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Stature is affected by many polymorphisms of small effect in humans1. In contrast, variation in dogs, even within breeds, has been suggested to be largely due to variants in a small number of genes2,3. Here we use data from cattle to compare the genetic architecture of stature to those in humans and dogs. We conducted a meta-analysis for stature using 58,265 cattle from 17 populations with 25.4 million imputed whole-genome sequence variants. Results showed that the genetic architecture of stature in cattle is similar to that in humans, as the lead variants in 163 significantly associated genomic regions (P < 5 x 10-8) explained at most 13.8% of the phenotypic variance. Most of these variants were noncoding, including variants that were also expression quantitative trait loci (eQTLs) and in ChIP-seq peaks. There was significant overlap in loci for stature with humans and dogs, suggesting that a set of common genes regulates body size in mammals.
Within each cattle population (Supplementary Table 1), the 1000 Bull Genomes Run4 reference population of 1,147 whole-genomesequenced individuals was used to impute 630,000 SNP genotypes to 25.4 million whole-genome sequence variants4. A genome-wide association study (GWAS) for stature was performed in each population separately (Supplementary Table 1)5,6. Meta-analysis across the populations found genome-wide significant (P < 5 X 10-8) sequence variants in 163 1-Mb regions (Fig. 1). The lead variants (most significant variants in each region) included 160 SNPs and 3 indels (Supplementary Table 2).
Three approaches were used to validate the lead variants. Association of the variants with stature was tested in 30,175 additional cattle with stature phenotypes from ten populations (Supplementary Table 3). In meta- analysis of these validation populations, 20 of 101 SNPs (the lead variants polymorphic in all populations) were validated at P < 0.05, giving a false discovery rate of 25% (Supplementary Table 4). SNPs were also validated within each population, as some variants were polymorphic in one or only a small number of breeds. The majority of variants (53%; 86) were validated in at least one population, and 28 were validated in more than one population (11 expected by chance) (Supplementary Table 4). The lead variants explained between 2.1% (Limousin) and 13.8% (Brown Swiss) of the phenotypic variation in stature (Table...