The availability of high-density SNP assays including the BovineSNP50 (50K) enables the identification of novel quantitative trait loci (QTL) and improvement of the resolution of the locations of previously mapped QTL. We performed a series of genome-wide association studies (GWAS) using 50K genotypes scored in 18,274 animals from 10 US beef cattle breeds with observations for twelve body weights, calving ease and carcass traits. A total of 159 unique large-effect QTL (defined as 1-Mb genome windows explaining more than 1 % of additive genetic variance) were identified. In general, more QTL were identified in analyses with bigger sample sizes. Four large-effect pleiotropic QTLs located on BTA6 at 37 - 42Mb (primarily at 38 Mb), on BTA7 at 93 Mb, on BTA14 at 23 - 26 Mb (primarily at 25 Mb) and on BTA20 at 4 Mb were identified in more than one breed. Several breed-specific large-effect pleiotropic QTL were also identified. This largest GWAS ever performed in beef cattle, led us to discover several novel across-breed and breed-specific pleiotropic or closely linked QTL that cumulatively account for a significant percentage of additive genetic variance (e.g. more than a third of additive genetic variance of birth and mature weights; and calving ease direct in Hereford). Some identified QTL or closely linked regions harbor genes known to have large effects on a variety of traits in cattle such as PLAG1 and MSTN and others harbor promising candidate genes including NCAPG, ARRDC3, ERGIC1, SH3PXD2B, HMGA2, MSRB3, LEMD3, TIGAR, SEPT7, and KIRREL3. Gene ontology analysis revealed that genes involved in ossification and in adipose tissue development were over-represented in the identified leiotropic QTL. Also, the MAPK signaling pathway was identified as a common pathway affected by the genes located near the pleiotropic or closely linked QTL. These results will improve our understanding of the biology of growth and body composition in cattle.