Genetic insights into the causal relationship between physical activity and cognitive functioning

Boris Cheval; Liza Darrous; Karmel W Choi; Yann C Klimentidis; David A Raichlen; Gene E Alexander; Stéphane Cullati; Zoltán Kutalik; Matthieu P Boisgontier

doi:10.1038/s41598-023-32150-1

Genetic insights into the causal relationship between physical activity and cognitive functioning

Sci Rep. 2023 Mar 31;13(1):5310. doi: 10.1038/s41598-023-32150-1.

Authors

Boris Cheval^#^{1

2}, Liza Darrous^#^{3

4}, Karmel W Choi⁵, Yann C Klimentidis⁶, David A Raichlen^{7

8}, Gene E Alexander^{9

10

11

12}, Stéphane Cullati¹³, Zoltán Kutalik^{14

15}, Matthieu P Boisgontier^{16

17}

Affiliations

¹ Swiss Center for Affective Sciences, University of Geneva, Geneva, Switzerland. boris.cheval@unige.ch.
² Laboratory for the Study of Emotion Elicitation and Expression (E3Lab), Department of Psychology, University of Geneva, Geneva, Switzerland. boris.cheval@unige.ch.
³ University for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland. liza.darrous@unil.ch.
⁴ Swiss Institute of Bioinformatics, Lausanne, Switzerland. liza.darrous@unil.ch.
⁵ Department of Psychiatry, Massachusetts General Hospital, Massachusetts, Boston, MA, USA.
⁶ Department of Epidemiology and Biostatistics, University of Arizona, Tucson, AZ, USA.
⁷ Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA.
⁸ Department of Anthropology, University of Southern California, Los Angeles, CA, USA.
⁹ Department of Psychology, University of Arizona, Tucson, AZ, USA.
¹⁰ Department of Psychiatry, University of Arizona, Tucson, AZ, USA.
¹¹ Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, AZ, USA.
¹² Arizona Alzheimer's Consortium, Phoenix, AZ, USA.
¹³ Population Health Laboratory, Department of Community Health, University of Fribourg, Fribourg, Switzerland.
¹⁴ University for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland. zoltan.kutalik@unil.ch.
¹⁵ Swiss Institute of Bioinformatics, Lausanne, Switzerland. zoltan.kutalik@unil.ch.
¹⁶ School of Rehabilitation Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada. matthieu.boisgontier@uOttawa.ca.
¹⁷ Bruyère Research Institute, Ottawa, ON, Canada. matthieu.boisgontier@uOttawa.ca.

^# Contributed equally.

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, CI_95% = [0.17,0.47], P = 2.89e - 05) and vigorous physical activity (b = 0.22, CI_95% = [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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Causality
Cognition
Exercise*
Genome-Wide Association Study*
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide

Grants and funding

R01 HL136528/HL/NHLBI NIH HHS/United States