Brain. 2021 Dec 15; doi: 10.1093/brain/awab334. Epub 2021 Dec 15.
Genetic basis to structural grey matter associations with chronic pain.
Brain : a journal of neurology
Scott F Farrell, Adrián I Campos, Pik-Fang Kho, Rutger M J de Zoete, Michele Sterling, Miguel E Rentería, Trung Thanh Ngo, Gabriel Cuéllar-Partida
Affiliations
Affiliations
- RECOVER Injury Research Centre, The University of Queensland, Herston, QLD, Australia.
- NHMRC Centre for Research Excellence in Road Traffic Injury Recovery, The University of Queensland, Herston, QLD, Australia.
- Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia.
- School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, St Lucia, QLD, Australia.
- Genetic Epidemiology Laboratory, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
- Molecular Cancer Epidemiology Laboratory, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
- School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
- School of Allied Health Science and Practice, The University of Adelaide, Adelaide, SA, Australia.
- Diamantina Institute, The University of Queensland and Translational Research Institute, Woolloongabba, QLD, Australia.
PMID: 34907416
DOI: 10.1093/brain/awab334
Abstract
Structural neuroimaging studies of individuals with chronic pain conditions have often observed decreased regional grey matter at a phenotypic level. However, it is not known if this association can be attributed to genetic factors. Here we employed a novel integrative data-driven and hypothesis-testing approach to determine whether there is a genetic basis to grey matter morphology differences in chronic pain. Using publicly available genome-wide association study summary statistics for regional chronic pain conditions (n = 196 963) and structural neuroimaging measures (n = 19 629-34 000), we applied bivariate linkage disequilibrium-score regression and latent causal variable analyses to determine the genetic correlations (rG) and genetic causal proportion (GCP) between these complex traits, respectively. Five a priori brain regions (i.e. prefrontal cortex, cingulate cortex, insula, thalamus and superior temporal gyrus) were selected based on systematic reviews of grey matter morphology studies in chronic pain. Across this evidence-based selection of five brain regions, 10 significant negative genetic correlations (out of 369) were found (false discovery rate < 5%), suggesting a shared genetic basis to both reduced regional grey matter morphology and the presence of chronic pain. Specifically, negative genetic correlations were observed between reduced insula grey matter morphology and chronic pain in the abdomen (mean insula cortical thickness), hips (left insula volume) and neck/shoulders (left and right insula volume). Similarly, a shared genetic basis was found for reduced posterior cingulate cortex volume in chronic pain of the hip (left and right posterior cingulate), neck/shoulder (left posterior cingulate) and chronic pain at any site (left posterior cingulate); and for reduced pars triangularis volume in chronic neck/shoulder (left pars triangularis) and widespread pain (right pars triangularis). Across these negative genetic correlations, a significant genetic causal proportion was only found between mean insula thickness and chronic abdominal pain [rG (standard error, SE) = -0.25 (0.08), P = 1.06 × 10-3; GCP (SE) = -0.69 (0.20), P = 4.96 × 10-4]. This finding suggests that the genes underlying reduced cortical thickness of the insula causally contribute to an increased risk of chronic abdominal pain. Altogether, these results provide independent corroborating evidence for observational reports of decreased grey matter of particular brain regions in chronic pain. Further, we show for the first time that this association is mediated (in part) by genetic factors. These novel findings warrant further investigation into the neurogenetic pathways that underlie the development and prolongation of chronic pain conditions.
© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: [email protected].
Keywords: chronic pain; genome-wide association study; grey matter; neuroimaging; statistical genetics
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