Genome-wide genetic association of complex traits in heterogeneous stock mice.
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.
Valdar
William
W
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Solberg
Leah C
LC
Gauguier
Dominique
D
Burnett
Stephanie
S
Klenerman
Paul
P
Cookson
William O
WO
Taylor
Martin S
MS
Rawlins
J Nicholas P
JN
Mott
Richard
R
Flint
Jonathan
J
D000818:Animals; D001947:Breeding; D002874:Chromosome Mapping; D005260:Female; D023281:Genomics; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice / Q000235:genetics*; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci