Objective. Low back pain (LBP) is a common debilitating condition with great socioeconomic impact. Identifying individuals at risk of LBP is challenging. We have shown IgG N-glycans are associated with LBP. Herewith, we used polygenic risk scores (PRS) from IgG-glycome to test predictability for LBP. Methods. Clusters of IgG-glycans were identified using weighted correlation network approach in TwinsUK (n = 4246). Genome-wide association studies were carried out for the clusters and top associated SNPs (p<5e-8) were extracted. Weighted PRS was calculated as the sum of the number of copies of effect allele from GWAS multiplied by their effect size using the UK Biobank data (n = 350000). The predictive capacity of the PRS for back pain in UK Biobank was estimated using logistic regression. Results. Multiple SNPs were found to be associated with the glycan clusters near genes known to be involved in glycosylation and the inflammatory response (e.g. ST6GAL1, B4GALT1, FUT8). A total of 175 SNPs was used to calculate weighted PRS. In UK Biobank the PRS was a statically significant, but poor, predictor of the risk of back pain (β = 0.126±0.050, p = 0.015, R. 2. = 2.6e-5). The SNPs on chromosome 14 in regulatory regions of FUT8 gene, one of the key governors of core fucosylation, were found to be significantly associated with back pain in UK Biobank (FDR-adjusted p-value < 0.05). Conclusions. These pilot data suggest that genetic component of glycosylation may be associated with the risk of LBP; however, its predictive ability is poor. Conflict of Interest: YSA is a co-owner of Maatschap PolyOmica. GL is a founder and CEO of Genos Glycoscience Research Laboratory. MBF and FMKW declare no conflict of interests. Sources of Funding: The research has been supported by the EC FP7 project PainOmics (grant agreement #602736) and conducted using the UK Biobank Resource (project # 18219)

Purpose. Back pain is the primary cause of disability worldwide yet surprisingly little is known of the underlying pathobiology. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and UK Biobank were studied. Methods. CBP cases were defined as reporting back pain present for ≥3–6 months; non-cases were included as comparisons (“controls”). Each cohort conducted genotyping followed by imputation. GWAS used logistic regression with additive genetic effects adjusting for age, sex, study-specific covariates, and population substructure. Suggestive (p<5×10. –7. ) & genome-wide significant (p<5×10. –8. ) variants were carried forward for replication in an independent sample of UK Biobank participants. Discovery sample n = 158,025 individuals, including 29,531 CBP cases. Results. Genome-wide significant association was found for intron variant rs12310519 in SOX5 (OR=1.08, p=7.2×10. −10. ). This was replicated in the independent sample n = 283,752, comprising 50,915 cases (OR 1.06, p=5.3×10. −11. ); in joint meta-analysis OR=1.07, p=4.5×10. −19. exceeding genome-wide significance. We found three other suggestive associations in discovery, two of which exceeded genome-wide significance in joint meta-analysis: an intergenic variant rs7833174 located between CCDC26 and GSDMC (OR 1.05, p=4.4×10. −13. ), and an intron variant, rs4384683, in DCC (OR 0.97, p=2.4×10. −10. ). Conclusion. We have identified and replicated a genetic locus associated with CBP (SOX5). We also identified 2 other loci that reached genome-wide significance in a 2-stage joint meta-analysis (CCDC26/GSDMC and DCC) which will shed light on the pathogenic mechanisms underlying CBP. Conflicts of interest: YA and LK are owners of Maatschap PolyOmica. This study was supported by the European Community's Seventh Framework Programme funded project PainOmics (Grant agreement n. 602736) and conducted using the UK Biobank Resource (project # 18219). CHARGE and other cohort-specific funding sources to be submitted- see below

Background. The association between lumbar intervertebral disc degeneration (LDD) and low back pain (LBP) is modest. We have recently shown that genetic propensity to pain is an effect modifier of the LDD-LBP relationship when LDD is defined as a summary score of LDD (LSUM), suggesting the association may be driven by individuals with the greatest genetic predisposition to pain. This study examined the association between individual spine magnetic resonance imaging (MRI)-determined LDD features and LBP in subgroups defined by genetic predisposition to pain. Method. We developed a polygenic risk score (PRS) for “genetic propensity to pain” defined as the number of non-back pain locations (head, face, neck/shoulder, stomach/abdomen, hip, and knee) with duration ≥3 months in 377,538 UK Biobank participants of European ancestry. This PRS was used to stratify TwinsUK MRI samples (n=645) into four strata of genetic propensity to pain. We examined the association between LBP and MRI features of lumbar disc height, disc signal intensity, disc bulge, and osteophytes with adjustments for age, sex, PRS strata, interaction terms for each MRI feature x PRS strata, and twin status. Results. We found significant effect modification of the LDD-LBP relationship by genetic propensity to pain for the lumbar MRI features of disc height (p=0.03 for the interaction term with highest quartile of genetically-predicted propensity to pain) and disc signal intensity (p=0.001), but not for disc bulge and osteophytes. Conclusion. Genetic propensity to pain modifies the association between individual LDD features and LBP and should be considered in LBP clinical studies. Conflicts of interest. No conflicts of interest. Sources of funding. No funding obtained. Acknowledgement. UKBB data were obtained under the project #18219. This paper is submitted to the Spine journal and is under review

