title: A multi-trait, meta-analysis for detecting pleiotropic polymorphisms for stature, fatness and reproduction in beef cattle.
abstract: Polymorphisms that affect complex traits or quantitative trait loci (QTL) often affect multiple traits. We describe two novel methods (1) for finding single nucleotide polymorphisms (SNPs) significantly associated with one or more traits using a multi-trait, meta-analysis, and (2) for distinguishing between a single pleiotropic QTL and multiple linked QTL. The meta-analysis uses the effect of each SNP on each of n traits, estimated in single trait genome wide association studies (GWAS). These effects are expressed as a vector of signed t-values (t) and the error covariance matrix of these t values is approximated by the correlation matrix of t-values among the traits calculated across the SNP (V). Consequently, t'V-1t is approximately distributed as a chi-squared with n degrees of freedom. An attractive feature of the meta-analysis is that it uses estimated effects of SNPs from single trait GWAS, so it can be applied to published data where individual records are not available. We demonstrate that the multi-trait method can be used to increase the power (numbers of SNPs validated in an independent population) of GWAS in a beef cattle data set including 10,191 animals genotyped for 729,068 SNPs with 32 traits recorded, including growth and reproduction traits. We can distinguish between a single pleiotropic QTL and multiple linked QTL because multiple SNPs tagging the same QTL show the same pattern of effects across traits. We confirm this finding by demonstrating that when one SNP is included in the statistical model the other SNPs have a non-significant effect. In the beef cattle data set, cluster analysis yielded four groups of QTL with similar patterns of effects across traits within a group. A linear index was used to validate SNPs having effects on multiple traits and to identify additional SNPs belonging to these four groups.
authors.affiliation: Victorian Department of Environment and Primary Industries, Bundoora, Victoria, Australia.
authors.forename: Sunduimijid
authors.initials: S
authors.lastname: Bolormaa
authors.affiliation: Victorian Department of Environment and Primary Industries, Bundoora, Victoria, Australia.
authors.forename: Jennie E
authors.initials: JE
authors.lastname: Pryce
authors.affiliation: CSIRO Animal, Food and Health Sciences, Queensland Bioscience Precinct, St. Lucia, Queensland, Australia.
authors.forename: Antonio
authors.initials: A
authors.lastname: Reverter
authors.affiliation: Animal Genetics and Breeding Unit, University of New England, Armidale, New South Wales, Australia.
authors.forename: Yuandan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: CSIRO Animal, Food and Health Sciences, Queensland Bioscience Precinct, St. Lucia, Queensland, Australia.
authors.forename: William
authors.initials: W
authors.lastname: Barendse
authors.affiliation: School of Land and Environment, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Kemper
authors.affiliation: Animal Genetics and Breeding Unit, University of New England, Armidale, New South Wales, Australia.
authors.forename: Bruce
authors.initials: B
authors.lastname: Tier
authors.affiliation: Victorian Department of Environment and Primary Industries, Bundoora, Victoria, Australia.
authors.forename: Keith
authors.initials: K
authors.lastname: Savin
authors.affiliation: Victorian Department of Environment and Primary Industries, Bundoora, Victoria, Australia.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Hayes
authors.affiliation: Victorian Department of Environment and Primary Industries, Bundoora, Victoria, Australia; School of Land and Environment, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Goddard
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D055106:Genome-Wide Association Study; D005838:Genotype; D008460:Meat; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D012098:Reproduction / Q000235:genetics*