In Cell genomics
Understanding the consequences of individual transcriptome variation is fundamental to deciphering human biology and disease. We implement a statistical framework to quantify the contributions of 21 individual traits as drivers of gene expression and alternative splicing variation across 46 human tissues and 781 individuals from the Genotype-Tissue Expression project. We demonstrate that ancestry, sex, age, and BMI make additive and tissue-specific contributions to expression variability, whereas interactions are rare. Variation in splicing is dominated by ancestry and is under genetic control in most tissues, with ribosomal proteins showing a strong enrichment of tissue-shared splicing events. Our analyses reveal a systemic contribution of types 1 and 2 diabetes to tissue transcriptome variation with the strongest signal in the nerve, where histopathology image analysis identifies novel genes related to diabetic neuropathy. Our multi-tissue and multi-trait approach provides an extensive characterization of the main drivers of human transcriptome variation in health and disease.
García-Pérez Raquel, Ramirez Jose Miguel, Ripoll-Cladellas Aida, Chazarra-Gil Ruben, Oliveros Winona, Soldatkina Oleksandra, Bosio Mattia, Rognon Paul Joris, Capella-Gutierrez Salvador, Calvo Miquel, Reverter Ferran, Guigó Roderic, Aguet François, Ferreira Pedro G, Ardlie Kristin G, Melé Marta
2023-Jan-11
BMI, age, alternative splicing, ancestry, diabetes, gene expression, human traits, sex, tissue, transcriptome