Background. Lateral lumbar spine statistical shape models (SSM) have been used previously to describe associations with osteoarthritis and back pain. However, associations with factors such as osteoporosis, menopause and parity have not been explored. Methods and Results. A 143-point SSM, describing L1 to the top of L5, was applied to lateral spine iDXA scans from UK Biobank. Associations with self-reported osteoporosis, menopause, parity and back pain and the first 10 modes of variation were examined using adjusted binary logistic regression or linear regression (adjusted for age, height, weight and total spine BMD). We report odds ratios with 95% confidence intervals for each standard deviation change in mode. Complete data were available for 2494 women. Mean age was 61.5 (± 7.4) years. 1369 women reported going through menopause, 96 women self-reported osteoporosis and 339 women reported chronic back pain. 80% of women reported at least 1 live birth. Lumbar spine shape was not associated with back pain in this cohort. Two modes were associated with menopause (modes 1 & 2), 1 mode with parity (mode 1) and 2 modes with osteoporosis (modes 3 & 5). Mode 1 (43.6% total variation), describing lumbar curvature was positively associated with both menopause [OR 1.15 95% CI 1.00–1.33, p=0.05] and parity [OR 1.058 95% CI 1.03–1.0, p=0.01]. Mode 3, describing decreased vertebral height was positively associated with osteoporosis [OR 1.40 95% CI 1.14–1.73, p=0.001]. Conclusion. Menopause and parity were associated with a curvier lumbar spine and osteoporosis with decreased vertebral height. Shape was not associated with back pain. No conflicts of interest.  . Sources of funding. Wellcome Trust collaborative award ref 209233

Background. Chronic back pain (CBP) is a major cause of disability globally and its causes are multifactorial. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are human herpes viruses usually acquired in early life. About 50% and over 90% of the population worldwide have been infected with CMV and EBV, respectively. This study investigated a potential causal relationship between CMV infection and CBP. Method. UK Biobank participants provided information on CMV seropositivity and CBP status, which were available for both traits in 5,140 participants. We used EBV seropositivity as a negative control to identify confounding and inaccurate causal inference. A one-sample Mendelian randomization (MR) based on independent genetic variants predicting CMV and EBV positivity was conducted in Northern European participants. To validate the association further, the MR study was repeated using a CMV polygenic risk score (PRS). Results. CMV GWAS revealed 86 independent SNPs having p-value < 2 × 10. −4. for the one-sample MR. These SNPs were used to define genetically-predicted categories of CMV infection risk. CMV infection risk categories were significantly associated with CBP (OR = 1.150; 95% CI: 1.005–1.317, p-value = 0.043), findings which were confirmed using the CMV PRS (OR = 1.299; 95% CI: 1.141–1.479, p-value = 0.001). There was no causal association between EBV and CBP (p-value = 0.17). Conclusion. Our results provide further evidence for a causal relationship between CMV infection and CBP. These results suggest a stratified approach to CBP may be useful, particularly in clinical trials and they shed light on underlying mechanisms in CBP. Conflicts of interest. No conflicts of interest. Sources of funding. No funding obtained. Acknowledgement. UKBB data were obtained under the project #18219. Some aspects of this work have been previously presented at The Challenge of Chronic Pain: From Genomics to Therapy in UK and first 1st Danish International Conference on Personalised Medicine in Denmark

Purpose of study and background. Spinal muscle area (SMA) is often employed to assess muscle functionality and is important for understanding the risk individuals may have of developing back pain or the risk of postural instability and falls.. However, handgrip strength (HGS) has also been utilized as a measure of general muscle capacity. This study aimed to examine the relationship between SMA and HGS to assess whether the latter could be used as an accurate indicator of the former. Methods. 150 participants (75 males and 75 females, aged 47–70 years) were selected from the UK Biobank dataset. Handgrip strength values were extracted and averaged over left and right values. Abdominal MRI images were examined and cross-sectional area of the erector spinae and multifidus determined at the L3/4 level and summed to provide a total muscle area. Results. HGS and SMA (mean±sd) were 39.6 ± 7.4 kg and 4664 ± 868 mm. 2. for males and 24.7 ± 5.9 kg, and 3822 ± 579 mm. 2. for females. Pearson correlation between HGS and SMA was r = 0.41 for males (p = <0.001), r = 0.40 for females (p = <0.001), and r = 0.61 for the combined groups (p<0.001). Conclusion. Significant correlations were found between HGS and SMA for individual sexes and combined groups. However, although HGS may be a useful measure for predicting modifications in group responses in spinal muscle function, for example, following an intervention, it does not have the power to confidently predict muscle values at an individual participant level. Conflicts of interest: No conflicts of interest. Sources of funding: Prince Sattam University, KSA, provided a PhD scholarship for Salman Alharthi

Aims

Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive.

Aims

Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease.