Assessing the genetic relationships between osteoarthritis and human plasma proteins: a large scale genetic correlation scan.

backgroundOsteoarthritis (OA) is a multifactorial complex disease. The impact of plasma proteins on OA remains elusive now.

methodsThe UK Biobank genome-wide association study data of OA was used here. Genome-wide SNP genotyping was performed using the Affymetrix UK BiLEVE Axiom or UK Biobank Axiom array. Equally, the GWAS summary data of 3,622 plasma proteins was derived from a recently published study. Consequently, linkage disequilibrium score regression (LD score regression) analysis was performed to evaluate the genetic correlation between each plasma protein and different sites of OA.

resultsSeveral suggestive plasma proteins were identified for OA. For hand OA, evidence of genetic correlation was observed for inter-alpha-trypsin inhibitor heavy chain H1 (coefficient =-0.3854, P value =0.0198), multiple inositol polyphosphate phosphatase 1 (coefficient =-1.1721, P value =0.0303). For hip OA, 7 suggestive genetic correlation signals were observed, such as Transmembrane glycoprotein NMB (coefficient =0.6944, P value =0.0098), Endothelial cell-specific molecule 1 (coefficient =0.6337, P value =0.03). For Knee OA, 12 suggestive genetic correlation signals were identified, including Elafin (coefficient =-0.5562, P value =0.0092), Interleukin-16 (coefficient =0.3949, P value =0.0435).

conclusionsWe investigated the genetic correlations between plasma proteins and different sites of OA in a systematic way. Our results provide novel evidence that OA is a heterogeneous disease.