한빛사 논문
Max Planck Institute of Psychiatry, New York Genome Center, Columbia University
Sarah Kim-Hellmuth1,2,3,*,†,‡, François Aguet4,†, Meritxell Oliva5,6, Manuel Muñoz-Aguirre7,8, Silva Kasela2,3, Valentin Wucher7, Stephane E. Castel2,3, Andrew R. Hamel4,9, Ana Viñuela10,11,12,13, Amy L. Roberts10, Serghei Mangul14,15, Xiaoquan Wen16, Gao Wang17, Alvaro N. Barbeira5, Diego Garrido-Martín7, Brian B. Nadel18, Yuxin Zou19, Rodrigo Bonazzola5, Jie Quan20, Andrew Brown11,21, Angel Martinez-Perez22, José Manuel Soria22, GTEx Consortium§, Gad Getz4,23,24, Emmanouil T. Dermitzakis11,12,13, Kerrin S. Small10, Matthew Stephens17, Hualin S. Xi25, Hae Kyung Im5, Roderic Guigó7,26, Ayellet V. Segrè4,9, Barbara E. Stranger5,27, Kristin G. Ardlie4, Tuuli Lappalainen2,3,*
1Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany.
2New York Genome Center, New York, NY, USA.
3Department of Systems Biology, Columbia University, New York, NY, USA.
4The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
5Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.
6Department of Public Health Sciences, University of Chicago, Chicago, IL, USA.
7Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Barcelona, Catalonia, Spain.
8Department of Statistics and Operations Research, Universitat Politècnica de Catalunya (UPC), Barcelona, Catalonia, Spain.
9Ocular Genomics Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.
10Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK.
11Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
12Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland.
13Swiss Institute of Bioinformatics, Geneva, Switzerland.
14Department of Computer Science, University of California, Los Angeles, Los Angeles, CA, USA.
15Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, Los Angeles, CA, USA.
16Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
17Department of Human Genetics, University of Chicago, Chicago, IL, USA.
18Department of Molecular, Cellular, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
19Department of Statistics, University of Chicago, Chicago, IL, USA.
20Inflammation & Immunology, Pfizer, Cambridge, MA, USA.
21Population Health and Genomics, University of Dundee, Dundee, Scotland, UK.
22Unit of Genomic of Complex Diseases, Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain.
23Cancer Center and Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
24Harvard Medical School, Boston, MA, USA.
25Foundational Neuroscience Center, AbbVie, Cambridge, MA, USA.
26Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
27Center for Genetic Medicine, Department of Pharmacology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
*Corresponding author.
† These authors contributed equally to this work.
‡ Present address: Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital LMU Munich, Munich, Germany.
§ A full list of the GTEx authors and their affiliations is available at the end of this article.
Abstract
The Genotype-Tissue Expression (GTEx) project has identified expression and splicing quantitative trait loci in cis (QTLs) for the majority of genes across a wide range of human tissues. However, the functional characterization of these QTLs has been limited by the heterogeneous cellular composition of GTEx tissue samples. We mapped interactions between computational estimates of cell type abundance and genotype to identify cell type–interaction QTLs for seven cell types and show that cell type–interaction expression QTLs (eQTLs) provide finer resolution to tissue specificity than bulk tissue cis-eQTLs. Analyses of genetic associations with 87 complex traits show a contribution from cell type–interaction QTLs and enables the discovery of hundreds of previously unidentified colocalized loci that are masked in bulk tissue.
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