ArticleArthritis and rheumatism2010
Genome-wide linkage analysis of quantitative biomarker traits of osteoarthritis in a large, multigenerational extended family.
Article in Arthritis and rheumatism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- The viral and inflammation hypothesis of epileptic seizures based on bioinformatic study of circulating miRNAs and peripheral whole-blood mRNAs of adult epilepsy patients.Frontiers in neurology · 2022Article
- IGFBP7 acts as a negative regulator of RANKL-induced osteoclastogenesis and oestrogen deficiency-induced bone loss.Cell proliferation · 2020Article
- Serum N-propeptide of collagen IIA (PIIANP) as a marker of radiographic osteoarthritis burden.PloS one · 2017Article
- Genome-Wide DNA Methylation Study Identifies Significant Epigenomic Changes in Osteoarthritic Subchondral Bone and Similarity to Overlying Cartilage.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
- Republished: Value of biomarkers in osteoarthritis: current status and perspectives.Postgraduate medical journal · 2014Article
- TSG-6 activity as a novel biomarker of progression in knee osteoarthritis.Osteoarthritis and cartilage · 2014Article
- Value of biomarkers in osteoarthritis: current status and perspectives.Annals of the rheumatic diseases · 2013Review
- Personalized medicine for osteoarthritis: where are we now?Therapeutic advances in musculoskeletal disease · 2013Article
- Genome-wide linkage analysis of cardiovascular disease biomarkers in a large, multigenerational family.PloS one · 2013Article
- Shared genomic segment analysis: the power to find rare disease variants.Annals of human genetics · 2012Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveThe genetic contributions to the multifactorial disorder osteoarthritis (OA) have been increasingly recognized. The goal of the current study was to use OA-related biomarkers of severity and disease burden as quantitative traits to identify genetic susceptibility loci for OA.
methodsIn a large multigenerational extended family (n = 350), we measured 5 OA-related biomarkers: hyaluronan (HA), cartilage oligomeric matrix protein (COMP), N-propeptide of type IIA collagen (PIIANP), C-propeptide of type II procollagen (CPII), and type II collagen neoepitope (C2C). Single-nucleotide polymorphism markers (n = 6,090) covering the whole genome were genotyped using the Illumina HumanLinkage-12 BeadChip. Variance components analysis, as implemented in the Sequential Oligogenic Linkage Analysis Routines, was used to estimate heritabilities of the quantitative traits and to calculate 2-point and multipoint logarithm of odds (LOD) scores using a polygenic model.
resultsAfter adjusting for age and sex, we found that 4 of the 5 biomarkers exhibited significant heritability (PIIANP 0.57, HA 0.49, COMP 0.43, C2C 0.30; P < or = 0.01 for all). Fourteen of the 19 loci that had multipoint LOD scores of >1.5 were near to or overlapped with previously reported OA susceptibility loci. Four of these loci were identified by more than 1 biomarker. The maximum multipoint LOD scores for the heritable quantitative biomarker traits were 4.3 for PIIANP (chromosome 8p23.2), 3.2 for COMP (chromosome 8q11.1), 2.0 for HA (chromosome 6q16.3), and 2.0 for C2C (chromosome 5q31.2).
conclusionHerein, we report the first evidence of genetic susceptibility loci identified by OA-related biomarkers in an extended family. Our results demonstrate that serum concentrations of PIIANP, HA, COMP, and C2C have substantial heritable components, and using these biomarkers, several genetic loci potentially contributing to the genetic diversity of OA were identified.
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