The impact of sex on gene expression across human tissues-Reference-Cited by-同舟云学术

The impact of sex on gene expression across human tissues

Published:2020-09-10 Issue:6509 Volume:369 Page:eaba3066
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Oliva Meritxell¹²³^ORCID,Muñoz-Aguirre Manuel⁴⁵^ORCID,Kim-Hellmuth Sarah⁶⁷⁸^ORCID,Wucher Valentin⁴^ORCID,Gewirtz Ariel D. H.⁹^ORCID,Cotter Daniel J.¹⁰^ORCID,Parsana Princy¹¹,Kasela Silva⁷⁸^ORCID,Balliu Brunilda¹²^ORCID,Viñuela Ana¹³^ORCID,Castel Stephane E.⁷⁸^ORCID,Mohammadi Pejman¹⁴^ORCID,Aguet François¹⁵^ORCID,Zou Yuxin¹⁶^ORCID,Khramtsova Ekaterina A.¹¹⁷^ORCID,Skol Andrew D.¹²¹⁸¹⁹,Garrido-Martín Diego⁴^ORCID,Reverter Ferran²⁰,Brown Andrew²¹^ORCID,Evans Patrick²²,Gamazon Eric R.²²²³^ORCID,Payne Anthony²⁴,Bonazzola Rodrigo¹^ORCID,Barbeira Alvaro N.¹^ORCID,Hamel Andrew R.¹⁵²⁵^ORCID,Martinez-Perez Angel²⁶^ORCID,Soria José Manuel²⁶,Pierce Brandon L.³^ORCID,Stephens Matthew¹⁶²⁷^ORCID,Eskin Eleazar²⁸,Dermitzakis Emmanouil T.¹³^ORCID,Segrè Ayellet V.¹⁵²⁵^ORCID,Im Hae Kyung¹^ORCID,Engelhardt Barbara E.²⁹³⁰^ORCID,Ardlie Kristin G.¹⁵^ORCID,Montgomery Stephen B.¹⁰³¹^ORCID,Battle Alexis J.¹¹³²^ORCID,Lappalainen Tuuli⁷⁸^ORCID,Guigó Roderic⁴³³^ORCID,Stranger Barbara E.¹²¹⁸³⁴^ORCID,

Affiliation:

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

2. Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL, USA.

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

4. Centre for Genomic Regulation, Barcelona Institute for Science and Technology, Barcelona, Catalonia, Spain.

5. Department of Statistics and Operations Research, Universitat Politècnica de Catalunya, Barcelona, Catalonia, Spain.

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

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

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

9. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.

10. Department of Genetics, Stanford University, Stanford, CA, USA.

11. Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA.

12. Department of Computational Medicine, University of California, Los Angeles, CA, USA.

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

14. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Scripps Research Translational Institute, La Jolla, CA, USA.

15. Broad Institute of MIT and Harvard, Cambridge, MA, USA.

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

17. Computational Sciences, Janssen Pharmaceuticals, Spring House, PA, USA.

18. Center for Translational Data Science, University of Chicago, Chicago, IL, USA.

19. Department of Pathology and Laboratory Medicine, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA.

20. Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Spain.

21. University of Dundee, Dundee, Scotland, UK.

22. Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

23. Clare Hall, University of Cambridge, Cambridge, UK.

24. Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

25. Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.

26. Genomics of Complex Diseases Group, Research Institute Hospital de la Sant Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain.

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

28. Departments of Computational Medicine, Computer Science, and Human Genetics, University of California, Los Angeles, CA, USA.

29. Department of Computer Science, Center for Statistics and Machine Learning, Princeton University, Princeton, NJ, USA.

30. Genomics plc, Oxford, UK.

31. Department of Pathology, Stanford University, Stanford, CA, USA.

32. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.

33. Universitat Pompeu Fabra, Barcelona, Catalonia, Spain.

34. Center for Genetic Medicine, Department of Pharmacology, Northwestern University, Chicago, IL, USA.

Abstract

Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. By integrating sex-biased eQTLs with genome-wide association study data, we identify 58 gene-trait associations that are driven by genetic regulation of gene expression in a single sex. These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference101 articles.

1. Sexual dimorphism in the incidence of human cancers

2. Sex and Racial Differences in Pharmacological Response: Where Is the Evidence? Pharmacogenetics, Pharmacokinetics, and Pharmacodynamics

3. A chronological map of 308 physical and mental health conditions from 4 million individuals in the English National Health Service

4. Gender differences in autoimmune disease

5. Population-wide analysis of differences in disease progression patterns in men and women

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