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The genetic architecture of pain intensity in a sample of 598,339 U.S. veterans.

ABSTRACT: Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids played a central role in precipitating the opioid crisis. Despite an estimated heritability of 25-50%, the genetic architecture of chronic pain is not well characterized, in part because studies have largely been limited to samples of European ancestry. To help address this knowledge gap, we conducted a cross-ancestry meta-analysis of pain intensity in 598,339 participants in the Million Veteran Program, which identified 125 independent genetic loci, 82 of which are novel. Pain intensity was genetically correlated with other pain phenotypes, level of substance use and substance use disorders, other psychiatric traits, education level, and cognitive traits. Integration of the GWAS findings with functional genomics data shows enrichment for putatively causal genes (n = 142) and proteins (n = 14) expressed in brain tissues, specifically in GABAergic neurons. Drug repurposing analysis identified anticonvulsants, beta-blockers, and calcium-channel blockers, among other drug groups, as having potential analgesic effects. Our results provide insights into key molecular contributors to the experience of pain and highlight attractive drug targets.

SUBMITTER: Toikumo S

PROVIDER: S-EPMC10055465 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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The genetic architecture of pain intensity in a sample of 598,339 U.S. veterans.

Toikumo Sylvanus S Vickers-Smith Rachel R Jinwala Zeal Z Xu Heng H Saini Divya D Hartwell Emily E Venegas Mirko P MP Sullivan Kyle A KA Xu Ke K Jacobson Daniel A DA Gelernter Joel J Rentsch Christopher T CT Stahl Eli E Cheatle Martin M Zhou Hang H Waxman Stephen G SG Justice Amy C AC Kember Rachel L RL Kranzler Henry R HR

medRxiv : the preprint server for health sciences 20230313

Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids played a central role in precipitating the opioid crisis. Despite an estimated heritability of 25-50%, the genetic architecture of chronic pain is not well characterized, in part because studies have largely been limited to samples of European ancest ...[more]

PMID: 36993749

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Project description:BackgroundOver 25% of veterans seeking care at U.S. Veterans Health Administration facilities have chronic low back pain (LBP), with high rates of mental health comorbidities. The primary objective of this study was to assess the feasibility of participant recruitment, retention, and electronic data collection to prepare for the subsequent randomized trial of multimodal chiropractic care for pain management of veterans with chronic low back pain. The secondary objectives were to estimate effect sizes and variability of the primary outcome and choose secondary outcomes for the full-scale trial.MethodsThis single-arm pilot trial enrolled 40 veterans with chronic LBP at one Veterans Health Administration facility for a 10-week course of pragmatic multimodal chiropractic care. Recruitment was by (1) provider referral, (2) invitational letter from the electronic health record pre-screening, and (3) standard direct recruitment. We administered patient-reported outcome assessments through an email link to REDCap, an electronic data capture platform, at baseline and 5 additional timepoints. Retention was tracked through adherence to the treatment plan and completion rates of outcome assessments. Descriptive statistics were calculated for baseline characteristics and outcome variables.ResultsWe screened 91 veterans over 6 months to enroll our goal of 40 participants. Seventy percent were recruited through provider referrals. Mean age (range) was 53 (22-79) years and 23% were female; 95% had mental health comorbidities. The mean number of chiropractic visits was 4.5 (1-7). Participants adhered to their treatment plan, with exception of 3 who attended only their first visit. All participants completed assessments at the in-person baseline visit and 80% at the week 10 final endpoint. We had no issues administering assessments via REDCap. We observed clinically important improvements on the Roland-Morris Disability Questionnaire [mean change (SD): 3.6 (6.1)] and on PROMIS® pain interference [mean change (SD): 3.6 (5.6)], which will be our primary and key secondary outcome, respectively, for the full-scale trial.ConclusionsWe demonstrated the feasibility of participant recruitment, retention, and electronic data collection for conducting a pragmatic clinical trial of chiropractic care in a Veterans Health Administration facility. Using the pilot data and lessons learned, we modified and refined a protocol for a full-scale, multisite, pragmatic, National Institutes of Health-funded randomized trial of multimodal chiropractic care for veterans with chronic LBP that began recruitment in February 2021.Trial registrationClinicalTrials.gov NCT03254719.

Dataset Information

The genetic architecture of pain intensity in a sample of 598,339 U.S. veterans.

Publications

The genetic architecture of pain intensity in a sample of 598,339 U.S. veterans.

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