Journal Article

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

Bovijn, Jonas, Holmes, Michael V., Censin, Jenny C., Pulit, Sara L., Mägi, Reedik, Lindgren, Cecilia M., Ferreira, Teresa, Peters, Sanne A. E., Mahajan, Anubha

2019

نظرة عامة

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.

• الناشر: Public Library of Science,Public Library of Science (PLoS)
• موضوع: Adiposity - genetics / Aged / Analysis / Big Data / Biology and Life Sciences / Blood pressure / Blood Pressure - genetics / Body Mass Index / Breast cancer / Cardiovascular disease / Cause of Death / Chronic kidney failure / Chronic obstructive pulmonary disease / Colorectal cancer / Communicable diseases / Coronary artery / Coronary Artery Disease - complications / Coronary Artery Disease - genetics / Coronary Artery Disease - mortality / Coronary Artery Disease - pathology / Coronary heart disease / Death / Diabetes / Diabetes mellitus / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - genetics / Diabetes Mellitus, Type 2 - mortality / Diabetes Mellitus, Type 2 - pathology / Epidemiology / Fatty liver / Female / Gender differences / Genetic diversity / Genetics / Genome-Wide Association Study / Genomes / Health risk assessment / Heart diseases / Hip / Humans / Ischemia / Kidney diseases / Kidney failure / Liver / Liver diseases / Lung cancer / Lung diseases / Male / Medicine / Medicine and Health Sciences / Mendelian Randomization Analysis / Methods / Middle Aged / Mortality / Neoplasms / Obesity / Obesity - complications / Obesity - genetics / Obesity - mortality / Obesity - pathology / Obstructive lung disease / Polymorphism, Single Nucleotide / Population genetics / Public health / Public health movements / Pulmonary Disease, Chronic Obstructive - complications / Pulmonary Disease, Chronic Obstructive - genetics / Pulmonary Disease, Chronic Obstructive - mortality / Pulmonary Disease, Chronic Obstructive - pathology / Questions and answers / Renal failure / Respiratory tract diseases / Risk Factors / Sex differences / Software / Stroke / Studies / Type 2 diabetes / United Kingdom / Waist-Hip Ratio / Womens health