A multi-ancestry genetic study of pain intensity in 598,339 veterans

Toikumo, Sylvanus; Vickers-Smith, Rachel; Jinwala, Zeal; Xu, Hengxing; Saina, Divya; Hartwell, Emily; Pavicic Venegas, Mirko; Sullivan, Kyle; Xu, Ke; Jacobson, Daniel; Gelernter, Joel; Rentsch, Christopher T.; Stahl, Eli; Cheatle, Martin; Zhou, Hang; Waxman, Stephen G.; Justice, Amy; Kember, Rachel; Kranzler, Henry

doi:10.1038/s41591-024-02839-5

Title: A multi-ancestry genetic study of pain intensity in 598,339 veterans

Journal Article · 29 February 2024 · Nature Medicine

DOI: https://doi.org/10.1038/s41591-024-02839-5 · OSTI ID:2324055

Toikumo, Sylvanus ^[1]; Vickers-Smith, Rachel ^[2];

^[3]; Xu, Hengxing ^[3]; Saina, Divya ^[3];

^[1];

^[4];

^[5];

^[4];

^[5];

^[6]; Stahl, Eli ^[7]; Cheatle, Martin ^[3];

^[5];

^[5]; Justice, Amy ^[5];

^[1];

^[1]

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA (United States); Univ. of Pennsylvania, Philadelphia, PA (United States)
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA (United States); Univ. of Kentucky, Lexington, KY (United States)
Univ. of Pennsylvania, Philadelphia, PA (United States)
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
VA Connecticut Healthcare System, West Haven, CT (United States); Yale Univ., New Haven, CT (United States)
VA Connecticut Healthcare System, West Haven, CT (United States); Yale Univ., New Haven, CT (United States); London School of Hygiene & Tropical Medicine (LSHTM) (United Kingdom)
Regeneron Genetics Center, Tarrytown, NY (United States)

Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects the quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids had 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 126 independent genetic loci, 69 of which are new. 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 genome-wide association studies 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, β-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.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE; USDVA; National Institutes of Health (NIH)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 2324055

Journal Information:: Nature Medicine, Journal Name: Nature Medicine Vol. 30; ISSN 1078-8956

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

References (111)

Genetics and prescription opioid use (GaPO): study design for consenting a cohort from an existing biobank to identify clinical and genetic factors influencing prescription opioid use and abuse Troiani, Vanessa; Crist, Richard C.; Doyle, Glenn A. figshare https://doi.org/10.6084/m9.figshare.c.5679674	collection	January 2021
The Penn Medicine BioBank: Towards a Genomics-Enabled Learning Healthcare System to Accelerate Precision Medicine in a Diverse Population Verma, Anurag; Damrauer, Scott M.; Naseer, Nawar Journal of Personalized Medicine, Vol. 12, Issue 12 https://doi.org/10.3390/jpm12121974	journal	November 2022
Prospects of Fine-Mapping Trait-Associated Genomic Regions by Using Summary Statistics from Genome-wide Association Studies Benner, Christian; Havulinna, Aki S.; Järvelin, Marjo-Riitta The American Journal of Human Genetics, Vol. 101, Issue 4 https://doi.org/10.1016/j.ajhg.2017.08.012	journal	October 2017
Genetic risk shared across 24 chronic pain conditions: identification and characterization with genomic structural equation modeling Zorina-Lichtenwalter, Katerina; Bango, Carmen I.; Van Oudenhove, Lukas Pain, Vol. 164, Issue 10 https://doi.org/10.1097/j.pain.0000000000002922	journal	May 2023
Million Veteran Program: A mega-biobank to study genetic influences on health and disease Gaziano, John Michael; Concato, John; Brophy, Mary Journal of Clinical Epidemiology, Vol. 70 https://doi.org/10.1016/j.jclinepi.2015.09.016	journal	February 2016
DGIdb 3.0: a redesign and expansion of the drug–gene interaction database Cotto, Kelsy C.; Wagner, Alex H.; Feng, Yang-Yang Nucleic Acids Research, Vol. 46, Issue D1 https://doi.org/10.1093/nar/gkx1143	journal	November 2017
Genome-wide analysis identifies impaired axonogenesis in chronic overlapping pain conditions Khoury, Samar; Parisien, Marc; Thompson, Scott J. Brain, Vol. 145, Issue 3 https://doi.org/10.1093/brain/awab359	journal	November 2021
Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank Johnston, Keira J. A.; Ward, Joey; Ray, Pradipta R. PLOS Genetics, Vol. 17, Issue 4 https://doi.org/10.1371/journal.pgen.1009428	journal	April 2021
PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations Denny, J. C.; Ritchie, M. D.; Basford, M. A. Bioinformatics, Vol. 26, Issue 9 https://doi.org/10.1093/bioinformatics/btq126	journal	March 2010
A Genome-Wide Association Study Finds Genetic Associations with Broadly-Defined Headache in UK Biobank (N = 223,773) Meng, Weihua; Adams, Mark J.; Hebert, Harry L. EBioMedicine, Vol. 28 https://doi.org/10.1016/j.ebiom.2018.01.023	journal	February 2018
LD Score regression distinguishes confounding from polygenicity in genome-wide association studies Bulik-Sullivan, Brendan K.; Loh, Po-Ru; Finucane, Hilary K. Nature Genetics, Vol. 47, Issue 3 https://doi.org/10.1038/ng.3211	journal	February 2015
Integrative approaches for large-scale transcriptome-wide association studies Gusev, Alexander; Ko, Arthur; Shi, Huwenbo Nature Genetics, Vol. 48, Issue 3 https://doi.org/10.1038/ng.3506	journal	February 2016
Functional mapping and annotation of genetic associations with FUMA Watanabe, Kyoko; Taskesen, Erdogan; van Bochoven, Arjen Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/s41467-017-01261-5	journal	November 2017
Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain Suri, Pradeep; Palmer, Melody R.; Tsepilov, Yakov A. PLOS Genetics, Vol. 14, Issue 9 https://doi.org/10.1371/journal.pgen.1007601	journal	September 2018
Brain-specific genes contribute to chronic but not to acute back pain Bortsov, Andrey V.; Parisien, Marc; Khoury, Samar PAIN Reports, Vol. 7, Issue 5 https://doi.org/10.1097/PR9.0000000000001018	journal	September 2022
Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations Boer, Cindy G.; Hatzikotoulas, Konstantinos; Southam, Lorraine Cell, Vol. 184, Issue 18 https://doi.org/10.1016/j.cell.2021.07.038	journal	September 2021
Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome Greco M., Fabiola Del; Minelli, Cosetta; Sheehan, Nuala A. Statistics in Medicine, Vol. 34, Issue 21 https://doi.org/10.1002/sim.6522	journal	May 2015
Accurate, scalable and integrative haplotype estimation Delaneau, Olivier; Zagury, Jean-François; Robinson, Matthew R. Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13225-y	journal	November 2019
The IASP classification of chronic pain for ICD-11: chronic primary pain Nicholas, Michael; Vlaeyen, Johan W. S.; Rief, Winfried Pain, Vol. 160, Issue 1 https://doi.org/10.1097/j.pain.0000000000001390	journal	January 2019
Agreement Between Electronic Medical Record-based and Self-administered Pain Numeric Rating Scale Goulet, Joseph L.; Brandt, Cynthia; Crystal, Stephen Medical Care, Vol. 51, Issue 3 https://doi.org/10.1097/MLR.0b013e318277f1ad	journal	March 2013
Divergent modulation of pain and anxiety by GABAergic neurons in the ventrolateral periaqueductal gray and dorsal raphe Xie, Linghua; Wu, Hui; Chen, Qing Neuropsychopharmacology, Vol. 48, Issue 10 https://doi.org/10.1038/s41386-022-01520-0	journal	December 2022
The MR-Base platform supports systematic causal inference across the human phenome Hemani, Gibran; Zheng, Jie; Elsworth, Benjamin eLife, Vol. 7 https://doi.org/10.7554/eLife.34408	journal	May 2018
Twin studies of pain Nielsen, Cs; Knudsen, Gp; Steingrímsdóttir, ÓA Clinical Genetics, Vol. 82, Issue 4 https://doi.org/10.1111/j.1399-0004.2012.01938.x	journal	August 2012
Patients with chronic pain exhibit individually unique cortical signatures of pain encoding Mayr, Astrid; Jahn, Pauline; Stankewitz, Anne Human Brain Mapping, Vol. 43, Issue 5 https://doi.org/10.1002/hbm.25750	journal	December 2021
β-blocker prescription is associated with lower cumulative risk of knee osteoarthritis and knee pain consultations in primary care: a propensity score–matched cohort study Nakafero, Georgina; Grainge, Matthew J.; Valdes, Ana M. Rheumatology, Vol. 60, Issue 12 https://doi.org/10.1093/rheumatology/keab234	journal	March 2021
Integrating common and rare genetic variation in diverse human populations Nature, Vol. 467, Issue 7311, p. 52-58 https://doi.org/10.1038/nature09298	journal	September 2010
Genetic mapping of cell type specificity for complex traits Watanabe, Kyoko; Umićević Mirkov, Maša; de Leeuw, Christiaan A. Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-11181-1	journal	July 2019
Topical Sevoflurane: A Novel Treatment for Chronic Pain Caused by Venous Stasis Ulcers Aranke, Mayank; Pham, Cynthia T.; Yilmaz, Melis Anesthesiology and Pain Medicine, Vol. 11, Issue 1 https://doi.org/10.5812/aapm.112832	journal	February 2021
FINEMAP: efficient variable selection using summary data from genome-wide association studies Benner, Christian; Spencer, Chris C. A.; Havulinna, Aki S. Bioinformatics, Vol. 32, Issue 10 https://doi.org/10.1093/bioinformatics/btw018	journal	January 2016
Effects of smoking on patients with chronic pain: a propensity-weighted analysis on the Collaborative Health Outcomes Information Registry Khan, James S.; Hah, Jennifer M.; Mackey, Sean C. Pain, Vol. 160, Issue 10 https://doi.org/10.1097/j.pain.0000000000001631	journal	May 2019
Establishing causal relationships between sleep and adiposity traits using Mendelian randomization Hayes, Bryony L.; Vabistsevits, Marina; Martin, Richard M. Obesity, Vol. 31, Issue 3 https://doi.org/10.1002/oby.23668	journal	February 2023
Next-generation genotype imputation service and methods Das, Sayantan; Forer, Lukas; Schönherr, Sebastian Nature Genetics, Vol. 48, Issue 10 https://doi.org/10.1038/ng.3656	journal	August 2016
Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics Yang, Jian; Hall, John E.; Jose, Pedro A. Pharmacology & Therapeutics, Vol. 239 https://doi.org/10.1016/j.pharmthera.2022.108194	journal	November 2022
