O11 - Is the risk of revision after arthroplasty surgery genetically determined? A genome-wide association study of single nucleotide polymorphisms in 1,130 arthroplasty-treated twins.

Hip
Anders Brüggemann1 , Niclas Eriksson2, Nancy L. Pedersen3, Karl Michaëlsson1, Nils P. Hailer1
1 Department of Surgical Sciences, Orthopaedics, Uppsala University, Uppsala, Sweden
2 Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
3 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Introduction: Ample evidence derived from candidate-gene approaches indicates that certain genes are associated with an increased risk of revision surgery following arthroplasty surgery. We aimed to identify genetic risk loci within the setting of a genome-wide association study (GWAS).
Patients and Methods: Genetic information on 1,130 individuals treated with arthroplasty surgery in the hip or knee joint was extracted from the Swedish Twin Registry’s TwinGene dataset. 94 of these underwent revision surgery. We conducted a GWAS using the Illumina OmniExpress and the Illumina Psych array. The Haplotype Reference Consortium served as the reference for data imputation. Since members of our cohort were siblings, Cox regression models with a robust sandwich estimator were fitted to identify single nucleotide polymorphisms (SNP) that were associated with the occurrence of revision surgery at a significance level of p<5*10-8.
Results: 4 statistically significant SNP that were all located on chromosome 3 in the SLC6A6 (sodium-dependent taurine and beta-alanine transporter) gene region reached statistical significance, with the leading SNP rs62233562 having a hazard ratio of 3.2 (95% CI 2.2-4.6, p=1.01*10-9). 27 SNP on chromosome 9 coding for the AB0-system were close to the level of statistical significance (range of p-values: 7.9*10-8 - 2.8*10-7).
Conclusions: We identified previously unknown genetic risk loci associated with the risk of revision surgery. The known close relationship of the SLC6A6 gene with trunk fat mass could guide future, candidate-driven studies in order to elucidate causal relationships. The potential influence of blood group factors on the risk of revision is an interesting finding that merits further investigation.