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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 utilized in many complex diseases but not applied to generalized aggressive periodontitis (GAgP) yet.


OBJECTIVE
To examine the joint genetic effects of significant risk variants based on a candidate gene study and their combination effects with conventional risk factors on risk of GAgP.


METHODS
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 (ROC) 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 MMP8 rs11225395 (OR = 1.40, 95%CI: 1.03, 1.91), EGF rs2237051 (OR = 1.41, 95%CI: 1.03, 1.93), PPAR-a rs4253623 (OR = 1.53, 95%CI: 1.03, 2.26) and APOE rs429358 (OR = 1.79, 95%CI: 1.08, 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: 1.21-1.85 or OR = 1.31, 95% CI: 1.14-1.51, respectively) after adjusting for age, gender and BMI. Participants in the high group of uGRS/wGRS (OR = 2.87, 95%CI: 1.59-5.17 or OR = 2.67, 95%CI: 1.46-4.88, respectively) and the middle group of uGRS/wGRS (OR = 2.21, 95%CI: 1.29-3.78 or OR = 1.88, 95%CI: 1.09-3.08, respectively) had an increased risk of GAgP comparing with those in the low group of score after adjustment for age, gender 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).


CONCLUSION
We demonstrated that the multi-locus GRS based on 4 significant SNPs might be useful for assessing 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. This article is protected by copyright. All rights reserved.