Causal relationships between obesity and the leading causes of death in women and men

Autoři: Jenny C. Censin aff001;  Sanne A. E. Peters aff003;  Jonas Bovijn aff001;  Teresa Ferreira aff001;  Sara L. Pulit aff001;  Reedik Mägi aff007;  Anubha Mahajan aff002;  Michael V. Holmes aff009;  Cecilia M. Lindgren aff001
Působiště autorů: Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom aff001;  Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom aff002;  The George Institute for Global Health, University of Oxford, Oxford, United Kingdom aff003;  Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands aff004;  Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands aff005;  Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America aff006;  Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia aff007;  Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom aff008;  NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom aff009;  Medical Research Council Population Health Research Unit at the University of Oxford, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom aff010;  Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, Big Data Institute Building, Roosevelt Drive, University of Oxford, Oxford, United Kingdom aff011
Vyšlo v časopise: Causal relationships between obesity and the leading causes of death in women and men. PLoS Genet 15(10): e32767. doi:10.1371/journal.pgen.1008405
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008405


Obesity traits are causally implicated with risk of cardiometabolic diseases. It remains unclear whether there are similar causal effects of obesity traits on other non-communicable diseases. Also, it is largely unexplored whether there are any sex-specific differences in the causal effects of obesity traits on cardiometabolic diseases and other leading causes of death. We constructed sex-specific genetic risk scores (GRS) for three obesity traits; body mass index (BMI), waist-hip ratio (WHR), and WHR adjusted for BMI, including 565, 324, and 337 genetic variants, respectively. These GRSs were then used as instrumental variables to assess associations between the obesity traits and leading causes of mortality in the UK Biobank using Mendelian randomization. We also investigated associations with potential mediators, including smoking, glycemic and blood pressure traits. Sex-differences were subsequently assessed by Cochran’s Q-test (Phet). A Mendelian randomization analysis of 228,466 women and 195,041 men showed that obesity causes coronary artery disease, stroke (particularly ischemic), chronic obstructive pulmonary disease, lung cancer, type 2 and 1 diabetes mellitus, non-alcoholic fatty liver disease, chronic liver disease, and acute and chronic renal failure. Higher BMI led to higher risk of type 2 diabetes in women than in men (Phet = 1.4×10−5). Waist-hip-ratio led to a higher risk of chronic obstructive pulmonary disease (Phet = 3.7×10−6) and higher risk of chronic renal failure (Phet = 1.0×10−4) in men than women. Obesity traits have an etiological role in the majority of the leading global causes of death. Sex differences exist in the effects of obesity traits on risk of type 2 diabetes, chronic obstructive pulmonary disease, and renal failure, which may have downstream implications for public health.

Klíčová slova:

Blood pressure – Body Mass Index – Cancer risk factors – Genome-wide association studies – Chronic obstructive pulmonary disease – Ischemic stroke – Obesity


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Genetika Reprodukční medicína

Článek vyšel v časopise

PLOS Genetics

2019 Číslo 10

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