Table 2.
Publications on (chronic) pain using the UK Biobank cohort.
| Study | Pain phenotype | Design | Finding |
|---|---|---|---|
| Allen et al.1 | AP and CP | CS | Social exclusion and loneliness are associated with pain |
| Atkins et al.5 | CP | CS | Low cardiovascular disease score individuals had less chronic pain |
| Beasley et al.8 | CWP | CS | Relationship between alcohol consumption and reporting of CWP |
| Beasley et al.9 | CWP | MR | Protective effect of alcohol on CWP is not supported |
| Benavides et al.10 | CP | Genetic association | rs1045642 (ABCB1) effect on response to chronic pain treatment with nortriptyline or morphine combo |
| Bortsov et al.16 | BP (acute and chronic) | GWAS | 13 GWS loci for chronic BP, none for acute BP. SNP heritability 4.6% for chronic BP and 0.8% for acute BP |
| Broberg et al.21 | General pain and multisite CP | MR | Bidirectional causal relationship between insomnia and pain |
| Carvalho et al.25 | Musculoskeletal pain | CS and longitudinal | T2D is associated cross-sectionally and longitudinally with shoulder or neck, knee, or hip pain and longitudinally with neck or shoulder pain |
| Carvalho et al.26 | Musculoskeletal pain | CS | Metformin is protective of back, knee, neck or shoulder, and multisite pain |
| Cassidy et al.27 | Drugs prescribed for CP | CS | Opiate and NP medications taken with cardiometabolic medications associated with obesity, increased waist circumference, and hypertension compared with cardiometabolic medications alone |
| Chen et al.29 | Musculoskeletal pain | Longitudinal | Higher number of pain sites associated with risk of all-cause mortality |
| Cox et al.32 | Opioid cessation/CBP | GWAS | PRS for opioid cessation significantly associated with chronic back pain, being a former drinker, and being a former smoker |
| Faber et al.37 | Hip pain | CS | Cam morphology is associated with hip pain |
| Faber et al.38 | Hip pain | CS | Radiographic hip osteoarthritis, total osteocyte area, joint space narrowing and acetabular, and superior and inferior femoral osteophyte areas were all associated with hip pain |
| Faber et al.39 | Hip pain | CS | Osteophytes and joint space narrowing are associated with hip pain |
| Farrell et al.40 | CP | GWAS/PhWAS | Shared genetic signature across 8 chronic pain types and 1492 biopsychosocial traits. 488 traits with causal association with CP |
| Freidin et al.45 | BP | GWAS | 3 loci associated with BP. Pleiotropic effects of genetic risk factors for BP, height, and intervertebral disk problems. Genetic correlations between BP and depression symptoms, neuroticism, sleep disturbance, overweight, and smoking |
| Freidin et al.46 | Chronic BP | GWAS | 2 and 7 GWS loci associated with chronic BP in males and females, respectively |
| Green et al.53 | Frozen shoulder | GWAS/MR | 5 GWS loci associated with frozen shoulder. Diabetes but not obesity is a causal risk factor for frozen shoulder |
| Hanlon et al.55 | CWP | CS | Physical, sexual, and emotional childhood maltreatment and neglect associated with CWP |
| Hastie et al.56 | CP and CWP | Longitudinal | CP and CWP associated with hospital admission for COVID-19. CWP but not CP associated with COVID-19 mortality |
| Jin et al.62 | Oral inflammatory diseases (including mouth ulcer, painful gums, and toothache) | GWAS meta-analysis | 31, 4, and 4 GWS loci associated with mouth ulcer, painful gums, and toothache. 2 novel GWS loci associated with painful gums and toothache |
| Johnston et al.63 | Multisite CP | GWAS/MR | SNP heritability of 10.2%. 39 GWS loci associated with multisite CP. Genetic correlation with psychiatric, autoimmune, and anthropometric traits. Causal effect of multisite CP on MDD |
| Johnston et al.64 | Multisite CP | GWAS | 5 and 10 GWS loci associated with multisite chronic pain in men and women, respectively. Sex-specific gene associations and expression in dorsal root ganglion. Sex-specific association of multisite CP with MDD. Genetic correlation with a range of psychiatric and mood phenotypes |
| Kasher et al.65 | CBP | CS/MR | RA, OP, CRP, BMI, age, and gender associated with CBP. Genetic correlation between CBP and RA and CRP and BMI. CRP causally predicts CBP. Pleiotropy seems to explain relationship between CBP and RA/OP |
| Khoury et al.66 | Single and multisite CP | GWAS | 23 GWS loci associated with multisite CP (none with single site CP) and 9 replicated in HUNT cohort. Axonogenesis in brain tissues is a major contributing pathway |
| Larvin et al.70 | Painful gums | Longitudinal | Higher incidence of CVD and depression in painful gums compared with healthy controls. Increased risk of baseline → CVD → censor and baseline → metabolic → censor disease trajectory in painful gums. The former trajectory has increased the risk of mortality |
| Lobo et al.73 | Chronic multisite musculoskeletal pain | CS/genetic association | Interaction between FKBP5 rs3800373 risk variant and right hippocampal volume associated with chronic multisite musculoskeletal pain. This is mediated by severity of childhood trauma |
| Macfarlane et al.75 | ‘Any pain’, CP, and musculoskeletal pain | CS | Estimates of ‘any pain’, CP, and site-specific musculoskeletal pain prevalence similar between UK Biobank and MUSICIAN/NCDS cohorts |
| Macfarlane et al.76 | CWP | Longitudinal/meta-analysis | CWP associated with excess all-cause mortality as well as excess cancer, cardiovascular, and respiratory-related deaths |
| Macfarlane et al.77 | Opioid use | CS/longitudinal | 5.5% of UK Biobank regularly using opioids. Opioid use is most common in groups of low socioeconomic status. Weak and strong opioids were associated with excess mortality |
| Macfarlane et al.74 | (Chronic) Facial pain | CS | Overall prevalence of facial pain was 1.9%, of which 48% was chronic. Facial pain was more common in women, smokers and associated with psychological distress, low socioeconomic status, low alcohol consumption, and all types of regional pain |
| McIntosh et al.81 | CP | CS/genetic association | PRS for MDD associated with CP in UK Biobank |
| McQueenie et al.83 | CP/CWP | CS | Chronic pain is extremely common across a wide range of LTCs including migraine/headache, IBS, mental health conditions, and diseases of the digestive system. People with ≥4 LTCs 3 and 20 times more likely to have CP and CWP, respectively |
| Meng et al.84 | Knee pain | GWAS | 2 GWS loci (GDF5 and COL27A1) associated with knee pain |
| Meng et al.85 | Headache, facial, neck/shoulder, back, stomach/abdominal, hip and knee pain, and pain all over the body | Genetic association | Positive genetic correlation between all pain phenotypes and depressive symptoms, MDD, and neuroticism, except hip and knee pain |
| Meng et al.86 | Neck and shoulder pain | GWAS | 3 GWS loci associated with neck or shoulder pain. 2 loci (FOXP2 and LINC01572) weakly replicated in an independent cohort. Genetic correlation between neck or shoulder pain and depression, insomnia, and neuroticism |
| Muralidharan et al.88 | Multisite CP | Longitudinal/genetic association | Significant negative correlation between the number of chronic pain sites and age at death in men, but not women. TP53 significantly associated with the number of chronic pain sites in women but not men |
| Nicholl et al.89 | Multisite CP | CS | Individuals who report CP and multisite CP are more likely to have MDD and BD. Relationship between extent of CP and risk of MDD and BD |
| Nicholl et al.90 | CP | CS | CP is more common, and depression is less common in Black and Asian ethnic groups compared with White. Association between presence and extent of CP and depression strongest in minority ethnic groups |
| Pan et al.91 | Multisite musculoskeletal pain (hip, knee, back, and neck/shoulder pain) | CS | Greater number of painful sites consistently associated with poorer physical working capacity and low intensity physical activity compared with moderate or vigorous physical activity |
| Parisien et al.92 | Acute back pain | CS | Elevated risk of acute back pain persistence in subjects taking NSAIDs |
| Patasova et al.94 | Multisite CP and pain control medications (paracetamol, opioids, NSAIDs, and gabapentinoids) | CS/MR | Codeine, tramadol, paracetamol, ibuprofen, gabapentin, and pregabalin all individually associated with hyperopia. Causal effect of multisite CP on hyperopia |
| Rahman et al.96 | CWP | GWAS | 3 GWS loci (RNF123, ATP2C1, and COMT) associated with CWP. Partial genetic correlation between CWP and depressive symptoms, BMI, age of first birth, and years of schooling |
| Rönnegård et al.99 | Acute pain, chronic localised pain, and CWP | Longitudinal | Increasing risk of composite CVD (myocardial infarction, stroke, heart failure, and cardiovascular mortality) in people with increasing pain duration and widespreadness |
| Rosoff et al.100 | Prescription opioid use | MR | Evidence for potential causal associations between prescription opioid use and risk for MDD and ASRD. Genetic liability for MDD associated with increased risk of prescription opioid use |
| Shu et al.103 | LBP | MR | Genetic correlation between LBP and insomnia and daytime sleepiness. Insomnia significantly associated with increased risk of LBP. No reverse causation nor a causal effect of daytime sleepiness on LBP |
| Slade et al.106 | Facial pain | CS | Replication of considerable overlap of facial pain with pain in other parts of body. Greater association with headache and neck pain than pain below the neck |
| Suri et al.114 | CBP | GWAS meta-analysis | GWS locus at SOX5 associated and replicated with CBP. Two GWS loci (CCDC26/GSDMC and DCC) associated with CBP in meta-analysis |
| Tagliaferri et al.115 | Acute back pain, chronic localised back pain, and CBP with other pain sites | CS | People with acute, chronic localised, and CBP with other pain sites have significant differences on brain structure and psychosocial and physical health states than people without pain |
| Tamosauskaite et al.116 | CP | Genetic association | Homozygote HFE C282Y mutations (which is associated with excessive iron absorption) associated with CP in older men. HFE C282Y associated with knee, hip, and back pain in older women |
| Tang et al.117 | BP | MR | Evidence for causal associations between serum iron, ferritin, and transferrin saturation and risk of back pain |
| Verma et al.125 | Multisite CP | Genetic association | EREG (epiregulin) H2 haplotype protective for the presence of at least one CP site, H3 haplotype protective for chronic hip pain, and number of chronic pain sites |
| Walker-Bone et al.129 | CWP | CS | A history of bone fracture is associated with increased risk of CWP in men and women |
| Zhang et al.132 | Stomach/abdominal, multisite CP and neck/shoulder pain | GWAS | In patients with depression, TRIOBP associated with stomach/abdominal pain, SLC9A9 associated with multisite CP, and ADGRF1 associated with neck/shoulder pain |
| Zorina-Lichtenwalter et al.133 | Multisite CP | Genetic association | MC1R variants involved in red hair associated with reduced count of pain conditions |
(C)BP, (chronic) back pain; ABCB1, ATP binding cassette subfamily B member 1; ADGRF1, adhesion G protein-coupled receptor F1; AP, acute pain; ASRD, anxiety and stress-related disorders; ATP2C1, ATPase secretory pathway Ca2+ transporting 1; BD, bipolar disorder; BMI, body mass index; CCDC26, coiled-coil domain-containing 26; COL27A1, collagen Type XXVII alpha 1 chain; COMT, catechol-O-methyltransferase; COVID-19, coronavirus disease 2019; CP, chronic pain; CRP, C-reactive protein; CS, cross-sectional; CVD, cardiovasular disease; CWP, chronic widespread pain; DCC, deleted in colorectal cancer; EREG, epiregulin; FKBP5, FK506 binding protein 5; FOXP2, forkhead box protein P2; GDF5, growth differentiation factor 5; GSDMC, gasdermin C; GWAS, Genome-Wide Association Study; GWS, genome-wide significant; HFE, homeostatic iron regulator; HUNT, The Trøndelag Health Study; IBS, irritable bowel syndrome; LBP, low back pain; LINC01572, long intergenic nonprotein coding RNA 1572; LTC, long-term conditions; MC1R, melanocortin 1 receptor; MDD, major depressive disorder; MR, mendelian randomisation; MUSICIAN, managing unexplained musculoskeletal conditions using traditional and accessible new approaches; NCDS, National Child Development Study; NP, neuropathic pain; NSAID, nonsteroidal anti-inflammatory drug; OP, osteoporosis; PhWAS, Phenome-Wide Association Study; PRS, polygenic risk score; RA, rheumatoid arthritis; RNF123, ring finger protein 123; SLC9A9, solute carrier family 9 member A9; SNP, single nucleotide polymorphism; SOX5, SRY-box transcription factor 5; T2D, type 2 diabetes; TP53, tumor protein P53; TRIOBP, TRIO and F-actin binding protein.