A multi-trait approach identified 7 novel genes for back pain.

Introduction: Back pain (BP) is a complex heritable trait with an estimated heritability of 40% to 60%. Less than half of this can be explained by known genetic variants identified in genome-wide association studies.

Objectives: We applied a powerful multi-trait and gene-based approach to association analysis of BP to identify novel genes associated with BP.

A Mendelian randomization study finds no evidence for causal effects of C-reactive protein (CRP) on chronic pain conditions.

This two-sample Mendelian randomization study examined causal associations of C-reactive protein (CRP) with spinal pain, the extent of multisite chronic pain, and chronic widespread musculoskeletal pain. No causal associations were found between CRP and these pain conditions.

Quantitative sensory testing and chronic pain syndromes: a cross-sectional study from TwinsUK.

Objective: The chronic pain syndromes (CPS) include syndromes such as chronic widespread pain (CWP), dry eye disease (DED) and irritable bowel syndrome (IBS). Highly prevalent and lacking pathognomonic biomarkers, the CPS are known to cluster in individuals in part due to their genetic overlap, but patient diagnosis can be difficult. The success of quantitative sensory testing (QST) and inflammatory biomarkers as phenotyping tools in conditions such as painful neuropathies warrant their investigation in CPS.

No evidence for causal effects of C-reactive protein (CRP) on chronic pain conditions: a Mendelian randomization study.

Objective: We conducted a Mendelian randomization (MR) study to examine causal associations of C-reactive protein (CRP) with (1) spinal pain; (2) extent of multisite chronic pain; and (3) chronic widespread musculoskeletal pain.

Design: Two-sample MR study.

Setting/subjects: We used summary statistics from publicly available genome-wide association studies (GWAS) conducted in multiple cohorts and biobanks.

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.

Glycoprotein Acetyls Is a Novel Biomarker Predicting Cardiovascular Complications in Rheumatoid Arthritis.

The relationship between rheumatoid arthritis (RA) and early onset atherosclerosis is well depicted, each with an important inflammatory component. Glycoprotein acetyls (GlycA), a novel biomarker of inflammation, may play a role in the manifestation of these two inflammatory conditions. The present study examined a potential mediating role of GlycA within the RA-atherosclerosis relationship to determine whether it accounts for the excess risk of cardiovascular disease over that posed by lipid risk factors.

GlycA and CRP Are Genetically Correlated: Insight into the Genetic Architecture of Inflammageing.

Inflammageing is a condition of perpetual low-grade inflammation induced by ageing. Inflammageing may be predicted by the C-reactive protein (CRP) or by a recently described biomarker which measures N-glycosylated side chains of the carbohydrate component of several acute-phase proteins known as GlycA. The objective of this study was to examine in depth the genetic relationships between CRP and GlycA as well as between each of them and other selected cytokines, which may shed light on the mechanisms of inflammageing.

No evidence of association between either Modic change or disc degeneration and five circulating inflammatory proteins.

Introduction: Intervertebral disc degeneration and Modic change are the main spinal structural changes associated with chronic low back pain (LBP). Both conditions are thought to manifest local inflammation and if inflammatory proteins translocate to the blood circulation could be detected systemically. The work here assesses whether the presence of disc degeneration is associated with detectable blood level changes of five inflammatory markers and whether chronic LBP is associated with these changes.

Assessment of blood-brain barrier leakage and brain oxygenation in Connexin-32 knockout mice with systemic neuroinflammation using pulse electron paramagnetic resonance imaging techniques.

Purpose: The determination of blood-brain barrier (BBB) integrity and partial pressure of oxygen (pO) in the brain is of substantial interest in several neurological applications. This study aimed to assess the feasibility of using trityl OX071-based pulse electron paramagnetic resonance imaging (pEPRI) to provide a quantitative estimate of BBB integrity and pO maps in mouse brains as a function of neuroinflammatory disease progression.

Methods: Five Connexin-32 (Cx32)-knockout (KO) mice were injected with lipopolysaccharide to induce neuroinflammation for imaging.

Multi-Trait Exome-Wide Association Study of Back Pain-Related Phenotypes.

Back pain (BP) is a major contributor to disability worldwide, with heritability estimated at 40-60%. However, less than half of the heritability is explained by common genetic variants identified by genome-wide association studies. More powerful methods and rare and ultra-rare variant analysis may offer additional insight.

