Grupo de Medicina Xenómica, Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
CIBERER-Instituto de Salud Carlos III, Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
J Clin Periodontol. 2021 Jul;48(7):896-906. doi: 10.1111/jcpe.13460. Epub 2021 Apr 19.
To identify loci associated with stages III/IV, grade C periodontitis (PIII/IV-C) through a genome-wide association study (GWAS).
441 Caucasian Spanish PIII/IV-C cases from the SEPA Network of Research Clinics and 1141 controls from the Banco Nacional de ADN were genotyped with "Axiom Spain Biobank Array," which contains 757836 markers, including rare and low-frequency Spanish variants. The analysis of the individual association and subsequently the gene-level analysis with Sequence Kernel Association Test (SKAT) were carried out adjusting for age, sex and PC1 covariates. Pathway Analysis was additionally performed with Ingenuity Pathway Analysis (IPA) software on the top associated genes.
In the individual analyses, no genome-wide significant signals were detected. However, 8 SNPs of 8 loci reached suggestive evidence of association with PIII/IV-C, including FAT3 rs35709256, CSNK1G2 rs4807188, MYH13 rs2074872, CNTN2 rs116611488, ANTXR1 rs4854545, 8p23.2 rs78672540, ANGPT1 rs13439823 and PLEC rs11993287 (p < 5 × 10 ). SKAT analysis identified other interesting signals at CNTN2, FBXO44, AP1M2, RSPO4, KRI1, BPIFB1 and INMT, although their probability does not exceed the multiple-test correction. IPA indicated significant enrichment of pathways related to cAMP, IL-2, CD28, VDR/RXR and PI3K/Akt. CONCLUSIONS: GWAS found no SNPs significantly associated with PIII/IV-C.
通过全基因组关联研究（GWAS）鉴定与 III/IV 期、C 级牙周炎（PIII/IV-C）相关的基因座。
来自 SEPA 研究诊所网络的 441 名西班牙白种人 PIII/IV-C 病例和来自 Banco Nacional de ADN 的 1141 名对照者，使用包含 757836 个标记物的“Axiom Spain Biobank Array”进行基因分型，包括罕见和低频的西班牙变体。对个体关联进行分析，然后使用序列核关联测试（SKAT）进行基因水平分析，调整年龄、性别和 PC1 协变量。在顶部相关基因上，使用 IPA 软件进行通路分析。
在个体分析中，没有检测到全基因组显著信号。然而，在 PIII/IV-C 中，有 8 个基因座的 8 个 SNP 达到了提示性关联的证据，包括 FAT3 rs35709256、CSNK1G2 rs4807188、MYH13 rs2074872、CNTN2 rs116611488、ANTXR1 rs4854545、8p23.2 rs78672540、ANGPT1 rs13439823 和 PLEC rs11993287（p<5×10）。SKAT 分析在 CNTN2、FBXO44、AP1M2、RSPO4、KRI1、BPIFB1 和 INMT 中发现了其他有趣的信号，尽管它们的概率没有超过多重测试校正。IPA 表明与 cAMP、IL-2、CD28、VDR/RXR 和 PI3K/Akt 相关的途径显著富集。
GWAS 未发现与 PIII/IV-C 显著相关的 SNP。
