Abstract
BackgroundTo investigate the relationship between different classes of obesity and stroke, we conducted a stratified Mendelian randomization (MR) study.MethodsThe body mass index (BMI) data of 263,407 Europeans with three classes of obesity (obesity class I, 30 kg/m2 ≤ BMI < 35 kg/m2; obesity class II, 35 kg/m2 ≤ BMI < 40 kg/m2; obesity class III, 40 kg/m2 ≤ BMI) were extracted from the Genetic Investigation of ANthropometric Traits (GIANT) consortium. Summary-level data of stroke and its subtypes [ischemic stroke (IS) and intracerebral hemorrhage (ICH)] were obtained from the genome-wide association study (GWAS) meta-analysis, which was performed by the MEGASTROKE consortium. MR methods were used to identify the causal relationships.ResultsThe MR analysis revealed that both obesity class I [odds ratio (OR) = 1.08, 95% CI: 1.05–1.12, p = 1.0 × 10-5] and obesity class II (OR = 1.06, 95% CI: 1.03–1.09, p = 1 × 10-4) were significantly positively related to IS, while obesity class III was not (OR = 1.01, 95% CI: 0.96–1.06, p = 0.65). In contrast to IS, there was no class of obesity associated with ICH risk. Further examination of the relationship between obesity classification and IS subtypes revealed that certain degrees of obesity were related to large artery stroke (LAS) (OR = 1.14, 95% CI: 1.04–1.24, p = 2.8 × 10-3 for class I; OR = 1.08, 95% CI: 1.01–1.16, p = 0.002 for class II) and cardioembolic stroke (CES) (OR = 1.11, 95% CI: 1.02–1.20, p = 0.02 for class I; OR = 1.08, 95% CI: 1.02–1.15, p = 0.007 for class II).ConclusionsA higher risk of IS, but not ICH, could be linked to obesity classes I and II. A strong association between LAS and CES and obesity was observed among all IS subtypes in the obese population.
Highlights
Stroke, the second leading cause of death and disability worldwide, has put huge economic pressure and healthcare burden on patients worldwide [1, 2]
SNPs were selected as instrumental variables, and different classes of obesity were viewed as exposure factors, while stroke and its subtypes were regarded as the outcome diseases in this study
Data for this study were derived from the different classes of obesity genome-wide association study (GWAS) including 263,407 European populations and a 446,696 European stroke population
Summary
The second leading cause of death and disability worldwide, has put huge economic pressure and healthcare burden on patients worldwide [1, 2]. There is no doubt that the prevention and control of these risk factors will reduce the disease burden of stroke. Obesity caused by abnormal metabolism, as one of the major health threats to all populations, is viewed as a potential risk factor for stroke [4]. Conventional observational studies may be affected by many confounders when investigating the causal relationship between exposure factors (obesity) and outcome effects (stroke). Factors such as the distribution of fat and the condition of health are difficult to control using typical analytic methods. To investigate the relationship between different classes of obesity and stroke, we conducted a stratified Mendelian randomization (MR) study
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