TY - JOUR

T1 - Causal effects of psychosocial factors on chronic back pain: a bidirectional Mendelian randomisation study

AU - Williams, Frances M.K.

AU - Elgaeva, Elizaveta E.

AU - Freidin, Maxim B.

AU - Zaytseva, Olga O.

AU - Aulchenko, Yurii S.

AU - Tsepilov, Yakov A.

AU - Suri, Pradeep

N1 - Funding Information: Dr. Tsepilov was supported by the Russian Foundation for Basic Research (#20-04-00464). Dr. Aulchenko was supported by the Russian Ministry of Education and Science under the 5-100 Excellence Programme, 0259-2021-0009/АААА-А17-117092070032-4. Ms. Elgaeva was supported by the budget project #FWNR-2022-0020. Dr. Suri is an employee of the VA Puget Sound Health Care System and affiliated with the University of Washington Clinical Learning, Evidence and Research (CLEAR) Center, which was funded by NIAMS/NIH P30AR072572. The contents of this work do not represent the views of the US Department of Veterans Affairs, the National Institutes of Health, or the US Government. The study was conducted using the UK Biobank Resource under project #18219. We are grateful to the UK Biobank participants for making such research possible. We thank Dr. Alexandra Shadrina for the help with the development of the MR protocol. Publisher Copyright: © 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

PY - 2022/7

Y1 - 2022/7

N2 - Purpose: Risk factors for chronic back pain (CBP) may share underlying genetic factors, making them difficult to study using conventional methods. We conducted a bi-directional Mendelian randomisation (MR) study to examine the causal effects of risk factors (education, smoking, alcohol consumption, physical activity, sleep and depression) on CBP and the causal effect of CBP on the same risk factors. Methods: Genetic instruments for risk factors and CBP were obtained from the largest published genome-wide association studies (GWAS) of risk factor traits conducted in individuals of European ancestry. We used inverse weighted variance meta-analysis (IVW), Causal Analysis Using Summary Effect (CAUSE) and sensitivity analyses to examine evidence for causal associations. We interpreted exposure-outcome associations as being consistent with a causal relationship if results with IVW or CAUSE were statistically significant after accounting for multiple statistical testing (p < 0.003), and the direction and magnitude of effect estimates were concordant between IVW, CAUSE, and sensitivity analyses. Results: We found evidence for statistically significant causal associations between greater education (OR per 4.2 years of schooling = 0.54), ever smoking (OR = 1.27), greater alcohol consumption (OR = 1.29 per consumption category increase) and major depressive disorder (OR = 1.41) and risk of CBP. Conversely, we found evidence for significant causal associations between CBP and greater alcohol consumption (OR = 1.19) and between CBP and smoking (OR = 1.21). Other relationships did not meet our pre-defined criteria for causal association. Conclusion: Fewer years of schooling, smoking, greater alcohol consumption, and major depressive disorder increase the risk of CBP. CBP increases the risk of greater alcohol consumption and smoking.

AB - Purpose: Risk factors for chronic back pain (CBP) may share underlying genetic factors, making them difficult to study using conventional methods. We conducted a bi-directional Mendelian randomisation (MR) study to examine the causal effects of risk factors (education, smoking, alcohol consumption, physical activity, sleep and depression) on CBP and the causal effect of CBP on the same risk factors. Methods: Genetic instruments for risk factors and CBP were obtained from the largest published genome-wide association studies (GWAS) of risk factor traits conducted in individuals of European ancestry. We used inverse weighted variance meta-analysis (IVW), Causal Analysis Using Summary Effect (CAUSE) and sensitivity analyses to examine evidence for causal associations. We interpreted exposure-outcome associations as being consistent with a causal relationship if results with IVW or CAUSE were statistically significant after accounting for multiple statistical testing (p < 0.003), and the direction and magnitude of effect estimates were concordant between IVW, CAUSE, and sensitivity analyses. Results: We found evidence for statistically significant causal associations between greater education (OR per 4.2 years of schooling = 0.54), ever smoking (OR = 1.27), greater alcohol consumption (OR = 1.29 per consumption category increase) and major depressive disorder (OR = 1.41) and risk of CBP. Conversely, we found evidence for significant causal associations between CBP and greater alcohol consumption (OR = 1.19) and between CBP and smoking (OR = 1.21). Other relationships did not meet our pre-defined criteria for causal association. Conclusion: Fewer years of schooling, smoking, greater alcohol consumption, and major depressive disorder increase the risk of CBP. CBP increases the risk of greater alcohol consumption and smoking.

KW - Causation

KW - Epidemiology

KW - Low back pain

KW - Prognosis

KW - Risk factor

KW - Genome-Wide Association Study

KW - Humans

KW - Mendelian Randomization Analysis

KW - Depressive Disorder, Major

KW - Polymorphism, Single Nucleotide

KW - Back Pain/epidemiology

KW - Alcohol Drinking/adverse effects

UR - http://www.scopus.com/inward/record.url?scp=85131565297&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/59873c56-2e0a-3915-951b-5aadda692ed5/

U2 - 10.1007/s00586-022-07263-2

DO - 10.1007/s00586-022-07263-2

M3 - Article

C2 - 35662366

AN - SCOPUS:85131565297

VL - 31

SP - 1906

EP - 1915

JO - European Spine Journal

JF - European Spine Journal

SN - 0940-6719

IS - 7

ER -