Abstract Body (Do not enter title and authors here): Introduction/Background
Atrial fibrillation (AF) is a prevalent arrhythmia associated with significant morbidity. While obesity, defined by body mass index (BMI), is a known risk factor, the roles of central adiposity (waist-to-hip ratio, WHR) and comorbidities remain underexplored. Understanding these interdependent mechanisms is critical for targeted AF prevention.

Research Question/Hypothesis
We hypothesized that WHR and cardiometabolic comorbidities—hypertension, diabetes, and sleep apnea—mediate the association between BMI and AF, explaining the attenuation often termed the “Obesity Paradox.”

Methods
We conducted a cross-sectional analysis using the All of Us research cohort within the Workbench environment, using Python. The primary outcome was AF status. Age at earliest AF diagnosis and corresponding BMI were recorded; for controls, the most recent values were used. Covariates included demographics, comorbidity burden (Charlson Comorbidity Index, CCI), and AF-related conditions. Chi-square tests assessed AF prevalence across obesity phenotypes. Three logistic regression models evaluated total and adjusted odds ratios (ORs) for AF and mediation through comorbidities.

Results/Data
The cohort included 390,245 individuals (4.58% with AF). AF patients were older (63.88 vs. 50.66 years, p<0.001), more often male (54.8% vs. 37.8%, p<0.001), and had higher CCI (2.39 vs. 0.59, p<0.001). AF prevalence varied by BMI/WHR phenotype (p<0.001), highest in Obese BMI/High WHR (5.54%) vs. Normal BMI/Normal WHR (2.04%).

Total effect model (minimally adjusted for covariates): Obese Class IV (OR=2.58) and very high WHR (OR=1.52) increased AF odds (p<0.001).
Mediation model: Obese Class IV increased odds of hypertension (OR=5.32), sleep apnea (OR=14.73), and diabetes (OR=6.17) (all p<0.001).
Adjusted model: Age, male sex, CCI (OR=1.29), hypertension (OR=4.88), sleep apnea (OR=1.98), and thyroid disorder (OR=1.44) were independently linked to AF (p<0.001). Obesity’s direct effect was attenuated. Obese Class IV with sleep apnea had compounded AF risk (OR ≈ 3.35, p<0.001).

Conclusion
In conclusion, our large-scale analysis definitively shows that while obesity significantly elevates AF risk, its direct impact is profoundly mediated by comorbidities, thereby explaining the long-observed obesity paradox. Age, sex, and comorbidity burden remain strong independent predictors. Managing conditions like sleep apnea in obese patients may reduce AF risk.