2019-01-23
Assessment of Bidirectional Relationships Between Physical Activity and Depression Among Adults A 2-Sample Mendelian Randomization Study
Publication
Publication
JAMA Psychiatry , Volume 76 - Issue 4 p. 399- 408
IMPORTANCE Increasing evidence shows that physical activity is associated with reduced risk
for depression, pointing to a potential modifiable target for prevention. However, the
causality and direction of this association are not clear; physical activity may protect against
depression, and/or depression may result in decreased physical activity.
OBJECTIVE To examine bidirectional relationships between physical activity and depression
using a genetically informed method for assessing potential causal inference.
DESIGN, SETTING, AND PARTICIPANTS This 2-sample mendelian randomization (MR) used
independent top genetic variants associated with 2 physical activity phenotypes—
self-reported (n = 377 234) and objective accelerometer-based (n = 91 084)—and with major
depressive disorder (MDD) (n = 143 265) as genetic instruments from the largest available,
nonoverlapping genome-wide association studies (GWAS). GWAS were previously conducted
in diverse observational cohorts, including the UK Biobank (for physical activity) and
participating studies in the Psychiatric Genomics Consortium (for MDD) among adults of
European ancestry. Mendelian randomization estimates from each genetic instrument
were combined using inverse variance weighted meta-analysis, with alternate methods
(eg, weighted median, MR Egger, MR–Pleiotropy Residual Sum and Outlier [PRESSO]) and
multiple sensitivity analyses to assess horizontal pleiotropy and remove outliers. Data were
analyzed from May 10 through July 31, 2018.
MAIN OUTCOMES AND MEASURES MDD and physical activity.
RESULTS GWAS summary data were available for a combined sample size of 611 583 adult
participants. Mendelian randomization evidence suggested a protective relationship between
accelerometer-based activity and MDD (odds ratio [OR], 0.74 for MDD per 1-SD increase in
mean acceleration; 95% CI, 0.59-0.92; P = .006). In contrast, there was no statistically
significant relationship between MDD and accelerometer-based activity (β = −0.08 in mean
acceleration per MDD vs control status; 95% CI, −0.47 to 0.32; P = .70). Furthermore, there
was no significant relationship between self-reported activity and MDD (OR, 1.28 for MDD
per 1-SD increase in metabolic-equivalent minutes of reported moderate-to-vigorous activity;
95% CI, 0.57-3.37; P = .48), or between MDD and self-reported activity (β = 0.02 per MDD
in standardized metabolic-equivalent minutes of reported moderate-to-vigorous activity
per MDD vs control status; 95% CI, −0.008 to 0.05; P = .15).
CONCLUSIONS AND RELEVANCE Using genetic instruments identified from large-scale GWAS,
robust evidence supports a protective relationship between objectively assessed—but not
self-reported—physical activity and the risk for MDD. Findings point to the importance of
objective measurement of physical activity in epidemiologic studies of mental health and
support the hypothesis that enhancing physical activity may be an effective prevention
strategy for depression.
Additional Metadata | |
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doi.org/10.1001/jamapsychiatry.2018.4175, hdl.handle.net/1765/116928 | |
JAMA Psychiatry | |
Organisation | Department of Epidemiology |
Choi, K., C.Y. Chen (Chia-Yen), M.B. Stein (Murray), Y.C. Klimentidis (Yann), M.J. Wang (Min-Jung), K.C. Koenen (Karestan), & J.W. Smoller (Jordan). (2019). Assessment of Bidirectional Relationships Between Physical Activity and Depression Among Adults A 2-Sample Mendelian Randomization Study. JAMA Psychiatry, 76(4), 399–408. doi:10.1001/jamapsychiatry.2018.4175 |