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Am J Hum Genet. 2014 Feb 6;94(2):198-208. doi: 10.1016/j.ajhg.2013.12.014. Epub 2014 Jan 23.

Causal effects of body mass index on cardiometabolic traits and events: a Mendelian randomization analysis.

Author information

1
Division of Transplantation, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA; Genetic Epidemiology Group, Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK. Electronic address: michael.holmes@uphs.upenn.edu.
2
Department of Genetics, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, NC 27514, USA.
3
Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
4
Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
5
Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
6
Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
7
Jackson Heart Study Coordinating Center, Jackson State University, 350 West Woodrow Wilson Avenue, Suite 701, Jackson, MS 39213, USA.
8
Complex Genetics Section, Department of Medical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
9
Division of Atherosclerosis & Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
10
Genetic Epidemiology Group, Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK.
11
Departments of Medicine and Pathology, University of Vermont, 208 South Park Drive, Colchester, VT 05446 USA.
12
The Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
13
Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA.
14
The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
15
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
16
Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, WA 98101, USA.
17
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55414, USA.
18
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
19
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
20
Genetic Epidemiology Group, Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK; Faculty of Epidemiology and Public Health, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK.
21
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands; Brigham and Women's Hospital, 77 Avenue Louis Pasteur, New Research Building, Room 168, Boston, MA 02115, USA.
22
Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
23
Department of Genomics, Mount Sinai School of Medicine, New York, NY 10029, USA.
24
Division of Heart and Lungs, Department of Cardiology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands; Durrer Center for Cardiogenetic Research, ICIN - Netherlands Heart Institute, Catharijnesingel 52, Postbus 19258, 3501 DG Utrecht, the Netherlands; Faculty of Population Health Sciences, Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK.
25
Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
26
Division of Transplantation, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA; Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA. Electronic address: bkeating@mail.med.upenn.edu.

Erratum in

  • Am J Hum Genet. 2014 Feb 6;94(2):312.

Abstract

Elevated body mass index (BMI) associates with cardiometabolic traits on observational analysis, yet the underlying causal relationships remain unclear. We conducted Mendelian randomization analyses by using a genetic score (GS) comprising 14 BMI-associated SNPs from a recent discovery analysis to investigate the causal role of BMI in cardiometabolic traits and events. We used eight population-based cohorts, including 34,538 European-descent individuals (4,407 type 2 diabetes (T2D), 6,073 coronary heart disease (CHD), and 3,813 stroke cases). A 1 kg/m(2) genetically elevated BMI increased fasting glucose (0.18 mmol/l; 95% confidence interval (CI) = 0.12-0.24), fasting insulin (8.5%; 95% CI = 5.9-11.1), interleukin-6 (7.0%; 95% CI = 4.0-10.1), and systolic blood pressure (0.70 mmHg; 95% CI = 0.24-1.16) and reduced high-density lipoprotein cholesterol (-0.02 mmol/l; 95% CI = -0.03 to -0.01) and low-density lipoprotein cholesterol (LDL-C; -0.04 mmol/l; 95% CI = -0.07 to -0.01). Observational and causal estimates were directionally concordant, except for LDL-C. A 1 kg/m(2) genetically elevated BMI increased the odds of T2D (odds ratio [OR] = 1.27; 95% CI = 1.18-1.36) but did not alter risk of CHD (OR 1.01; 95% CI = 0.94-1.08) or stroke (OR = 1.03; 95% CI = 0.95-1.12). A meta-analysis incorporating published studies reporting 27,465 CHD events in 219,423 individuals yielded a pooled OR of 1.04 (95% CI = 0.97-1.12) per 1 kg/m(2) increase in BMI. In conclusion, we identified causal effects of BMI on several cardiometabolic traits; however, whether BMI causally impacts CHD risk requires further evidence.

PMID:
24462370
PMCID:
PMC3928659
DOI:
10.1016/j.ajhg.2013.12.014
[Indexed for MEDLINE]
Free PMC Article

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