Abstract
Physical activity and cognitive functioning are strongly intertwined. However, the causal relationships underlying this association are still unclear. Physical activity can enhance brain functions, but healthy cognition may also promote engagement in physical activity. Here, we assessed the bidirectional relationships between physical activity and general cognitive functioning using Latent Heritable Confounder Mendelian Randomization (LHC-MR). Association data were drawn from two large-scale genome-wide association studies (UK Biobank and COGENT) on accelerometer-measured moderate, vigorous, and average physical activity (N = 91,084) and cognitive functioning (N = 257,841). After Bonferroni correction, we observed significant LHC-MR associations suggesting that increased fraction of both moderate (b = 0.32, CI95% = [0.17,0.47], P = 2.89e-05) and vigorous physical activity (b = 0.22, CI95% = [0.06,0.37], P = 0.007) lead to increased cognitive functioning. In contrast, we found no evidence of a causal effect of average physical activity on cognitive functioning, and no evidence of a reverse causal effect (cognitive functioning on any physical activity measures). These findings provide new evidence supporting a beneficial role of moderate and vigorous physical activity (MVPA) on cognitive functioning.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵b MPB and ZK jointly directed this work.
Competing interests The authors declare no conflict of interests.
Ethical approval This study was approved by the Ethics Committee of Geneva Canton, Switzerland (CCER-2019-00065).
Data sharing The datasets used for the analysis are openly available from the Neale Lab GWAS results at http://www.nealelab.is/uk-biobank and from the Social Science Genetic Association Consortium Downloads at https://www.thessgac.org/data. Only the new GWAS dataset created for the fractions of physical activity are available with permission from the UK Biobank https://www.ukbiobank.ac.uk/. The LHC-MR code is available at https://github.com/LizaDarrous/lhcMR.
Analyses have been updated using a the recently published Latent Heritable Confounder Mendelian Randomization analysis.