Childhood Obesity and Age-Related Diseases: A Systematic Review and Meta-Analysis of Mendelian Randomization Evidence

BACKGROUND: Childhood obesity poses a global health threat, with emerging evidence suggesting distinct adipocyte senescence patterns compared to adult-onset obesity. We systematically explored whether childhood obesity may be causally associated with age-related diseases through a meta-analysis of Mendelian randomization (MR) evidence. METHODS: We screened six databases (MEDLINE, PubMed, EMBASE, Web of Science, Cochrane Library and CNKI) and identified 45 MR articles examining paediatric adiposity and major age-related diseases. For each disease, we performed a meta-analysis using results from published MR studies and conducted de novo analyses based on genetic data from UK Biobank (n = 453 169), FinnGen (n > 200 000) and other large consortiums. RESULTS: The meta-analysis examined 44 diseases across 9 systems, revealing suggestive associations between genetically determined childhood obesity and increased risk of 16 age-related diseases, including hypertension, atrial fibrillation, coronary artery disease, stroke and myocardial infarction; colorectal, endometrial and pancreatic cancers; nonalcoholic fatty liver disease, type 2 diabetes, diabetic nephropathy; multiple sclerosis and gout; Alzheimer's disease; depression and asthma. Three of these associations were marginal (p = 0.03-0.05). Paradoxical inverse associations emerged for breast cancer and ulcerative colitis. CONCLUSION: The findings from this meta-analysis underscore associations between childhood adiposity and multisystem age-related pathologies, underscoring the imperative for early obesity prevention.