Figure 2.
Schematic workflow of the study design of the human association analysis. (1) Hypothesis-generating step: all single-nucleotide polymorphisms (SNPs) within 200 kb up- and downstream of the candidate genes were tested for association with aggressive periodontitis (AgP), the most severe phenotype (PF4/PPBP/CXCL5: 1,130 SNPs; STOML3: 2,098 SNPs; UGT2A1-SULT1D1P: 363 SNPs). SNPs with an association of P < 10−3 (additive model) were located at PF4/PPBP/CXCL5 and UGT2A1. (2) The most significant tagging SNPs of each of the 2 AgP-associated haplotype blocks at PF4/PPBP/CXCL5 and UGT2A1 were selected for validation in a large sample of the moderate phenotype chronic periodontitis (CP). The association of rs1595009 at PF4/PPBP/CXCL5 was nominally significant (additive model), but not rs146712414 at UGT2A1. (3) rs1595009 was selected for replication in an independent case-control sample of CP and showed nominal significant association at the recessive model. (After increasing the size of the control sample by adding the German AgP controls, the association was also nominally significant at the additive model; see the main text.)