title: Look beyond one's own nose: combination of information from publicly available sources reveals an association of GATA4 polymorphisms with plasma triglycerides.
abstract: OBJECTIVE
  GATA4iKO mice exhibit impeded triglyceride absorption from intestine and decreased plasma triglyceride levels. Data in humans are lacking. We hypothesized that triglyceride levels might also be regulated by polymorphisms in the GATA4 gene in humans. We used publicly available data from different sources to evaluate this hypothesis. Our approach is a more often applicable advance to uncover associations and their functional implications which would have been otherwise missed by standard genome-wide association studies (GWAS).
  
  
  METHODS
  We used the publicly available GWAS results from 137 SNPs in the GATA4 region for triglyceride levels. We embedded these results into the comprehensive functional genomics data provided in the UCSC Genome Browser including among others information on regulatory elements and interspecies conservation. A concise graphical presentation is proposed together with an R function for automatic data preparation. This process is presented in an educational manner using a screencast to become most useful for other researchers.
  
  
  RESULTS
  We observed several polymorphisms in and around the GATA4 gene which have a significant influence on plasma triglyceride levels with the lowest p-value at SNP rs1466785 (Bonferroni-corrected p-value = 1.76e-5). The bioinformatic evaluation of this locus in publicly available functional genomics data provided converging evidence for the presence of a transcriptional regulator downstream of GATA4.
  
  
  CONCLUSIONS
  The combination of different sources of data has revealed an association of GATA4 with triglyceride levels in humans. Our evaluation exemplifies how an integrative analysis including both statistical and biological perspectives can shed new light on available association data and reveals novel candidate genes, which are otherwise hidden in the noisy region below genome-wide significance.
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lamina
authors.forename: Stefan
authors.initials: S
authors.lastname: Coassin
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
mesh_terms: D022126:Access to Information; D019295:Computational Biology; D057225:Data Mining; D030541:Databases, Genetic; D019317:Evidence-Based Medicine; D050991:GATA4 Transcription Factor / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D014280:Triglycerides / Q000097:blood*
chemical_list: D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D014280:Triglycerides