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Accelerometer-Derived and Genetically Inferred Physical Activity and Human Disease

By Shaan Khurshid, Lu-Chen Weng, Victor Nauffal, James Pirruccello, Rachael A Venn, Mostafa A Al-Alusi, Emelia J Benjamin, Patrick T Ellinor, Steven A. Lubitz

Posted 08 Aug 2021
medRxiv DOI: 10.1101/2021.08.05.21261586

Physical activity is favorable to health but the relations with human disease and causal effects are poorly quantified. Previous studies have largely relied on self-reported estimates1-3 which are subject to recall bias, confounding, and reverse causality. Using wrist-worn accelerometer measurements from the UK Biobank, we tested associations between moderate-to-vigorous physical activity (MVPA) - both total MVPA minutes and whether MVPA was above a guideline-based threshold of [≥]150 minutes/week4-6 - and incidence of over 1,200 diseases. In 96,466 adults who wore accelerometers for one week (mean age 62{+/-}8 years), MVPA was associated with 401 (33%) tested diseases at a false discovery rate of 1% during a median of 6.2 years follow-up. Greater MVPA was overwhelmingly associated with reduced disease risk (98% of associations) with hazard ratios (HRs) ranging from 0.10-0.95 per standard deviation (SD) and associations spanning all 18 disease categories tested. A similar pattern of associations was observed when assessing the guideline-based threshold of [≥]150 MVPA minutes/week. We examined a polygenic risk score for MVPA as an instrumental variable for activity within a separate UK Biobank sample (N=392,058, mean age 57{+/-}8 years). Greater genetically inferred MVPA was associated with reduced risk of 182 (14%) incident diseases (HR range 0.74-0.97 per 1 SD), and included strong associations conferring reduced risks of obstructive bronchitis, peripheral vascular disease, type 2 diabetes, and gastritis/duodenitis. Objective physical activity is broadly associated with lower disease incidence and many associations are consistent with a causal effect.

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