title: Exome localization of complex disease association signals.
abstract: BACKGROUND
  Genome-wide association studies (GWAS) of common diseases have had a tremendous impact on genetic research over the last five years; the field is now moving from microarray-based technology towards next-generation sequencing. To evaluate the potential of association studies for complex diseases based on exome sequencing we analysed the distribution of association signal with respect to protein-coding genes based on GWAS data for seven diseases from the Wellcome Trust Case Control Consortium.
  
  
  RESULTS
  We find significant concentration of association signal in exons and genes for Crohn's Disease, Type 1 Diabetes and Bipolar Disorder, but also observe enrichment from up to 40 kilobases upstream to 40 kilobases downstream of protein-coding genes for Crohn's Disease and Type 1 Diabetes; the exact extent of the distribution is disease dependent.
  
  
  CONCLUSIONS
  Our work suggests that exome sequencing may be a feasible approach to find genetic variation associated with complex disease. Extending the exome sequencing to include flanking regions therefore promises further improvement of covering disease-relevant variants.
authors.affiliation: King's College London, Department of Medical and Molecular Genetics, 8th floor Tower Wing, Guy's Hospital, London SE19RT, UK.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lehne
authors.forename: Cathryn M
authors.initials: CM
authors.lastname: Lewis
authors.forename: Thomas
authors.initials: T
authors.lastname: Schlitt
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005091:Exons; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide