A novel multi-locus genetic risk score identifies patients with higher risk of generalized aggressive periodontitis

Background Each genetic variant individually explains only a tiny proportion of the genetic variation with insignificant predictive power. The tool of multi-locus genetic risk score (GRS), which aggregates information from multiple genetic variants, has been widely used in many complex diseases but not yet applied to generalized aggressive periodontitis (GAgP). Methods A total of 335 GAgP patients and 114 healthy controls were enrolled in the case-control study. The unweighted GRS (uGRS) and weighted GRS (wGRS) were calculated based on significant variants. Logistic regression models were conducted for the GRS-based association analyses on the risk of GAgP. Receiver operating characteristic analysis was performed to compare the discriminatory ability of predictors of GAgP risk. Results Four loci were found to be significantly associated with GAgP. They were matrix metalloproteinase 8 rs11225395 (odds ratio [OR] = 1.40, 95% CI: 1.03 to 1.91), epidermal growth factor rs2237051 (OR = 1.41, 95% CI: 1.03 to 1.93), PPAR-a rs4253623 (OR = 1.53, 95% CI: 1.03 to 2.26), and apolipoprotein E rs429358 (OR = 1.79, 95% CI: 1.08 to 2.97). Each additional point of the uGRS/wGRS was associated with a 50%/31% increased risk of developing GAgP (OR = 1.50, 95% CI: 1.21 to 1.85 or OR = 1.31, 95% CI: 1.14 to 1.51, respectively) after adjusting for age, sex, and body mass index (BMI). Participants in the high group of uGRS/wGRS (OR = 2.87, 95% CI: 1.59 to 5.17 or OR = 2.67, 95% CI: 1.46 to 4.88, respectively) and the middle group of uGRS/wGRS (OR = 2.21, 95% CI: 1.29 to 3.78 or OR = 1.88, 95% CI: 1.09 to 3.08, respectively) had an increased risk of GAgP compared with those in the low group of score after adjustment for age, sex, and BMI. The addition of GRS to a model of conventional risk factors improved discrimination by 4.5% (from 0.695 to 0.740,P = 0.048). Conclusions We demonstrated that the multi-locus GRS based on four significant single nucleotide polymorphisms might be useful to assess genetic predisposition to GAgP. The GRS in combination with conventional risk factors significantly improved the power of identifying subgroups of Chinese population with a particularly high risk for GAgP.