The global burden and trends of thyroid cancer attributable to high BMI, and the causal impact of obesity: A study integrating GBD 1990–2021 and bidirectional Mendelian randomization

We assessed the global burden of thyroid cancer caused by high body mass index (BMI) from 1990 to 2021 and evaluated whether obesity is genetically supported as a causal risk factor using bidirectional Mendelian randomization (MR). First, we utilized the Global Burden of Disease (GBD) to estimate the deaths, disability-adjusted life years (DALYs), years lived with disability, and years of life lost (YLLs) attributable to high BMI for thyroid cancer, examining age- and sex-specific patterns from 1990 to 2021. Joinpoint regression analyzed temporal trends, and a decomposition analysis was performed to quantify the contributions of population growth, population aging, and epidemiological changes to the burden change. An autoregressive integrated moving average (ARIMA) model was used to forecast changes in the age-standardized death rate (ASDR). Second, we performed bidirectional MR to test whether genetic predisposition to obesity classes influences thyroid cancer risk and whether reverse causation is supported. The GBD analysis showed that high BMI contributed to 5255 global thyroid cancer deaths and 144,955 DALYs in 2021, with a persistently higher burden in females across all age groups. Death and DALY rates for both sexes increased significantly after age 60, with females exhibiting consistently higher rates across all age groups. While absolute numbers of deaths and DALYs increased substantially from 1990 to 2021, age-standardized rates remained relatively stable, and for all metrics women had higher values than men. Average annual percent changes (AAPCs) were found to be higher among males compared to females by joinpoint analysis. Population growth accounted mainly for increasing deaths and DALYs through decomposition analysis. The ARIMA analysis indicates that the level of ASDR among the male population will continue to rise in the future, and it will accelerate after 2025. In contrast, we did not detect a statistically significant causal effect of obesity on thyroid cancer in this MR analysis (Class 1: odds ratio [OR] = 0.82, P = .41; Class 2: OR = 0.96, P = .84; Class 3: OR = 0.86, P = .39). Key limitations include ancestry constraints of the available GWAS instruments and the use of summary-level data.