Cell type–specific genetic regulation of gene expression across human tissues-Reference-Cited by-同舟云学术

Cell type–specific genetic regulation of gene expression across human tissues

Published:2020-09-10 Issue:6509 Volume:369 Page:eaaz8528
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Kim-Hellmuth Sarah¹²³^ORCID,Aguet François⁴^ORCID,Oliva Meritxell⁵⁶^ORCID,Muñoz-Aguirre Manuel⁷⁸^ORCID,Kasela Silva²³^ORCID,Wucher Valentin⁷^ORCID,Castel Stephane E.²³^ORCID,Hamel Andrew R.⁴⁹^ORCID,Viñuela Ana¹⁰¹¹¹²¹³^ORCID,Roberts Amy L.¹⁰^ORCID,Mangul Serghei¹⁴¹⁵^ORCID,Wen Xiaoquan¹⁶,Wang Gao¹⁷^ORCID,Barbeira Alvaro N.⁵^ORCID,Garrido-Martín Diego⁷^ORCID,Nadel Brian B.¹⁸^ORCID,Zou Yuxin¹⁹^ORCID,Bonazzola Rodrigo⁵^ORCID,Quan Jie²⁰^ORCID,Brown Andrew¹¹²¹^ORCID,Martinez-Perez Angel²²^ORCID,Soria José Manuel²²,Getz Gad⁴²³²⁴^ORCID,Dermitzakis Emmanouil T.¹¹¹²¹³^ORCID,Small Kerrin S.¹⁰^ORCID,Stephens Matthew¹⁷^ORCID,Xi Hualin S.²⁵^ORCID,Im Hae Kyung⁵^ORCID,Guigó Roderic⁷²⁶^ORCID,Segrè Ayellet V.⁴⁹^ORCID,Stranger Barbara E.⁵²⁷^ORCID,Ardlie Kristin G.⁴^ORCID,Lappalainen Tuuli²³^ORCID,

Affiliation:

1. Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany.

2. New York Genome Center, New York, NY, USA.

3. Department of Systems Biology, Columbia University, New York, NY, USA.

4. The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

5. Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.

6. Department of Public Health Sciences, University of Chicago, Chicago, IL, USA.

7. Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Barcelona, Catalonia, Spain.

8. Department of Statistics and Operations Research, Universitat Politècnica de Catalunya (UPC), Barcelona, Catalonia, Spain.

9. Ocular Genomics Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.

10. Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK.

11. Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.

12. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland.

13. Swiss Institute of Bioinformatics, Geneva, Switzerland.

14. Department of Computer Science, University of California, Los Angeles, Los Angeles, CA, USA.

15. Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, Los Angeles, CA, USA.

16. Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.

17. Department of Human Genetics, University of Chicago, Chicago, IL, USA.

18. Department of Molecular, Cellular, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.

19. Department of Statistics, University of Chicago, Chicago, IL, USA.

20. Inflammation & Immunology, Pfizer, Cambridge, MA, USA.

21. Population Health and Genomics, University of Dundee, Dundee, Scotland, UK.

22. Unit of Genomic of Complex Diseases, Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain.

23. Cancer Center and Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.

24. Harvard Medical School, Boston, MA, USA.

25. Foundational Neuroscience Center, AbbVie, Cambridge, MA, USA.

26. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.

27. Center for Genetic Medicine, Department of Pharmacology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.

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.

Funder

NIH Office of the Director

European Commission

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference61 articles.

1. The GTEx Consortium atlas of genetic regulatory effects across human tissues

2. Unraveling the polygenic architecture of complex traits using blood eQTL metaanalysis

3. Integrated genome-wide analysis of expression quantitative trait loci aids interpretation of genomic association studies

4. Dissecting the genetics of the human transcriptome identifies novel trait-relatedtrans-eQTLs and corroborates the regulatory relevance of non-protein coding loci

5. Gene-gene and gene-environment interactions detected by transcriptome sequence analysis in twins

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