TY - JOUR

T1 - Bidirectional Mendelian Randomization study of personality traits reveals a positive feedback loop between neuroticism and back pain

AU - Elgaeva, Elizaveta E

AU - Williams, Frances M K

AU - Zaytseva, Olga O

AU - Freidin, Maxim B

AU - Aulchenko, Yurii S

AU - Suri, Pradeep

AU - Tsepilov, Yakov A

N1 - Dr. Suri is employed by the VA Puget Sound Health Care System and is the Director of the Resource Core of 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. Dr. Tsepilov and Ms. Elgaeva were supported by the Russian Science Foundation (RSF) grant No 22-15-20037 and by the Government of the Novosibirsk region. The data analysis performed using computational resources of the “Bioinformatics” Joint Computational Center supported by the budget project No FWNR-2022-0020. Dr. Aulchenko is a cofounder and a co-owner of PolyOmica and PolyKnomics, private organizations providing services, research, and development in the field of computational and statistical genomics. The other authors declare no competing interests. Copyright © 2023. Published by Elsevier Inc.

PY - 2023/10

Y1 - 2023/10

N2 - We conducted a bidirectional Mendelian randomization study to examine the causal effects of six personality traits (anxiety, neuroticism, extraversion, openness to experience, agreeableness and conscientiousness) on back pain associated with health care use and the causal effect of back pain on the same risk factors. Genetic instruments for the personality traits and back pain were obtained from the largest published genome-wide association studies conducted in individuals of European ancestry. We used inverse weighted variance meta-analysis and Causal Analysis Using Summary Effect for primary analyses and sensitivity analyses to examine evidence for causal associations. We interpreted exposure-outcome associations as being consistent with a causal relationship if results of at least one primary analysis were statistically significant after accounting for multiple statistical testing (p-value < 0.0042), and the direction and magnitude of effect estimates were concordant between primary and sensitivity analyses. We found evidence for statistically significant bidirectional causal associations between neuroticism and back pain, with odds ratio 1.51 (95% confidence interval 1.37; 1.67) of back pain per neuroticism sum score standard deviation, p-value = 7.80e-16; and beta = 0.12, se = 0.04 of neuroticism sum score standard deviation per log odds of back pain, p-value = 2.48e-03. Other relationships did not meet our predefined criteria for causal association. PERSPECTIVE: The significant positive feedback loop between neuroticism and back pain highlights the importance of considering neuroticism in the management of patients with back pain.

AB - We conducted a bidirectional Mendelian randomization study to examine the causal effects of six personality traits (anxiety, neuroticism, extraversion, openness to experience, agreeableness and conscientiousness) on back pain associated with health care use and the causal effect of back pain on the same risk factors. Genetic instruments for the personality traits and back pain were obtained from the largest published genome-wide association studies conducted in individuals of European ancestry. We used inverse weighted variance meta-analysis and Causal Analysis Using Summary Effect for primary analyses and sensitivity analyses to examine evidence for causal associations. We interpreted exposure-outcome associations as being consistent with a causal relationship if results of at least one primary analysis were statistically significant after accounting for multiple statistical testing (p-value < 0.0042), and the direction and magnitude of effect estimates were concordant between primary and sensitivity analyses. We found evidence for statistically significant bidirectional causal associations between neuroticism and back pain, with odds ratio 1.51 (95% confidence interval 1.37; 1.67) of back pain per neuroticism sum score standard deviation, p-value = 7.80e-16; and beta = 0.12, se = 0.04 of neuroticism sum score standard deviation per log odds of back pain, p-value = 2.48e-03. Other relationships did not meet our predefined criteria for causal association. PERSPECTIVE: The significant positive feedback loop between neuroticism and back pain highlights the importance of considering neuroticism in the management of patients with back pain.

KW - Back Pain/epidemiology

KW - Feedback

KW - Genome-Wide Association Study

KW - Humans

KW - Mendelian Randomization Analysis

KW - Neuroticism

KW - Personality/genetics

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85169833639&origin=inward&txGid=7308aec2df1b6412a7c992356316420e

UR - https://www.mendeley.com/catalogue/a64770c7-ab7b-3e04-91bc-3e10da716fbe/

U2 - 10.1016/j.jpain.2023.05.012

DO - 10.1016/j.jpain.2023.05.012

M3 - Article

C2 - 37270142

VL - 24

SP - 1875

EP - 1885

JO - The journal of pain

JF - The journal of pain

SN - 1526-5900

IS - 10

ER -