A combined strategy for quantitative trait loci detection by genome-wide association.
BACKGROUND
We applied a range of genome-wide association (GWA) methods to map quantitative trait loci (QTL) in the simulated dataset provided by the 12th QTLMAS workshop in order to derive an effective strategy.


RESULTS
A variance component linkage analysis revealed QTLs but with low resolution. Three single-marker based GWA methods were then applied: Transmission Disequilibrium Test and single marker regression, fitting an additive model or a genotype model, on phenotypes pre-corrected for pedigree and fixed effects. These methods detected QTL positions with high concordance to each other and with greater refinement of the linkage signals. Further multiple-marker and haplotype analyses confirmed the results with higher significance. Two-locus interaction analysis detected two epistatic pairs of markers that were not significant by marginal effects. Overall, using stringent Bonferroni thresholds we identified 9 additive QTL and 2 epistatic interactions, which together explained about 12.3% of the corrected phenotypic variance.


CONCLUSIONS
The combination of methods that are robust against population stratification, like QTDT, with flexible linear models that take account of the family structure provided consistent results. Extensive simulations are still required to determine appropriate thresholds for more advanced model including epistasis.
Lam
Alex C
AC
Division of Genetics and Genomics, Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, EH25 9PS, UK.|Institute of Evolutionary Biology, Ashworth Laboratories, Kings Buildings, University of Edinburgh, Edinburgh, EH9 3JT, UK.
Powell
Joseph
J
Division of Genetics and Genomics, Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, EH25 9PS, UK.|Institute of Evolutionary Biology, Ashworth Laboratories, Kings Buildings, University of Edinburgh, Edinburgh, EH9 3JT, UK.
Wei
Wen-Hua
WH
Division of Genetics and Genomics, Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, EH25 9PS, UK.
de Koning
Dirk-Jan
DJ
Division of Genetics and Genomics, Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, EH25 9PS, UK.
Haley
Chris S
CS
Division of Genetics and Genomics, Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, EH25 9PS, UK.|MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK.