Publications by authors named "Guillaume Aubourg"
Background: Transitioning from a genetic association signal to an effector gene and a targetable molecular mechanism requires the application of functional fine-mapping tools such as reporter assays and genome editing. In this report, we undertook such studies on the osteoarthritis (OA) risk that is marked by single nucleotide polymorphism (SNP) rs34195470 (A > G). The OA risk-conferring G allele of this SNP associates with increased DNA methylation (DNAm) at two CpG dinucleotides within WWP2.
View Article and Find Full Text PDFBackground: Osteoarthritis is highly heritable and genome-wide studies have identified single nucleotide polymorphisms (SNPs) associated with the disease. One such locus is marked by SNP rs11732213 (T > C). Genotype at rs11732213 correlates with the methylation levels of nearby CpG dinucleotides (CpGs), forming a methylation quantitative trait locus (mQTL).
View Article and Find Full Text PDFObjective: To identify methylation quantitative trait loci (mQTLs) correlating with osteoarthritis (OA) risk alleles and to undertake mechanistic characterization as a means of target gene prioritization.
Methods: We used genome-wide genotyping and cartilage DNA methylation array data in a discovery screen of novel OA risk loci. This was followed by methylation, gene expression analysis, and genotyping studies in additional cartilage samples, accompanied by in silico analyses.
Article Synopsis
- Osteoarthritis (OA) is a common joint disease that can lead to severe pain and the need for joint replacement surgery, affecting mobility.
- Research on tissue samples from 260 OA patients combined with experiments like CRISPR-Cas9 identified an important regulatory element linked to OA risk, particularly highlighting changes in DNA methylation that influence gene expression.
- The key findings show that the RUNX2 gene, essential for joint health, is significantly impacted by specific SNPs associated with OA risk, suggesting that genetic and epigenetic factors work together to affect joint function.
Article Synopsis
- Osteoarthritis (OA) is a painful joint disease caused by age-related cartilage loss, and genetic studies have pinpointed several DNA polymorphisms linked to OA risk.
- Researchers examined the link between these genetic variations and DNA methylation patterns in cartilage samples to see if they act as methylation quantitative trait loci (meQTLs).
- They found four significant meQTLs associated with OA susceptibility, which were confirmed in an additional patient group, enhancing the understanding of how genetics and epigenetics contribute to OA.