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.

Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery.

The Open Targets Platform (https://platform.opentargets.org) is a unique, open-source, publicly-available knowledge base providing data and tooling for systematic drug target identification, annotation, and prioritisation.

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.

Genotype imputation in human genomic studies.

Imputation is a method that supplies missing information about genetic variants that could not be directly genotyped with DNA microarrays or low-coverage sequencing. Imputation plays a critical role in genome-wide association studies (GWAS). It leads to a significant increase in the number of studied variants, which improves the resolution of the method and enhances the comparability of data obtained in different cohorts and/or by using different technologies, which is important for conducting meta-analyses.

A New Method for Conditional Gene-Based Analysis Effectively Accounts for the Regional Polygenic Background.

Gene-based association analysis is a powerful tool for identifying genes that explain trait variability. An essential step of this analysis is a conditional analysis. It aims to eliminate the influence of SNPs outside the gene, which are in linkage disequilibrium with intragenic SNPs.

The BLUP method in evaluation of breeding values of Russian spring wheat lines using micro- and macroelements in seeds.

Genomic selection is a technology that allows for the determination of the genetic value of varieties of agricultural plants and animal breeds, based on information about genotypes and phenotypes. The measured breeding value (BV) for varieties and breeds in relation to the target trait allows breeding stages to be thoroughly planned and the parent forms suitable for crossing to be chosen. In this work, the BLUP method was used to assess the breeding value of 149 Russian varieties and introgression lines (4 measurements for each variety or line, 596 phenotypic points) of spring wheat according to the content of seven chemical elements in the grain - K, Ca, Mg, Mn, Fe, Zn, Cu.

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.

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.

Population Structure and Genetic Diversity of the 175 Soybean Breeding Lines and Varieties Cultivated in West Siberia and Other Regions of Russia.

Soybean is a leguminous plant cultivated in many countries and is considered important in the food industry due to the high levels of oil and protein content in the beans. The high demand for soybeans and its products in the industry requires the expansion of cultivation areas. Despite climatic restrictions, West Siberia is gradually expanding its area of soybean cultivation.

Multivariate Genome-Wide Association Study of Concentrations of Seven Elements in Seeds Reveals Four New Loci in Russian Wheat Lines.

Wheat is a cereal grain that plays an important role in the world's food industry. The identification of the loci that change the concentration of elements in wheat seeds is an important challenge nowadays especially for genomic selection and breeding of novel varieties. In this study, we performed a multivariate genome-wide association study (GWAS) of the seven traits-concentrations of Zn, Mg, Mn, Ca, Cu, Fe, and K in grain-of the Russian collection of common wheat (N = 149 measured in two years in two different fields).

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.

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.

Loci Associated with Negative Heterosis for Viability and Meat Productivity in Interspecific Sheep Hybrids.

Negative heterosis can occur on different economically important traits, but the exact biological mechanisms of this phenomenon are still unknown. The present study focuses on determining the genetic factors associated with negative heterosis in interspecific hybrids between domestic sheep () and argali (). One locus (rs417431015) associated with viability and two loci (rs413302370, rs402808951) associated with meat productivity were identified.

Noncoding rare variants in PANX3 are associated with chronic back pain.

Back pain is the leading cause of years lived with disability worldwide, yet surprisingly, little is known regarding the biology underlying this condition. The impact of genetics is known for chronic back pain: its heritability is estimated to be at least 40%. Large genome-wide association studies have shown that common variation may account for up to 35% of chronic back pain heritability; rare variants may explain a portion of the heritability not explained by common variants.

Method for the Isolation of "RNA-seq-Quality" RNA from Human Intervertebral Discs after Mortar and Pestle Homogenization.

The problem of isolating high-quality total RNA from intervertebral discs has no recognized solution yet. This is due to the extremely low content of live cells in the samples and the voluminous intercellular matrix. A variety of published protocols focused on isolating RNA from articular cartilage have recommended the use of expensive equipment, enzymatic matrix cleavage, or cell culture.

A Novel Framework for Analysis of the Shared Genetic Background of Correlated Traits.

We propose a novel effective framework for the analysis of the shared genetic background for a set of genetically correlated traits using SNP-level GWAS summary statistics. This framework called SHAHER is based on the construction of a linear combination of traits by maximizing the proportion of its genetic variance explained by the shared genetic factors. SHAHER requires only full GWAS summary statistics and matrices of genetic and phenotypic correlations between traits as inputs.

The GWAS-MAP|ovis platform for aggregation and analysis of genome-wide association study results in sheep.

In recent years, the number of genome-wide association studies (GWAS) carried out for various economically important animal traits has been increasing. GWAS discoveries provide summary statistics that can be used both for targeted marker-oriented selection and for studying the genetic control of economically important traits of farm animals. In contrast to research in human genetics, GWAS on farm animals often does not meet generally accepted standards (availability of information about effect and reference alleles, the size and direction of the effect, etc.

Causal effects of psychosocial factors on chronic back pain: a bidirectional Mendelian randomisation study.

Purpose: Risk factors for chronic back pain (CBP) may share underlying genetic factors, making them difficult to study using conventional methods. We conducted a bi-directional Mendelian randomisation (MR) study to examine the causal effects of risk factors (education, smoking, alcohol consumption, physical activity, sleep and depression) on CBP and the causal effect of CBP on the same risk factors.

Methods: Genetic instruments for risk factors and CBP were obtained from the largest published genome-wide association studies (GWAS) of risk factor traits conducted in individuals of European ancestry.

sumSTAAR: A flexible framework for gene-based association studies using GWAS summary statistics.

Gene-based association analysis is an effective gene-mapping tool. Many gene-based methods have been proposed recently. However, their power depends on the underlying genetic architecture, which is rarely known in complex traits, and so it is likely that a combination of such methods could serve as a universal approach.

Mendelian randomization analysis of plasma levels of CD209 and MICB proteins and the risk of varicose veins of lower extremities.

Varicose veins of lower extremities (VVs) are a highly prevalent condition, the pathogenesis of which is still not fully elucidated. Mendelian randomization (MR) can provide useful preliminary information on the traits that are potentially causally related to the disease. The aim of the present study is to replicate the effects of the plasma levels of MHC class I polypeptide-related sequence B (MICB) and cluster of differentiation 209 (CD209) proteins reported in a previous hypothesis-free MR study.

A protocol for recruiting and analyzing the disease-oriented Russian disc degeneration study (RuDDS) biobank for functional omics studies of lumbar disc degeneration.

Lumbar intervertebral disc degeneration (DD) disease is one of the main risk factors for low back pain and a leading cause of population absenteeism and disability worldwide. Despite a variety of biological studies, lumbar DD is not yet fully understood, partially because there are only few studies that use systematic and integrative approaches. This urges the need for studies that integrate different omics (including genomics and transcriptomics) measured on samples within a single cohort.