Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions
Autor: | Jan Van Zundert, Elizaveta E Elgaeva, Pradeep Suri, Alexandra S. Shadrina, Yakov A. Tsepilov, Sodbo Zh Sharapov, Yurii S. Aulchenko, Frances M K Williams, Maxim B. Freidin, Lennart С Karssen |
---|---|
Přispěvatelé: | Anesthesiologie, MUMC+: CAKZ Pijnkennis Ane (9), MUMC+: MA Anesthesiologie (9), RS: MHeNs - R3 - Neuroscience |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Statistical methods Medicine (miscellaneous) Genome-wide association study Osteoarthritis VARIANTS Bioinformatics Genome-wide association studies 0302 clinical medicine Medicine GWAS Musculoskeletal Diseases Big Five personality traits lcsh:QH301-705.5 Principal Component Analysis Neck Pain Musculoskeletal system EXTRACELLULAR-MATRIX PROTEIN-1 GDF5 Genetic Pleiotropy Middle Aged DEPRESSION Phenotype Arthralgia PREVALENCE Female Chronic Pain General Agricultural and Biological Sciences hormones hormone substitutes and hormone antagonists Musculoskeletal pain EXPRESSION Adult Quantitative trait loci endocrine system SNP Locus (genetics) Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Shoulder Pain Genetic variation Humans METAANALYSIS Genetic Association Studies Aged business.industry Anthropometry medicine.disease OSTEOARTHRITIS SUSCEPTIBILITY 030104 developmental biology lcsh:Biology (General) Back Pain Genetic Loci business 030217 neurology & neurosurgery Genome-Wide Association Study |
Zdroj: | Communications Biology, Vol 3, Iss 1, Pp 1-13 (2020) Communications Biology Communications Biology, 3(1):329. Nature Publishing Group |
ISSN: | 2399-3642 |
Popis: | Chronic musculoskeletal pain affects all aspects of human life. However, mechanisms of its genetic control remain poorly understood. Genetic studies of pain are complicated by the high complexity and heterogeneity of pain phenotypes. Here, we apply principal component analysis to reduce phenotype heterogeneity of chronic musculoskeletal pain at four locations: the back, neck/shoulder, hip, and knee. Using matrices of genetic covariances, we constructed four genetically independent phenotypes (GIPs) with the leading GIP (GIP1) explaining 78.4% of the genetic variance of the analyzed conditions, and GIP2–4 explain progressively less. We identified and replicated five GIP1-associated loci and one GIP2-associated locus and prioritized the most likely causal genes. For GIP1, we showed enrichment with multiple nervous system-related terms and genetic correlations with anthropometric, sociodemographic, psychiatric/personality traits and osteoarthritis. We suggest that GIP1 represents a biopsychological component of chronic musculoskeletal pain, related to physiological and psychological aspects and reflecting pain perception and processing. Yakov Tsepilov, Maxim Freidin et al. find that chronic musculoskeletal pain conditions at four distinct anatomical sites share a common genetic background. The authors constructed genetically independent phenotypes (GIP) from principal components analysis of the different pain phenotypes and used the GIPs to perform genome-wide association studies to identify underlying genetic factors. |
Databáze: | OpenAIRE |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |