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

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.

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.

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.

The findings from this meta-analysis underscore associations between childhood adiposity and multisystem age-related pathologies, underscoring the imperative for early obesity prevention.