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Abstract：
We sought to replicate findings from published genome-wide association studies (GWAS), linking specific candidate gene loci with periodontitis-related clinical/microbial traits.
In the published GWAS, a total of 2196 single nucleotide polymorphisms associated with periodontitis-related traits at a p ≤ 5 × 10-6 and mapped to 136 gene loci. The replication cohort included 1124 individuals, 65-98 years old (67% female, 45% Hispanic, 30% Black, 23% White) with available genome-wide genotypes and full-mouth periodontal status. Microbial profiles using checkerboard DNA-DNA hybridization and 16SrRNA sequencing were available from 912 and 739 participants, respectively.
Using gene-specific p-values after linkage disequilibrium pruning, the following gene/phenotype associations replicated successfully: CLEC19A with edentulism and %teeth with pocket depth (PD) ≥4 mm; IL37, HPVC1, TRPS1, ABHD12B, LDLRAD4 (C180rF1), TGM3, and GRK5 with %teeth with PD ≥4 mm; DAB2IP with presence of PD ≥6 mm; KIAA1715(LNPK), ROBO2, RAB28, LINC01017, NELL1, LDLRAD4(C18orF1), and CRYBB2P1 with %teeth with clinical attachment level (CAL) ≥3 mm; RUNX2 and LAMA2 with %teeth with CAL ≥5 mm; and KIAA1715(LNPK) with high colonization by Aggregatibacter actinomycetemcomitans. In addition, CLEC19A, IQSEC1, and EMR1 associated with microbial abundance based on checkerboard data, LBP and NCR2 with abundance based on sequencing data, and NCR2 with microbial diversity based on sequencing data.
Several gene loci identified in published GWAS as associated with periodontitis-related phenotypes replicated successfully in an elderly cohort.
In the published GWAS, a total of 2196 single nucleotide polymorphisms associated with periodontitis-related traits at a p ≤ 5 × 10-6 and mapped to 136 gene loci. The replication cohort included 1124 individuals, 65-98 years old (67% female, 45% Hispanic, 30% Black, 23% White) with available genome-wide genotypes and full-mouth periodontal status. Microbial profiles using checkerboard DNA-DNA hybridization and 16SrRNA sequencing were available from 912 and 739 participants, respectively.
Using gene-specific p-values after linkage disequilibrium pruning, the following gene/phenotype associations replicated successfully: CLEC19A with edentulism and %teeth with pocket depth (PD) ≥4 mm; IL37, HPVC1, TRPS1, ABHD12B, LDLRAD4 (C180rF1), TGM3, and GRK5 with %teeth with PD ≥4 mm; DAB2IP with presence of PD ≥6 mm; KIAA1715(LNPK), ROBO2, RAB28, LINC01017, NELL1, LDLRAD4(C18orF1), and CRYBB2P1 with %teeth with clinical attachment level (CAL) ≥3 mm; RUNX2 and LAMA2 with %teeth with CAL ≥5 mm; and KIAA1715(LNPK) with high colonization by Aggregatibacter actinomycetemcomitans. In addition, CLEC19A, IQSEC1, and EMR1 associated with microbial abundance based on checkerboard data, LBP and NCR2 with abundance based on sequencing data, and NCR2 with microbial diversity based on sequencing data.
Several gene loci identified in published GWAS as associated with periodontitis-related phenotypes replicated successfully in an elderly cohort.
摘要：
我们试图复制已发表的全基因组关联研究（GWAS）的发现，将特定的候选基因位点与牙周炎相关的临床/微生物特征联系起来。
在已发布的GWAS中，在p≤5×10-6时，共有2196个与牙周炎相关性状相关的单核苷酸多态性，并定位到136个基因位点。复制队列包括1124个人，65-98岁（67%为女性，45%的西班牙裔,30%黑色,23％白色）具有可用的全基因组基因型和全口牙周状态。912名和739名参与者使用棋盘DNA-DNA杂交和16SrRNA测序获得了微生物谱，分别。
使用连锁不平衡修剪后的基因特异性p值，成功复制了以下基因/表型关联：CLEC19A伴牙瘤和百分比牙齿的口袋深度（PD）≥4mm；IL37，HPVC1，TRPS1，ABHD12B，LDLRAD4(C180rF1),TGM3和GRK5的齿%PD≥4mm;DAB2IPPD≥6mm;KIAA1715(LNPK),ROBO2,RAB28,LINC01017,NELL1,LDLRAD4(C18orF1),和CRYBB2P1，其临床附着水平（CAL）≥3mm的牙齿百分比；RUNX2和LAMA2，其CAL≥5mm的牙齿百分比；和KIAA1715（LNPK），其被放线菌放线菌高定植。此外,CLEC19A,IQSEC1和EMR1与基于棋盘数据的微生物丰度相关，基于测序数据的LBP和NCR2丰度，和基于测序数据的具有微生物多样性的NCR2。
在发表的GWAS中确定的与牙周炎相关表型相关的几个基因位点在老年队列中成功复制。
在已发布的GWAS中，在p≤5×10-6时，共有2196个与牙周炎相关性状相关的单核苷酸多态性，并定位到136个基因位点。复制队列包括1124个人，65-98岁（67%为女性，45%的西班牙裔,30%黑色,23％白色）具有可用的全基因组基因型和全口牙周状态。912名和739名参与者使用棋盘DNA-DNA杂交和16SrRNA测序获得了微生物谱，分别。
使用连锁不平衡修剪后的基因特异性p值，成功复制了以下基因/表型关联：CLEC19A伴牙瘤和百分比牙齿的口袋深度（PD）≥4mm；IL37，HPVC1，TRPS1，ABHD12B，LDLRAD4(C180rF1),TGM3和GRK5的齿%PD≥4mm;DAB2IPPD≥6mm;KIAA1715(LNPK),ROBO2,RAB28,LINC01017,NELL1,LDLRAD4(C18orF1),和CRYBB2P1，其临床附着水平（CAL）≥3mm的牙齿百分比；RUNX2和LAMA2，其CAL≥5mm的牙齿百分比；和KIAA1715（LNPK），其被放线菌放线菌高定植。此外,CLEC19A,IQSEC1和EMR1与基于棋盘数据的微生物丰度相关，基于测序数据的LBP和NCR2丰度，和基于测序数据的具有微生物多样性的NCR2。
在发表的GWAS中确定的与牙周炎相关表型相关的几个基因位点在老年队列中成功复制。
