumatol. 2006 May;33(5):1027-8
references.pmid: 16541474
references.citation: Proc Natl Acad Sci U S A. 2007 May 22;104(21):8685-90
references.pmid: 17502601