The association of lumbar intervertebral disc degeneration with low back pain is modified by underlying genetic propensity to pain.

BACKGROUND CONTEXT: Associations between magnetic resonance imaging (MRI)-detected lumbar intervertebral disc degeneration (LDD) and LBP are often of modest magnitude. This association may be larger in specific patient subgroups. PURPOSE: To examine whether the association between LDD and LBP is modified by underlying genetic predispositions to pain. STUDY DESIGN: Cross-sectional study in UK Biobank (UKB) and TwinsUK. PATIENT SAMPLES: A genome-wide association study (GWAS) of the number of anatomical chronic pain locations was conducted in 347,538 UKB participants. The GWAS was used to develop a genome-wide polygenic risk score (PRS) in a holdout sample of 30,000 UKB participants. The PRS model was then used in analyses of 645 TwinsUK participants with standardized LDD MRI assessments. OUTCOME MEASURES: Ever having had LBP associated with disability lasting ≥1 month (LBP1). METHODS: Using the PRS as a proxy for "genetically-predicted propensity to pain", we stratified TwinsUK participants into PRS quartiles. A "basic" model examined the association between an LDD summary score (LSUM) and LBP1, adjusting for covariates. A "fully-adjusted" model also adjusted for PRS quartile and LSUM x PRS quartile interaction terms. RESULTS: In the basic model, the odds ratio (OR) of LBP1 was 1.8 per standard deviation of LSUM (95% confidence interval [CI] 1.4 -2.3). In the fully-adjusted model, there was a statistically significant LSUM-LBP1 association in quartile 4, the highest PRS quartile (OR = 2.5 [95% CI 1.7-3.7], p=2.6×10-6), and in quartile 3 (OR=2.0, [95% CI 1.3-3.0]; p=0.002), with small-magnitude and/or non-significant associations in the lowest two PRS quartiles. PRS quartile was a significant effect modifier of the LSUM-LBP1 association (interaction p≤0.05). CONCLUSIONS: Genetically-predicted propensity to pain modifies the LDD-LBP association, with the strongest association present in people with the highest genetic propensity to pain. Lumbar MRI findings may have stronger connections to LBP in specific subgroups of people.

Treatment response in rheumatoid arthritis is predicted by the microbiome: a large observational study in UK DMARD-naïve patients.

OBJECTIVES: Disease-modifying antirheumatic drugs (DMARDs) are first line treatment in rheumatoid arthritis (RA). Treatment response to DMARDs is patient-specific, dose efficacy is difficult to predict and long-term results variable. The gut microbiota are known to play a pivotal role in prodromal and early-disease RA, manifested by Prevotella spp. enrichment. The clinical response to therapy may be mediated by microbiota, and large-scale studies assessing the microbiome are few. This study assessed whether microbiome signals were associated with, and predictive of, patient response to DMARD-treatment. Accurate early identification of those who will respond poorly to DMARD therapy would allow selection of alternative treatment (e.g. biologic therapy), and potentially improve patient outcome. METHODS: A multicentre, longitudinal, observational study of stool- and saliva microbiome was performed in DMARD-naïve, newly diagnosed RA patients during introduction of DMARD treatment. Clinical data and samples were collected at baseline (n = 144) in DMARD-naïve patients and at six weeks (n = 117) and 12 weeks (n = 95) into DMARD-therapy. Samples collected (n = 365 stool, n = 365 saliva) underwent shotgun sequencing. Disease activity measures were collected at each timepoint and minimal clinically important improvement determined. RESULTS: In total, 26 stool microbes were found to decrease in those manifesting a minimal clinically important improvement. Prevotella spp. and Streptococcus spp. were the predominant taxa to decline following six weeks and 12 weeks of DMARDs, respectively. Furthermore, baseline microbiota of DMARD-naïve patients were indicative of future response. CONCLUSION: DMARDs appear to restore a perturbed microbiome to a eubiotic state. Moreover, microbiome status can be used to predict likelihood of patient response to DMARD.

Modic change is associated with increased BMI but not autoimmune diseases in TwinsUK.

PURPOSE: Low back pain (LBP) is one of the largest causes of morbidity worldwide. The aetiology of LBP is complex, and many factors contribute to the onset. Bone marrow lesions within the vertebra adjacent to an intervertebral degenerate disc named Modic change (MC) have been suggested as a diagnostic subgroup of LBP. Autoimmune response has been proposed to be one of the causes that promote the development of MC. The aim of the current investigation is to assess prevalence and severity of MC and LBP in participants with an autoimmune disease diagnosis in a well-documented cohort of adult twin volunteers. METHODS: Multivariate generalized mixed linear models (GLMM) were implemented in order to calculate the association between having an autoimmune disorder and MC prevalence, width and severe and disabling LBP. The model was corrected for family structure as well as for covariates such as age, BMI and smoking. RESULTS: No association was found between diagnosis of autoimmune disorder and MC. Interestingly, BMI was independently associated with MC width but not to MC prevalence. These results help to shed light on the relationship between MC and autoimmunity as well as the role of BMI in the development of the lesions. CONCLUSION: This study is the first to examine autoimmune disorders and MC prevalence in a large, population-based female cohort. The study was well powered to detect a small effect. No association was found between having a diagnosis of one or more autoimmune conditions and MC prevalence, width or LBP.

How well does a wellbeing measure predict psychiatric 'caseness' as well as suicide risk and self-harm in adolescents?

Screening for psychiatric disorders may be hampered by traditional measures that increase participant burden and elicit negative responses via denial and social desirability biases. This study examined the utility of a wellbeing measure to identify psychopathology and suicide risk in adolescent participants. 1,579 students from Sydney schools participated in a survey which assessed wellbeing using the Satisfaction With Life Scale (SWLS) as well as psychiatric disorders and suicide risk. Results showed that low scores on the SWLS discriminated adolescents who had experienced a psychiatric condition or suicidality from those not so assigned. Specifically, students with no psychiatric diagnosis yielded a mean SWLS score of 28.0 while for those assigned a diagnosis, mean scores ranged from 19.4-3.0 across the various psychiatric conditions. Students who reported any suicidal ideation yielded a mean SWLS score of 22.7, and those with a current suicidal plan yielded a mean score of 17.7. We derived SWLS cut-off scores for predicting psychiatric caseness and suicidality but established that they had low positive predictive power. The SWLS therefore appears to provide a limited proxy measure of the chance of a psychiatric disorder or psychological distress, and might usefully complement more direct measures of such states.

The validity of a food frequency questionnaire as a measure of PUFA status in pregnancy.

BACKGROUND: Nutritional studies have found conflicting evidence regarding the ability of Food Frequency Questionnaires (FFQs) to demonstrate convergent validity with tissue content of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs). We therefore sought to assess the convergent validity of a FFQ strategy when compared with a blood biomarker of PUFA levels in a sample of pregnant women. METHOD: A previously validated PUFA FFQ was completed by 895 pregnant women and compared to erythrocyte membrane of six PUFA variables. RESULTS: Four of the six correlations were found to be formally significant, however two of these demonstrated minimal associational strength. Moderate-high correlations between the FFQ-derived PUFA intake estimates and blood biomarker PUFA levels were shown only for eicosapentaenoic acid (EPA; 0.55) and docosahexaenoic acid (DHA; 0.61). CONCLUSIONS: Overall, the correlations were lower than those found in general population studies. Findings suggest biological estimates, such as blood samples, may be most appropriate to measure PUFA levels above indirect strategies such as an FFQ in this population. The results, if an indirect strategy is unavoidable, indicate specific PUFAs where an FFQ strategy may be most informative.