Reproducibility and associated regression dilution bias of accelerometer-derived physical activity and sleep in the UK Biobank

Background: Previous studies on the reproducibility of 7-day accelerometer measurements have been limited by small sample sizes and short follow-up periods. We aimed to assess the long-term reproducibility of accelerometer-derived physical activity and sleep, and to illustrate the impact of regression dilution bias on the association between daily step count and coronary heart disease (CHD) in UK Biobank (UKB). Methods: We analysed data from 3138 UKB participants in the main accelerometry sub-study with up to four repeat accelerometer measurements after 3-4 years. Nine physical activity and sleep phenotypes were extracted to capture different movement behaviours. Reproducibility was assessed using intraclass correlation coefficients (ICCs). The impact on disease associations was illustrated by considering daily step count and incident CHD using Cox regression (87 180 participants; 3899 CHD events), before and after correction for regression dilution. Results: Among the 3138 participants, 51% were women and the mean (SD) age was 63.1 (9.4) years. Reproducibility of phenotypes was moderate to good, with the ICC (95% CI) for overall activity at 0.75 (0.74-0.76), and individual phenotypes ranging from 0.58 (0.56-0.59) for sleep efficiency to 0.69 (0.68-0.70) for sedentary behaviour. In our example, the inverse association between daily step count and CHD showed a 20% lower risk of CHD per 4000 usual steps after correcting for regression dilution, compared to 13% before correction. Conclusions: Accelerometer measurements are moderately reproducible and comparable to measures like blood pressure. Correcting for regression dilution bias is crucial to quantify associations of usual physical activity and sleep with disease risk.