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

Autor: Michael V. Holmes, Sara L. Pulit, Cecilia M. Lindgren, Peters Sae., Anubha Mahajan, Jenny C Censin, Teresa Ferreira, Jonas Bovijn, Reedik Mägi
Rok vydání: 2019
Předmět:
Male
Cancer Research
Pulmonology
Physiology
Epidemiology
Blood Pressure
Type 2 diabetes
Disease
Coronary Artery Disease
QH426-470
Vascular Medicine
Body Mass Index
Pulmonary Disease
Chronic Obstructive
0302 clinical medicine
Waist–hip ratio
Endocrinology
Risk Factors
Cause of Death
Neoplasms
Medicine and Health Sciences
Genetics (clinical)
Cause of death
Adiposity
2. Zero hunger
0303 health sciences
Cancer Risk Factors
Genomics
Middle Aged
3. Good health
Stroke
Physiological Parameters
Neurology
Oncology
Female
Research Article
medicine.medical_specialty
Endocrine Disorders
Chronic Obstructive Pulmonary Disease
Cerebrovascular Diseases
Biology
Polymorphism
Single Nucleotide
03 medical and health sciences
Internal medicine
Diabetes mellitus
Mendelian randomization
medicine
Diabetes Mellitus
Genome-Wide Association Studies
Genetics
Humans
Obesity
Molecular Biology
Ecology
Evolution
Behavior and Systematics
030304 developmental biology
Aged
Ischemic Stroke
Waist-Hip Ratio
Body Weight
Biology and Life Sciences
Computational Biology
Human Genetics
Mendelian Randomization Analysis
medicine.disease
Genome Analysis
Diabetes Mellitus
Type 2
Metabolic Disorders
Medical Risk Factors
Body mass index
030217 neurology & neurosurgery
Genome-Wide Association Study
Zdroj: PLoS Genetics
PLoS Genetics, Vol 15, Iss 10, p e1008405 (2019)
ISSN: 1553-7404
Popis: 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.
Author summary Obesity is increasing globally and has been linked to major causes of death, such as diabetes and heart disease. Still, the causal effects of obesity on other leading causes of death is relatively unexplored. It is also unclear if any such effects differ between men and women. Mendelian randomization is a method that explores causal relationships between traits using genetic data. Using Mendelian randomization, we investigated the effects of obesity traits on leading causes of death and assessed if any such effects differ between men and women. We found that obesity increases the risks of heart disease, stroke, chronic obstructive pulmonary disease, lung cancer, diabetes, kidney disease, non-alcoholic fatty liver disease and chronic liver disease. Higher body mass index led to a higher risk of type 2 diabetes in women than in men, whereas a higher waist-hip ratio increased risks of chronic obstructive pulmonary disease and chronic kidney disease more in men than in women. In summary, obesity traits are causally involved in the majority of the leading causes of death, and some obesity traits affect disease risk differently in men and women. This has potential implications for public health strategies and indicates that sex-specific preventative measures may be needed.
Databáze: OpenAIRE
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