LAUSR

Abstract Funding Acknowledgements Type of funding sources: None. Background Observational studies have shown positive associations general and abdominal obesity, and atrial fibrillation (AF). However, little is known about these associations in individuals with elevated genetic susceptibility for this disease. Methods The UK Biobank cohort study includes more than 502 421 participants aged 40 to 70 years who were recruited from 22 assessment centers across the United Kingdom from 2006 to 2010. A total of 339 003 unrelated individuals of white British descent with available genotype and matching genetic data and reported sex were included in this study from the UK Biobank population-based sample. Individuals were included in the analyses of AF. Data were analyzed from April 2006 to March 2015. Body mass index (BMI) and waist circumference (WC) were employed for general (BMI: underweight, < 18.5 kg/m²; normal, 18.5 to <25.0 kg/m²; overweight, 25.0 to <30.0 kg/m²; obese, > 30.0 kg/m²) and abdominal obesity (WC: ≥ 94 cm for men and ≥ 80 cm for women). Then we further examined these associations in individuals with different genetic burden by stratifying individuals based on their genetic risk scores for atrial fibrillation. We compared disease risk among individuals in different tertiles of body mass index, and abdominal obesity using lowest tertiles as reference. Results Of 343 165 individuals, 185 745 (54.1%) were female, and the mean (SD) age was 57.19 ± 8.01 years. During follow-up, 18 974 of 343 165 (5.5%) developed AF with 8.2% in general obesity (vs. 4.7% control, p<0.001) and 6.6% in abdominal obesity (vs. 3.4% control, p<0.001). Compared to the normal, subjects in the overweight (HR 1.11, 95% CI 1.07–1.15, p<0.001) and obese (HR 1.55, 95% CI 1.20–2.01, p<0.001), and abdominal obesity (HR 1.35, 95% CI 1.31–1.40, p<0.001) had a significantly higher AF risk. Genetic risk and general and abdominal obesity were independent predictors of incident AF, and there were no interactions. Compared with normal in the low genetic risk group, general obesity and abdominal obesity was associated with a hazard ratio of up to 3.98 (95% CI, 3.73–4.24) and 3.44 (95% CI, 3.19–3.70) for AF in the high genetic risk group. Conclusions General and abdominal obesity demonstrated positive associations with incident AF in the general population, as well as in individuals with elevated genetic risk for these diseases.