Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also 34Department of Operations Research and Financial Engineering, Princeton University, Princeton, New Jersey 84540, USA. 35Biomedical Informatics Program, Stanford University, Stanford, California 94305, USA. 36Department of Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Korea. 37Department of Human Genetics, University of California, Los Angeles, California 90095, USA. 38Department of Biology, Stanford University, Stanford, California 94305, USA. 39Department of Computer Science, University of California, Los Angeles, California 90095, USA. 40Computational Biology and Bioinformatics Graduate Program, Duke University, Durham, North Carolina 27708, USA. 41Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, North Carolina 27599, USA. 42Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. 43Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, Massachusetts 02139, USA. 44Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. 45Center for Biomarker Research and Personalized Medicine, Virginia Commonwealth University, Richmond, Virginia 23298, USA. 46Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California 90095, USA. 47Bioinformatics Research Center and Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA. 48Department of Biomedical Data Science, Stanford University, Stanford, California 94305, USA. 49Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK. 50Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK. 51Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford OX3 7LE, UK. 52Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. 53Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA. 54Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York 10032, USA. 55Department of Statistics, Stanford University, Stanford, California 94305, USA. 56Section of Genetic Medicine, Department of Medicine, Institute for Genomics and Systems Biology, Center for Data Intensive Science, University of Chicago, Chicago, Illinois 60637, USA. 57Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA. 58Bioinformatics Research Center, Departments of Statistics and Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA. 59Department of Computer Science and Center for Statistics and Machine Learning, Princeton University, Princeton, New Jersey 08540, USA. *These authors contributed equally to this work. §These authors jointly supervised this work. Online Content Methods, along with any additional Extended Data display items and Source Data, are available in the online version of the paper; references unique to these sections appear only in the online paper. Supplementary Information is available in the online version of the paper. Author Contributions All authors reviewed and revised the manuscript. Detailed author contributions are available in the Supplementary Information. The authors declare competing financial interests: details are available in the online version of the paper. Readers are welcome to comment on the online version of the paper. Page 2 Nature. Author manuscript; available in PMC 2018 January 22. A uhor M anscript