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