PT - JOURNAL ARTICLE AU - Can Cenik AU - Elif Sarinay Cenik AU - Gun W. Byeon AU - Fabian Grubert AU - Sophie I Candille AU - Damek Spacek AU - Bilal Alsallakh AU - Hagen Tilgner AU - Carlos L. Araya AU - Hua Tang AU - Emiliano Ricci AU - Michael P. Snyder TI - Integrative analysis of RNA, translation and protein levels reveals distinct regulatory variation across humans AID - 10.1101/018572 DP - 2015 Jan 01 TA - bioRxiv PG - 018572 4099 - http://biorxiv.org/content/early/2015/04/26/018572.short 4100 - http://biorxiv.org/content/early/2015/04/26/018572.full AB - Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy - many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation.