Upstream ORFs (uORFs) are major cis regulatory elements of translation located in 5? leader sequences of protein-coding mRNAs , and genetic variants interfering with these elements can affect the efficiency of mRNA translation . Out of over a thousand newly detected uORFs per tissue (Additional file 1: Figure S1H and Additional file 4: Table S3), we detected 27 (heart) and 13 (liver) uORFs whose translation rates associated with genetic variants in cis (“uORF-QTLs;” Additional file 4: Table S3). However, none of these variants disrupted the uORF’s start or stop codon, and only a single uORF-QTL mapped to a gene with a primary ORF teQTL. For this gene, Rte1, both QTLs showed the same effect directionality, indicating that increased translation of the uORF had no negative impact on the primary ORF TE (Additional file 1: Figure S2E). In general, uORF and primary ORF translation rates showed a very limited quantitative dependency (as observed in [31, 34,35,36]) (Additional file 4: Table S3, Additional file 1: Figure S2F + G) and we found no enrichment of uORFs in genes with local teQTLs (pheart = 0.70 and pliver = 0.79). In addition, we found no genetic variants in genes with local teQTLs that interfered with local translation initiation context or Kozak sequence, although effects may have been too subtle to detect. Similarly, we could not determine the possible outcome of genetic variants in other functional elements that serve to fine-tune mRNA translation, such as RNA folding structures, methylation sites, or RNA-binding protein motifs [37, 38]bined, our observations imply that uORFs are unlikely to be main drivers of local teQTLs within the HXB/BXH panel.