Repurposing Antihypertensive and Statin Medications for Spinal Pain: A Mendelian Randomization Study.

Study Design: Mendelian randomization (MR) study.

Objective: To examine whether antihypertensive medications (beta-blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors) and statins can be repurposed to prevent or treat spinal pain (back or neck pain).

Summary Of Background Data: Observational studies and a recent MR study have found associations between elevated blood pressure and a greater risk of back pain.

Development and Replication of a Genome-Wide Polygenic Risk Score for Chronic Back Pain.

Chronic back pain (CBP) is a complex heritable trait and a major cause of disability worldwide. We developed and validated a genome-wide polygenic risk score (PRS) for CBP using a large-scale GWAS based on UK Biobank participants of European ancestry (N = 265,000). The PRS showed poor overall predictive ability (AUC = 0.

Association between Gene Variants and Ischemic Stroke: A Pilot Study Providing Additional Evidence for the Role of Heat Shock Proteins in Disease Pathogenesis.

HSPA8 is involved in many stroke-associated cellular processes, playing a pivotal role in the protein quality control system. Here we report the results of the pilot study aimed at determining whether SNPs are linked to the risk of ischemic stroke (IS). DNA samples from 2139 Russians (888 IS patients and 1251 healthy controls) were genotyped for tagSNPs (rs1461496, rs10892958, and rs1136141) in the gene using probe-based PCR.

Apoptosis Genes as a Key to Identification of Inverse Comorbidity of Huntington's Disease and Cancer.

Cancer and neurodegenerative disorders present overwhelming challenges for healthcare worldwide. Epidemiological studies showed a decrease in cancer rates in patients with neurodegenerative disorders, including the Huntington disease (HD). Apoptosis is one of the most important processes for both cancer and neurodegeneration.

Polymorphism of , the gene encoding a heat-resistant obscure (Hero) protein with chaperone activity, is a novel link in ischemic stroke.

Background: Ischemic stroke (IS) is one of the most serious cardiovascular events associated with high risk of death or disability. The growing body of evidence highlights molecular chaperones as especially important players in the pathogenesis of the disease. Since six small proteins called "Hero" have been recently identified as a novel class of chaperones we aimed to evaluate whether SNP rs4644832 in gene encoding the member of Hero-proteins, is associated with the risk of IS.

SERPINE1 mRNA Binding Protein 1 Is Associated with Ischemic Stroke Risk: A Comprehensive Molecular-Genetic and Bioinformatics Analysis of SNPs.

The gene is a well-known regulator of SERPINE1 mRNA stability and progesterone signaling. However, the chaperone-like properties of have recently been discovered. The present pilot study investigated whether SNPs are associated with the risk and clinical manifestations of ischemic stroke (IS).

Genotype-by-environment interactions in chronic back pain.

Background Context: Chronic back pain (CBP) is a common debilitating condition with substantial societal impact. While understanding genotype-by-environment (GxE) interactions may be crucial to achieving the goals of personalized medicine, there are few large-scale studies investigating this topic for CBP. None of them systematically explore multiple CBP risk factors.

Evidence of causal effects of blood pressure on back pain and back pain on type II diabetes provided by a bidirectional Mendelian randomization study.

Background Context: Cardiovascular risk factors (hypertension, dyslipidemia, and type II diabetes) have been proposed as risk factors for back pain. However, few longitudinal studies have found significant associations between cardiovascular risk factors and back pain, and these may be explained by confounding or reverse causation.

Purpose: To examine potential causal effects of cardiovascular risk factors on back pain, and vice versa.

Ficolin-3 and MASP-2 gene variants in Siberian arctic populations: Summarized evidence of selective pressure for the high frequency of lectin complement pathway deficiency.

Herewith, we provide novel original data about the prevalence of FCN3 rs532781899 and MASP2 rs72550870 variants among the newborns of aboriginal Siberian Arctic populations (Nenets and Dolgan-Nganasans) and Russians of East Siberia. This novel data has been analysed along with the genetic data about other proteins of the lectin pathway of the complement system (mannose-binding lectin and ficolin-2) obtained earlier. A total of 926 specimens of dried blood spots of the newborns were genotyped.