A 2-sample mendelian randomization study

Observational studies have reported that childhood obesity is positively associated with risks of type 2 diabetes (T2D) and coronary artery disease (CAD) in adults; however, whether this association is causal is still unclear. In the present study, we conducted the 2-sample Mendelian randomization (MR) studies to investigate whether childhood obesity is causally associated with T2D and CAD in adults. Seven single-nucleotide polymorphisms (SNPs) that significantly associated with childhood obesity were used as instrumental variables. The 2-sample MR analyses were performed with the summary-level data of large-sample genome-wide association studies to evaluate the causal effects of childhood obesity on adult T2D and CAD and the levels of cardiometabolic traits. The 2-sampleMR analyses suggested that each 1-unit increase in the log-odds of having childhood obesity was causally associated with an increased risk of adult T2D (odds ratio [OR]=1.16, 95% confidential interval [CI]=1.06–1.28; P=1.0 10) and CAD (OR= 1.07, 95% CI=1.02–1.12; P=4.0 10) based on the inverse-variance weighted method. The MR analyses also suggested that childhood obesitywas positively associatedwith the levels of adult bodymass index,waist circumference, hip circumference, waist and hip ratio, log-transformed fasting glucose, log-transformed homeostatic model assessment (HOMA) of insulin resistance (%), and triglycerides. The childhood obesity was negatively associated with the adult high-density lipoprotein cholesterol level; however, there was no evidence of a causal association between childhood obesity and the levels of fasting glucose, 2-hour glucose, HbA1c (%), logtransformed HOMA of ß-cell function (%), low-density lipoprotein cholesterol, or total cholesterol in adults. In conclusion, a genetic predisposition to childhood obesity was associated with an increased risk of adult T2D and CAD, providing causal relations between childhood obesity and the risks of T2D and CAD in adults; however, the results need to be validated with larger-scale intervention studies. Abbreviations: 95% CI = 95% confidential interval, BMI = body mass index, CAD = coronary artery disease, CARDIoGRAM = Coronary Artery Disease Genome-wide Replication and Meta-analysis, GWAS = genome-wide association study, HC = hip circumference, HDL-c = high-density lipoprotein cholesterol, HOMA-IR = homeostatic model assessment of insulin resistance, IV = instrumental variable, IVW= inverse variance weighted, LDL-c= low-density lipoprotein cholesterol, MR =Mendelian randomization, OR= odds ratio, RCT = randomized controlled trials, SD= standard deviation, SNP= single nucleotide polymorphism, T2D= type 2 diabetes, TC = total cholesterol, TG = triglycerides, WC = waist circumference, WHR = waist and hip ratio.