Childhood Obesity Leads to Adult Type 2 Diabetes and Coronary Artery Diseases: A Two-Sample Mendelian Randomization Study

Background: Observational studies have reported that childhood obesity is positively associated with risks of type 2 diabetes (T2D) and coronary artery disease (CAD) in adulthood; however, whether this association is causal is unknown. Methods: Two-sample MR analyses with 7 single nucleotide polymorphisms (SNPs) as instrumental variables for childhood obesity 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. Findings: The MR 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 × 10-3) and CAD (OR = 1.07, 95% CI = 1.02-1.12; P = 4.0 × 10-3) based on the inverse-variance weighted method. In further, the MR analyses also suggested that childhood obesity was positively associated with adult body mass index, waist circumference, hip circumference, waist and hip ratio, log-transformed fasting insulin, log-transformed HOMA of insulin resistance, and triglycerides, and it was negatively associated with adult high-density lipoprotein level. The MR analyses found no evidence of a causal association between childhood obesity and fasting glucose, 2-hour glucose, HbA1c, log-transformed HOMA of s-cell function, low-density lipoprotein, or total cholesterol in adults. Interpretation: 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 outcomes; however, the results need to be validated with larger-scale intervention studies. Funding Statement: The work was financially supported by the by grants from the Science and Technology Commission of Shanghai Municipality (16411966800), the Shanghai Municipal Commission of Health and Family Planning (20164Y0250), Science and Technology Commission of Jiading Distinct (JDKW-2017-W09), and the grants by Ruijin Hospital North for Young Talents (2017RCPY-A01 and 2017RCPY-C01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Declaration of Interests: The authors declared that they have no competing financial interests.