2026-04-13T02:09:55Zhttps://recercat.cat/oai/request

oai:recercat.cat:10230/558232025-12-12T03:04:27Zcom_2072_6col_2072_452952

00925njm 22002777a 4500 dc García Pérez, Raquel, 1989- author Ramirez, Jose Miguel author Ripoll Cladellas, Aida author Chazarra-Gil, Ruben author Oliveros, Winona author Soldatkina, Oleksandra author Bosio, Mattia author Rognon, Paul Joris author Capella Gutiérrez, Salvador Jesús, 1985- author Calvo, Miquel (Calvo Llorca) author Reverter Comes, Ferran author Guigó Serra, Roderic author Aguet, François author Ferreira, Pedro G. author Ardlie, Kristin G. author Melé Messeguer, Marta, 1982- author 2023-02-20T07:16:21Z 2023-02-20T07:16:21Z 2022 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. This study was funded by the HumTranscriptom project with reference PID2019-107937GA-I00. R.G.-P. was supported by a Juan de la Cierva fellowship (FJC2020-044119-I) funded by MCIN/AEI/10.13039/501100011033 and “European Union NextGenerationEU/PRTR.” J.M.R. was supported by a predoctoral fellowship from “la Caixa” Foundation (ID 100010434) with code LCF/BQ/DR22/11950022. A.R.-C. was supported by a Formación Personal Investigador (FPI) fellowship (PRE2019-090193) funded by MCIN/AEI. R.C.-G. was supported by an FPI fellowship (PRE2020-092510) funded by MCIN/AEI. M.M. was supported by a Ramon y Cajal fellowship (RYC-2017-22249). Figures 4A and S1A and the graphical abstract were created with BioRender.com. We thank the donors and their families for their generous gifts of organ donation for transplantation and tissue donations for the GTEx research project and the GTEx consortium members. BMI Age Alternative splicing Ancestry Diabetes Gene expression Human traits Sex Tissue Transcriptome The landscape of expression and alternative splicing variation across human traits