Genetically Downregulated Interleukin-6 Signaling Is Associated with a Favorable Cardiometabolic Profile: A Phenome-Wide Association Study

TY - JOUR

T1 - Genetically Downregulated Interleukin-6 Signaling Is Associated with a Favorable Cardiometabolic Profile

T2 - A Phenome-Wide Association Study

AU - Regeneron Genetics Center

AU - Georgakis, Marios K.

AU - Malik, Rainer

AU - Li, Xue

AU - Gill, Dipender

AU - Levin, Michael G.

AU - Vy, Ha My T.

AU - Judy, Renae

AU - Ritchie, Marylyn

AU - Verma, Shefali S.

AU - Nadkarni, Girish N.

AU - Damrauer, Scott M.

AU - Theodoratou, Evropi

AU - Dichgans, Martin

N1 - Funding Information: This research has been conducted using the UK Biobank Resource (UK Biobank application 2532, “UK Biobank Stroke Study: Developing an In-depth Understanding of the Determinants of Stroke and its Subtypes”). The authors thank the following studies and consortia for making summary data from genome-wide association studies publicly available: the INTERVAL study (A Randomised Trial to Determine Whether the Interval Between Blood Donations in England Can be Safely and Acceptably Decreased), YFS (Cardiovascular Risk in Young Finns Study) and the FINRISK Study, the MAGIC (Meta-Analyses of Glucose and Insulin-related Traits) consortium, the genome-wide association study for nuclear magnetic resonance–measured metabolites by Kettunen et al, and the GIANT (Genetic Investigation of Anthropometric Traits) consortium. The authors thank the personnel and the participants of the Penn Medicine Biobank and BioMe Biobank. The Regeneron Genetics Center Banner contributions are as follows (all authors/contributors are listed in alphabetic order): RGC Management and Leadership Team: Goncalo Abecasis, PhD, Aris Baras, MD, Michael Cantor, MD, Giovanni Coppola, MD, Aris Economides, PhD, John D. Overton, PhD, Jeffrey G. Reid, PhD, and Alan R. Shuldiner, MD. Sequencing and Laboratory Operations: Christina Beechert, Caitlin Forsythe, MS, Erin D. Fuller, Zhenhua Gu, MS, Michael Lattari, Alexander Lopez, MS, John D. Overton, PhD, Thomas D. Schleicher, MS, Maria Sotiropoulos Padilla, MS, Karina Toledo, Louis Widom, Sarah E. Wolf, MS, Manasi Pradhan, MS, Kia Manoochehri, and Ricardo H. Ulloa. Genome Informatics: Xiaodong Bai, PhD, Suganthi Balasubramanian, PhD, Leland Barnard, PhD, Andrew Blumenfeld, Yating Chai, PhD, Gisu Eom, Lukas Habegger, PhD, Young Hahn, Alicia Hawes, BS, Shareef Khalid, Jeffrey G. Reid, PhD, Evan K. Maxwell, PhD, John Penn, MS, Jeffrey C. Staples, PhD, and Ashish Yadav, MS. Planning, Strategy, and Operations: Paloma M. Guzzardo, PhD, Marcus B. Jones, PhD, and Lyndon J. Mitnaul, PhD. Dr Georgakis has received funding from the Onassis Foundation. Dr Gill is supported by the British Heart Foundation Center of Research Excellence (RE/18/4/34215) at Imperial College London. Dr Damrauer is supported by the US Department of Veterans Affairs (IK2-CX001780); this work does not express the views of the US Department of Veterans Affairs or the US Government. Dr Theodoratou is funded by Cancer Research UK (C31250/A22804). This project has received funding from the European Union’s Horizon 2020 research and innovation program (666881); “Small vessel diseases in a mechanistic perspective: Targets for Intervention” ([SVDs@target] 667375 to MD); CoSTREAM ([Common mechanisms and pathways in stroke and Alzheimer’s disease] to MD); the German Research Foundation as part of the Munich Cluster for Systems Neurology (EXC2145 SyNergy–ID 390857198) and the Collaborative Research Centers ([CRC 1123] B3 to MD); the Corona Foundation (to MD); the Fondation Leducq ([Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain] to MD); the e:Med program ([e:AtheroSysMed] to MD); and the Seventh Framework Pro-gramme (2007 to 2103) European Union project “Exploitation of Genomic Variants Affecting Coronary Artery Disease and Stroke Risk for Therapeutic Intervention” (CVgenes@target Health-F2-2013-601456 to MD). Funding Information: Dr Georgakis has received funding from the Onassis Foundation. Dr Gill is supported by the British Heart Foundation Center of Research Excellence (RE/18/4/34215) at Imperial College London. Dr Damrauer is supported by the US Department of Veterans Affairs (IK2-CX001780); this work does not express the views of the US Department of Veterans Affairs or the US Government. Dr Theodoratou is funded by Cancer Research UK (C31250/A22804). This project has received funding from the European Union’s Horizon 2020 research and innovation program (666881); “Small vessel diseases in a mechanistic perspective: Targets for Intervention” ([SVDs@target] 667375 to MD); CoSTREAM ([Common mechanisms and pathways in stroke and Alzheimer’s disease] to MD); the German Research Foundation as part of the Munich Cluster for Systems Neurology (EXC2145 SyNergy–ID 390857198) and the Collaborative Research Centers ([CRC 1123] B3 to MD); the Corona Foundation (to MD); the Fondation Leducq ([Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain] to MD); the e:Med program ([e:AtheroSysMed] to MD); and the Seventh Framework Programme (2007 to 2103) European Union project “Exploitation of Genomic Variants Affecting Coronary Artery Disease and Stroke Risk for Therapeutic Intervention” (CVgenes@target Health-F2-2013-601456 to MD).

PY - 2021/3/16

Y1 - 2021/3/16

KW - biomarkers

KW - cardiovascular diseases

KW - cholesterol, HDL

KW - diabetes mellitus, type 2

KW - genetics

KW - interleukin-6

UR - https://www.scopus.com/pages/publications/85102915115

U2 - 10.1161/CIRCULATIONAHA.120.052604

DO - 10.1161/CIRCULATIONAHA.120.052604

M3 - Letter

C2 - 33720771

AN - SCOPUS:85102915115

SN - 0009-7322

VL - 143

SP - 1177

EP - 1180

JO - Circulation

JF - Circulation

IS - 11

ER -