Cardiometabolic risk loci share downstream cis- and trans-gene regulation across tissues and diseases

Author:

Franzén Oscar12,Ermel Raili34,Cohain Ariella1,Akers Nicholas K.1,Di Narzo Antonio1,Talukdar Husain A.5,Foroughi-Asl Hassan5,Giambartolomei Claudia6,Fullard John F.6,Sukhavasi Katyayani3,Köks Sulev3,Gan Li-Ming7,Giannarelli Chiara18,Kovacic Jason C.8,Betsholtz Christer910,Losic Bojan1,Michoel Tom11,Hao Ke1,Roussos Panos1612,Skogsberg Josefin5,Ruusalepp Arno234,Schadt Eric E.1,Björkegren Johan L. M.1235

Affiliation:

1. Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York , NY 10029, USA.

2. Clinical Gene Networks AB, Jungfrugatan 10, 114 44 Stockholm, Sweden.

3. Department of Pathophysiology, Institute of Biomedicine and Translation Medicine, University of Tartu, Biomeedikum, Ravila 19, 50411, Tartu, Estonia.

4. Department of Cardiac Surgery, Tartu University Hospital, 1a Ludwig Puusepa Street, 50406 Tartu, Estonia.

5. Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles Väg 2, 171 77 Stockholm, Sweden.

6. Division of Psychiatric Genomics, Department of Psychiatry and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York , NY 10029, USA.

7. Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 431 83, Sweden.

8. Cardiovascular Research Center Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York , NY 10029, USA.

9. AstraZeneca-Karolinska Integrated CardioMetabolic Centre (ICMC), Karolinska Institutet, Novum, Blickagången 6, 141 57 Huddinge, Sweden.

10. Department of Immunology, Genetics and Pathology Dag Hammarskjölds Väg 20, 751 85 Uppsala, Sweden.

11. Division of Genetics and Genomics, The Roslin Institute, University of Edinburgh, Old College, South Bridge, Edinburgh EH8 9YL, UK.

12. Department of Psychiatry, J. J. Peters VA Medical Center, Mental Illness Research Education and Clinical Center (MIRECC), 130 West Kingsbridge Road, Bronx, NY 10468, USA.

Abstract

Genetic variation and coronary artery disease Most genetic variants lie outside protein-coding genes, but their effects, especially in human health, are not well understood. Franzén et al. examined gene expression in tissues affected by coronary artery disease (CAD). They found that individuals with loci that have been associated with CAD in genome-wide analyses had different patterns of tissue-specific gene expression than individuals without these genetic variants. Similarly, tissues not associated with CAD did not have CAD-like expression patterns. Thus, tissue-specific data can be used to dissect the genetic effects that predispose individuals to CAD. Science , this issue p. 827

Funder

University of Tartu

Estonian Research Council

Astra-Zeneca Translational Science Centre-Karolinska Institutet

Torsten and Ragnar Söderberg Foundation

Knut and Alice Wallenberg Foundation

American Heart Association

National Institutes of Health

NIH NHLBI

Veterans Affairs

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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