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

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

Methods: The 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.

Results: Several 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).

Conclusions: We 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.