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Open Access Highly Accessed Research article

Exome localization of complex disease association signals

Benjamin Lehne1, Cathryn M Lewis12 and Thomas Schlitt1*

Author Affiliations

1 King's College London, Department of Medical and Molecular Genetics, 8th floor Tower Wing, Guy's Hospital, London SE1 9RT, UK

2 King's College London, MRC SGDP Centre, Institute of Psychiatry, de Crespigny Park, London SE5 8AF, UK

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BMC Genomics 2011, 12:92  doi:10.1186/1471-2164-12-92

Published: 1 February 2011



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.


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.


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.