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Background: Recent updates to physical activity guidelines highlight the importance of reducing sedentary time. However, at present, only general recommendations are possible (ie, “Sit less, move more”). There remains a need to investigate the strength, temporality, specificity, and dose–response nature of sedentary behavior associations with chronic disease, along with potential underlying mechanisms. Methods: Stemming from a recent research workshop organized by the Sedentary Behavior Council themed “Sedentary behaviour mechanisms—biological and behavioural pathways linking sitting to adverse health outcomes,” this paper (1) discusses existing challenges and scientific discussions within this advancing area of science, (2) highlights and discusses emerging areas of interest, and (3) points to potential future directions. Results: A brief knowledge update is provided, reflecting upon current and evolving thinking/discussions, and the rapid accumulation of new evidence linking sedentary behavior to chronic disease. Research “action points” are made at the end of each section—spanning from measurement systems and analytic methods, genetic epidemiology, causal mediation, and experimental studies to biological and behavioral determinants and mechanisms. Conclusion: A better understanding of whether and how sedentary behavior is causally related to chronic disease will allow for more meaningful conclusions in the future and assist in refining clinical and public health policies/recommendations.

Wijndaele and Lynch are co-senior authors. Dempsey, Wareham, and Wijndaele are with MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom. Dempsey, Dunstan, and Lynch are with Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. Matthews is with Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Dashti and Lynch are with the Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. Doherty is with Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom; and NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom. Bergouignan is with IPHC UMR 7178, CNRS, Université de Strasbourg, Strasbourg, France; and the Division of Endocrinology, Metabolism and Diabetes, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA. van Roekel is with the Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands. Dunstan is also with Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, VIC, Australia. Yates is with Diabetes Research Centre, University of Leicester, Leicester, United Kingdom; and the NIHR Leicester Biomedical Research Centre, Leicester, United Kingdom. Lynch is also with Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.

Dempsey (paddy.dempsey@baker.edu.au) is corresponding author.
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