title: Assessing causality in the association between child adiposity and physical activity levels: a Mendelian randomization analysis.
abstract: BACKGROUND
  Cross-sectional studies have shown that objectively measured physical activity is associated with childhood adiposity, and a strong inverse dose-response association with body mass index (BMI) has been found. However, few studies have explored the extent to which this association reflects reverse causation. We aimed to determine whether childhood adiposity causally influences levels of physical activity using genetic variants reliably associated with adiposity to estimate causal effects.
  
  
  RESULTS
  The Avon Longitudinal Study of Parents and Children collected data on objectively assessed activity levels of 4,296 children at age 11 y with recorded BMI and genotypic data. We used 32 established genetic correlates of BMI combined in a weighted allelic score as an instrumental variable for adiposity to estimate the causal effect of adiposity on activity. In observational analysis, a 3.3 kg/m² (one standard deviation) higher BMI was associated with 22.3 (95% CI, 17.0, 27.6) movement counts/min less total physical activity (p = 1.6×10⁻¹⁶), 2.6 (2.1, 3.1) min/d less moderate-to-vigorous-intensity activity (p = 3.7×10⁻²⁹), and 3.5 (1.5, 5.5) min/d more sedentary time (p = 5.0×10⁻⁴). In Mendelian randomization analyses, the same difference in BMI was associated with 32.4 (0.9, 63.9) movement counts/min less total physical activity (p = 0.04) (∼5.3% of the mean counts/minute), 2.8 (0.1, 5.5) min/d less moderate-to-vigorous-intensity activity (p = 0.04), and 13.2 (1.3, 25.2) min/d more sedentary time (p = 0.03). There was no strong evidence for a difference between variable estimates from observational estimates. Similar results were obtained using fat mass index. Low power and poor instrumentation of activity limited causal analysis of the influence of physical activity on BMI.
  
  
  CONCLUSIONS
  Our results suggest that increased adiposity causes a reduction in physical activity in children and support research into the targeting of BMI in efforts to increase childhood activity levels. Importantly, this does not exclude lower physical activity also leading to increased adiposity, i.e., bidirectional causation.
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Richmond
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.affiliation: Department of Oral and Dental Science, University of Bristol, Bristol, United Kingdom.
authors.forename: Andy R
authors.initials: AR
authors.lastname: Ness
authors.affiliation: Molecular Epidemiology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Marcel
authors.initials: M
authors.lastname: den Hoed
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: George
authors.initials: G
authors.lastname: McMahon
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
mesh_terms: D015502:Absorptiometry, Photon; D050154:Adiposity; D015992:Body Mass Index; D002648:Child; D004739:England; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D057182:Mendelian Randomization Analysis; D009043:Motor Activity