The Molecular Signatures Database Hallmark Gene Set Collection Liberzon, Arthur; Birger, Chet; Thorvaldsdóttir, Helga Cell Systems, Vol. 1, Issue 6 https://doi.org/10.1016/j.cels.2015.12.004	journal	December 2015
Evaluation of Increases in Drug Overdose Mortality Rates in the US by Race and Ethnicity Before and During the COVID-19 Pandemic Friedman, Joseph R.; Hansen, Helena JAMA Psychiatry, Vol. 79, Issue 4 https://doi.org/10.1001/jamapsychiatry.2022.0004	journal	April 2022
Efficacy and Safety of Multiple Dosages of Fostamatinib in Adult Patients With Rheumatoid Arthritis: A Systematic Review and Meta-Analysis Kang, Yaqi; Jiang, Xinrui; Qin, Dalian Frontiers in Pharmacology, Vol. 10 https://doi.org/10.3389/fphar.2019.00897	journal	August 2019
Genome-wide association studies Uffelmann, Emil; Huang, Qin Qin; Munung, Nchangwi Syntia Nature Reviews Methods Primers, Vol. 1, Issue 1 https://doi.org/10.1038/s43586-021-00056-9	journal	August 2021
Association of Beta‐Blocker Use With Less Prevalent Joint Pain and Lower Opioid Requirement in People With Osteoarthritis Valdes, Ana M.; Abhishek, Abhishek; Muir, Kenneth Arthritis Care & Research, Vol. 69, Issue 7 https://doi.org/10.1002/acr.23091	journal	June 2017
A genome-wide association study finds genetic variants associated with neck or shoulder pain in UK Biobank Meng, Weihua; Chan, Brian W.; Harris, Cameron Human Molecular Genetics, Vol. 29, Issue 8 https://doi.org/10.1093/hmg/ddaa058	journal	April 2020
Reliability and responsivity of pain intensity scales in individuals with chronic pain Euasobhon, Pramote; Atisook, Raviwon; Bumrungchatudom, Kulsiri Pain, Vol. 163, Issue 12 https://doi.org/10.1097/j.pain.0000000000002692	journal	May 2022
Genome-wide association study of knee pain identifies associations with GDF5 and COL27A1 in UK Biobank Meng, Weihua; Adams, Mark J.; Palmer, Colin N. A. Communications Biology, Vol. 2, Issue 1 https://doi.org/10.1038/s42003-019-0568-2	journal	August 2019
GCTA: A Tool for Genome-wide Complex Trait Analysis Yang, Jian; Lee, S. Hong; Goddard, Michael E. The American Journal of Human Genetics, Vol. 88, Issue 1 https://doi.org/10.1016/j.ajhg.2010.11.011	journal	January 2011
A global reference for human genetic variation Consortium, The 1000 Genomes Project; Auton, Adam; Abecasis, Gonçalo R. Nature, Vol. 526, Issue 7571, p. 68-74 https://doi.org/10.1038/nature15393	journal	January 2015
A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache Jackson, Jeffrey L.; Cogbill, Elizabeth; Santana-Davila, Rafael PLOS ONE, Vol. 10, Issue 7 https://doi.org/10.1371/journal.pone.0130733	journal	July 2015
Reliability of DSM-IV diagnostic criteria using the semi-structured assessment for drug dependence and alcoholism (SSADDA) Pierucci-Lagha, Amira; Gelernter, Joel; Chan, Grace Drug and Alcohol Dependence, Vol. 91, Issue 1 https://doi.org/10.1016/j.drugalcdep.2007.04.014	journal	November 2007
Efficacy of Opioids for Chronic Pain Ballantyne, Jane C.; Shin, Naomi S. The Clinical Journal of Pain, Vol. 24, Issue 6 https://doi.org/10.1097/AJP.0b013e31816b2f26	journal	July 2008
Phenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample Kember, Rachel L.; Hartwell, Emily E.; Xu, Heng Biological Psychiatry, Vol. 93, Issue 6 https://doi.org/10.1016/j.biopsych.2022.08.010	journal	March 2023
Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions Tsepilov, Yakov A.; Freidin, Maxim B.; Shadrina, Alexandra S. Communications Biology, Vol. 3, Issue 1 https://doi.org/10.1038/s42003-020-1051-9	journal	June 2020
Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain Rahman, Md Shafiqur; Winsvold, Bendik S.; Chavez Chavez, Sergio O. Annals of the Rheumatic Diseases, Vol. 80, Issue 9 https://doi.org/10.1136/annrheumdis-2020-219624	journal	April 2021
Complex-Traits Genetics Virtual Lab: A community-driven web platform for post-GWAS analyses Cuellar-Partida, Gabriel; Lundberg, Mischa; Kho, Pik Fang bioRxiv https://doi.org/10.1101/518027	preprint	May 2019
Human pain genetics database: a resource dedicated to human pain genetics research Meloto, Carolina B.; Benavides, Rodrigo; Lichtenwalter, Ryan N. Pain, Vol. 159, Issue 4 https://doi.org/10.1097/j.pain.0000000000001135	journal	December 2017
Functional brain reconfiguration during sustained pain Lee, Jae-Joong; Lee, Sungwoo; Lee, Dong Hee eLife, Vol. 11 https://doi.org/10.7554/eLife.74463	journal	September 2022
Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk Rajarajan, Prashanth; Borrman, Tyler; Liao, Will Science, Vol. 362, Issue 6420 https://doi.org/10.1126/science.aat4311	journal	December 2018
Identification and functional evaluation of GRIA1 missense and truncation variants in individuals with ID: An emerging neurodevelopmental syndrome Ismail, Vardha; Zachariassen, Linda G.; Godwin, Annie The American Journal of Human Genetics, Vol. 109, Issue 7 https://doi.org/10.1016/j.ajhg.2022.05.009	journal	July 2022
METAL: fast and efficient meta-analysis of genomewide association scans Willer, C. J.; Li, Y.; Abecasis, G. R. Bioinformatics, Vol. 26, Issue 17 https://doi.org/10.1093/bioinformatics/btq340	journal	July 2010
The Role of GABA in the Mediation and Perception of Pain Enna, S. J.; McCarson, Kenneth E. Advances in Pharmacology, p. 1-27 https://doi.org/10.1016/S1054-3589(06)54001-3	book	January 2006
Genetic control of RNA splicing and its distinct role in complex trait variation Qi, Ting; Wu, Yang; Fang, Hailing Nature Genetics, Vol. 54, Issue 9 https://doi.org/10.1038/s41588-022-01154-4	journal	August 2022
Drug repurposing: progress, challenges and recommendations Pushpakom, Sudeep; Iorio, Francesco; Eyers, Patrick A. Nature Reviews Drug Discovery, Vol. 18, Issue 1 https://doi.org/10.1038/nrd.2018.168	journal	October 2018
Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders Yang, Chengran; Farias, Fabiana H. G.; Ibanez, Laura Nature Neuroscience, Vol. 24, Issue 9 https://doi.org/10.1038/s41593-021-00886-6	journal	July 2021
Gene expression elucidates functional impact of polygenic risk for schizophrenia Fromer, Menachem; Roussos, Panos; Sieberts, Solveig K. Nature Neuroscience, Vol. 19, Issue 11 https://doi.org/10.1038/nn.4399	journal	September 2016
ChEMBL: a large-scale bioactivity database for drug discovery Gaulton, A.; Bellis, L. J.; Bento, A. P. Nucleic Acids Research, Vol. 40, Issue D1 https://doi.org/10.1093/nar/gkr777	journal	September 2011
The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises Raja, Srinivasa N.; Carr, Daniel B.; Cohen, Milton Pain, Vol. 161, Issue 9 https://doi.org/10.1097/j.pain.0000000000001939	journal	September 2020
Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains Geisheker, Madeleine R.; Heymann, Gabriel; Wang, Tianyun Nature Neuroscience, Vol. 20, Issue 8 https://doi.org/10.1038/nn.4589	journal	June 2017
Hypertension prevalence and diminished blood pressure–related hypoalgesia in individuals reporting chronic pain in a general population: The Tromsø Study Olsen, Roy Bjørkholt; Bruehl, Stephen; Nielsen, Christopher Sivert Pain, Vol. 154, Issue 2 https://doi.org/10.1016/j.pain.2012.10.020	journal	February 2013
Reduced insular γ‐aminobutyric acid in fibromyalgia Foerster, Bradley R.; Petrou, Myria; Edden, Richard A. E. Arthritis & Rheumatism, Vol. 64, Issue 2 https://doi.org/10.1002/art.33339	journal	January 2012
Elevated GABA level in the precuneus and its association with pain intensity in patients with postherpetic neuralgia: An initial proton magnetic resonance spectroscopy study Wu, Xiaojuan; Yuan, Junpeng; Yang, Yang European Journal of Radiology, Vol. 157 https://doi.org/10.1016/j.ejrad.2022.110568	journal	December 2022
Diagnostic reliability of the Semi-structured Assessment for Drug Dependence and Alcoholism (SSADDA) Pierucci-Lagha, Amira; Gelernter, Joel; Feinn, Richard Drug and Alcohol Dependence, Vol. 80, Issue 3 https://doi.org/10.1016/j.drugalcdep.2005.04.005	journal	December 2005
Genome-wide association study of multisite chronic pain in UK Biobank Johnston, Keira J. A.; Adams, Mark J.; Nicholl, Barbara I. PLOS Genetics, Vol. 15, Issue 6 https://doi.org/10.1371/journal.pgen.1008164	journal	June 2019
Second-generation PLINK: rising to the challenge of larger and richer datasets Chang, Christopher C.; Chow, Carson C.; Tellier, Laurent CAM GigaScience, Vol. 4, Issue 1 https://doi.org/10.1186/s13742-015-0047-8	journal	February 2015
Shared mechanisms across the major psychiatric and neurodegenerative diseases Wingo, Thomas S.; Liu, Yue; Gerasimov, Ekaterina S. Nature Communications, Vol. 13, Issue 1 https://doi.org/10.1038/s41467-022-31873-5	journal	July 2022
Insight into the genetic architecture of back pain and its risk factors from a study of 509,000 individuals Freidin, Maxim B.; Tsepilov, Yakov A.; Palmer, Melody Pain, Vol. 160, Issue 6 https://doi.org/10.1097/j.pain.0000000000001514	journal	February 2019
Polygenic prediction via Bayesian regression and continuous shrinkage priors Ge, Tian; Chen, Chia-Yen; Ni, Yang Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-09718-5	journal	April 2019
Orienting the causal relationship between imprecisely measured traits using GWAS summary data Hemani, Gibran; Tilling, Kate; Davey Smith, George PLOS Genetics, Vol. 13, Issue 11 https://doi.org/10.1371/journal.pgen.1007081	journal	November 2017
Genetic studies of human neuropathic pain conditions: a review Zorina-Lichtenwalter, Katerina; Parisien, Marc; Diatchenko, Luda Pain, Vol. 159, Issue 3 https://doi.org/10.1097/j.pain.0000000000001099	journal	November 2017
Measuring pain care quality in the Veterans Health Administration primary care setting Luther, Stephen L.; Finch, Dezon K.; Bouayad, Lina Pain, Vol. 163, Issue 6 https://doi.org/10.1097/j.pain.0000000000002477	journal	September 2021
A consideration of differences in pain scales used in clinical trials Farrar, John T. Pain, Vol. 163, Issue 12 https://doi.org/10.1097/j.pain.0000000000002691	journal	May 2022
Informed Consent in Opioid Therapy: A Potential Obligation and Opportunity Cheatle, Martin D.; Savage, Seddon R. Journal of Pain and Symptom Management, Vol. 44, Issue 1 https://doi.org/10.1016/j.jpainsymman.2011.06.015	journal	July 2012
Intrinsic Brain Connectivity in Chronic Pain: A Resting-State fMRI Study in Patients with Rheumatoid Arthritis Flodin, Pär; Martinsen, Sofia; Altawil, Reem Frontiers in Human Neuroscience, Vol. 10 https://doi.org/10.3389/fnhum.2016.00107	journal	March 2016
A computational tool (H-MAGMA) for improved prediction of brain-disorder risk genes by incorporating brain chromatin interaction profiles Sey, Nancy Y. A.; Hu, Benxia; Mah, Won Nature Neuroscience, Vol. 23, Issue 4 https://doi.org/10.1038/s41593-020-0603-0	journal	March 2020
Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain Rahman, Shafiqur; Winsvold, Bendik S.; Chavez, S. O. Chavez Zenodo https://doi.org/10.5281/zenodo.4459546	dataset	January 2021
Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets Zhu, Zhihong; Zhang, Futao; Hu, Han Nature Genetics, Vol. 48, Issue 5 https://doi.org/10.1038/ng.3538	journal	March 2016
minimac2: faster genotype imputation Fuchsberger, Christian; Abecasis, Gonçalo R.; Hinds, David A. Bioinformatics, Vol. 31, Issue 5 https://doi.org/10.1093/bioinformatics/btu704	journal	October 2014
Comparative transcriptome profiling of the human and mouse dorsal root ganglia: an RNA-seq–based resource for pain and sensory neuroscience research Ray, Pradipta; Torck, Andrew; Quigley, Lilyana Pain, Vol. 159, Issue 7 https://doi.org/10.1097/j.pain.0000000000001217	journal	March 2018
Genetics and prescription opioid use (GaPO): study design for consenting a cohort from an existing biobank to identify clinical and genetic factors influencing prescription opioid use and abuse Troiani, Vanessa; Crist, Richard C.; Doyle, Glenn A. BMC Medical Genomics, Vol. 14, Issue 1 https://doi.org/10.1186/s12920-021-01100-z	journal	October 2021
Genetic correlations between pain phenotypes and depression and neuroticism Meng, Weihua; Adams, Mark J.; Reel, Parminder European Journal of Human Genetics, Vol. 28, Issue 3 https://doi.org/10.1038/s41431-019-0530-2	journal	October 2019
Prevalence of chronic pain among adults in the United States Yong, R. Jason; Mullins, Peter M.; Bhattacharyya, Neil Pain, Vol. 163, Issue 2 https://doi.org/10.1097/j.pain.0000000000002291	journal	April 2021
Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis Finnerup, Nanna B.; Attal, Nadine; Haroutounian, Simon The Lancet Neurology, Vol. 14, Issue 2 https://doi.org/10.1016/S1474-4422(14)70251-0	journal	February 2015
Providing chronic pain management in the “Fifth Vital Sign” Era: Historical and treatment perspectives on a modern-day medical dilemma Tompkins, D. Andrew; Hobelmann, J. Greg; Compton, Peggy Drug and Alcohol Dependence, Vol. 173 https://doi.org/10.1016/j.drugalcdep.2016.12.002	journal	April 2017
The NIH Roadmap Epigenomics Mapping Consortium Bernstein, Bradley E.; Stamatoyannopoulos, John A.; Costello, Joseph F. Nature Biotechnology, Vol. 28, Issue 10 https://doi.org/10.1038/nbt1010-1045	journal	October 2010
Metabotropic receptors for glutamate and GABA in pain Goudet, Cyril; Magnaghi, Valerio; Landry, Marc Brain Research Reviews, Vol. 60, Issue 1 https://doi.org/10.1016/j.brainresrev.2008.12.007	journal	April 2009
Using multiple genetic variants as instrumental variables for modifiable risk factors Palmer, Tom M.; Lawlor, Debbie A.; Harbord, Roger M. Statistical Methods in Medical Research, Vol. 21, Issue 3 https://doi.org/10.1177/0962280210394459	journal	January 2011
Moving Beyond Pain as the Fifth Vital Sign and Patient Satisfaction Scores to Improve Pain Care in the 21st Century Scher, Clara; Meador, Lauren; Van Cleave, Janet H. Pain Management Nursing, Vol. 19, Issue 2 https://doi.org/10.1016/j.pmn.2017.10.010	journal	April 2018
Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics Giambartolomei, Claudia; Vukcevic, Damjan; Schadt, Eric E. PLoS Genetics, Vol. 10, Issue 5 https://doi.org/10.1371/journal.pgen.1004383	journal	May 2014
Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia Dong, Weilai; Jin, Sheng Chih; Allocco, August iScience, Vol. 23, Issue 10 https://doi.org/10.1016/j.isci.2020.101552	journal	October 2020
Harmonizing Genetic Ancestry and Self-identified Race/Ethnicity in Genome-wide Association Studies Fang, Huaying; Hui, Qin; Lynch, Julie The American Journal of Human Genetics, Vol. 105, Issue 4 https://doi.org/10.1016/j.ajhg.2019.08.012	journal	October 2019
Genome wide association joint analysis reveals 99 risk loci for pain susceptibility and pleiotropic relationships with psychiatric, metabolic, and immunological traits Mocci, Evelina; Ward, Kathryn; Perry, James A. PLOS Genetics, Vol. 19, Issue 10 https://doi.org/10.1371/journal.pgen.1010977	journal	October 2023
Omics approaches to discover pathophysiological pathways contributing to human pain Diatchenko, Luda; Parisien, Marc; Jahangiri Esfahani, Sahel Pain, Vol. 163, Issue S1 https://doi.org/10.1097/j.pain.0000000000002726	journal	July 2022
Mendelian Randomisation and Causal Inference in Observational Epidemiology Sheehan, Nuala A.; Didelez, Vanessa; Burton, Paul R. PLoS Medicine, Vol. 5, Issue 8 https://doi.org/10.1371/journal.pmed.0050177	journal	August 2008
Genotyping Array Design and Data Quality Control in the Million Veteran Program Hunter-Zinck, Haley; Shi, Yunling; Li, Man The American Journal of Human Genetics, Vol. 106, Issue 4 https://doi.org/10.1016/j.ajhg.2020.03.004	journal	April 2020
Transethnic Genetic-Correlation Estimates from Summary Statistics Brown, Brielin C.; Ye, Chun Jimmie; Price, Alkes L. The American Journal of Human Genetics, Vol. 99, Issue 1 https://doi.org/10.1016/j.ajhg.2016.05.001	journal	July 2016
The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource Sollis, Elliot; Mosaku, Abayomi; Abid, Ala Nucleic Acids Research, Vol. 51, Issue D1 https://doi.org/10.1093/nar/gkac1010	journal	November 2022
Altered neurochemical coupling in the occipital cortex in migraine with visual aura Bridge, Holly; Stagg, Charlotte J.; Near, Jamie Cephalalgia, Vol. 35, Issue 11 https://doi.org/10.1177/0333102414566860	journal	January 2015
Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types Finucane, Hilary K.; Reshef, Yakir A.; Anttila, Verneri Nature Genetics, Vol. 50, Issue 4 https://doi.org/10.1038/s41588-018-0081-4	journal	April 2018
The druggable genome and support for target identification and validation in drug development Finan, Chris; Gaulton, Anna; Kruger, Felix A. Science Translational Medicine, Vol. 9, Issue 383 https://doi.org/10.1126/scitranslmed.aag1166	journal	March 2017
Partitioning heritability by functional annotation using genome-wide association summary statistics Finucane, Hilary K.; Bulik-Sullivan, Brendan; Gusev, Alexander Nature Genetics, Vol. 47, Issue 11 https://doi.org/10.1038/ng.3404	journal	September 2015
Estimating the causal effect of frailty index on vestibular disorders: A two-sample Mendelian randomization Xiao, Gui; Wang, Hu; Hu, Jiaji Frontiers in Neuroscience, Vol. 16 https://doi.org/10.3389/fnins.2022.990682	journal	August 2022
MAGMA: Generalized Gene-Set Analysis of GWAS Data de Leeuw, Christiaan A.; Mooij, Joris M.; Heskes, Tom PLOS Computational Biology, Vol. 11, Issue 4 https://doi.org/10.1371/journal.pcbi.1004219	journal	April 2015
Prevalence of pain in community-dwelling older adults with hypertension in the United States Li, Chao-Yi; Lin, Wei-Cheng; Lu, Ching-Yen Scientific Reports, Vol. 12, Issue 1 https://doi.org/10.1038/s41598-022-12331-0	journal	May 2022
Responding to the opioid crisis in North America and beyond: recommendations of the Stanford–Lancet Commission Humphreys, Keith; Shover, Chelsea L.; Andrews, Christina M. The Lancet, Vol. 399, Issue 10324 https://doi.org/10.1016/S0140-6736(21)02252-2	journal	February 2022
Animal models of pain: Diversity and benefits Abboud, Cynthia; Duveau, Alexia; Bouali-Benazzouz, Rabia Journal of Neuroscience Methods, Vol. 348 https://doi.org/10.1016/j.jneumeth.2020.108997	journal	January 2021
Chronic Pain and the Emotional Brain: Specific Brain Activity Associated with Spontaneous Fluctuations of Intensity of Chronic Back Pain Baliki, Marwan N.; Chialvo, Dante R.; Geha, Paul Y. The Journal of Neuroscience, Vol. 26, Issue 47 https://doi.org/10.1523/JNEUROSCI.3576-06.2006	journal	November 2006

Similar Records

A genome-wide association study of suicide attempts in the million veterans program identifies evidence of pan-ancestry and ancestry-specific risk loci

Journal Article · 2022 · Molecular Psychiatry · OSTI ID:1876345

Kimbrel, Nathan A.; Ashley-Koch, Allison E.; Qin, Xue J.; +19 more

Prevalence of Neuropathic Pain in Radiotherapy Oncology Units

Journal Article · 2011 · International Journal of Radiation Oncology, Biology and Physics · OSTI ID:21587741

Manas, Ana; Monroy, Jose Luis; Ramos, Avelino Alia; +4 more

High-throughput behavioral phenotyping of drug and alcohol susceptibility traits in the expanded panel of BXD recombinant inbred strains

Journal Article · 2010 · Genes, Brain and Behavior · OSTI ID:986771

Philip, Vivek M; Ansah, T; Blaha, C; +6 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
pain
risk factors

Title: A multi-ancestry genetic study of pain intensity in 598,339 veterans

Citation Formats

References (111)

Similar Records

Related Subjects