Nature Genetics
- 38, 879 - 887 (2006)
Published online: 9 July 2006; Corrected online: 04 August 2006 | doi:10.1038/ng1840
Genome-wide genetic association of complex traits in heterogeneous stock miceWilliam Valdar1, Leah C Solberg1, 4, Dominique Gauguier1, Stephanie Burnett1, Paul Klenerman2, William O Cookson1, Martin S Taylor1, J Nicholas P Rawlins3, Richard Mott1 & Jonathan Flint11
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK. 2
Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK. 3
Department of Experimental Psychology, University of Oxford, Oxford OX1 3UD, UK. 4
Current address: Medical College of Wisconsin, Human and Molecular Genetics Center (HMGC), 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
Correspondence should be addressed to Jonathan Flint jf@well.ox.ac.uk or Richard Mott rmott@well.ox.ac.uk Difficulties in fine-mapping quantitative trait loci (QTLs) are a major impediment to progress in the molecular dissection of complex traits in mice. Here we show that genome-wide high-resolution mapping of multiple phenotypes can be achieved using a stock of genetically heterogeneous mice. We developed a conservative and robust bootstrap analysis to map 843 QTLs with an average 95% confidence interval of 2.8 Mb. The QTLs contribute to variation in 97 traits, including models of human disease (asthma, type 2 diabetes mellitus, obesity and anxiety) as well as immunological, biochemical and hematological phenotypes. The genetic architecture of almost all phenotypes was complex, with many loci each contributing a small proportion to the total variance. Our data set, freely available at http://gscan.well.ox.ac.uk, provides an entry point to the functional characterization of genes involved in many complex traits.
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