GENOME-WIDE ASSOCIATION STUDY OF PERIODONTAL DISEASE

牙周疾病全基因组关联研究

• 批准号: 8023292
• 负责人: Steven Offenbacher
• 金额: $ 33.2万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8023292
• 关键词: Adult; Atherosclerosis; Bacteria; Body Composition; Campylobacter rectus; Candidate Disease Gene; Chronic; Clinical; Collaborations; Communities; Data; Data Analyses; Data Set; Databases; Dental; Diabetes Mellitus; Diagnostic; Disease; Disease Resistance; Disease susceptibility; Dizygotic Twins; Epidemiologist; Generations; Genes; Genetic; Genome; Genomics; Genotype; Germany; Gingivitis; Goals; Haplotypes; Health; Heritability; Human; Immune response; Individual; Inflammatory Response; Lead; Medical; Medicine; Meta-Analysis; Metabolic; Microbe; Microbial Biofilms; Modeling; Modification; Monozygotic Twinning; Monozygotic twins; Mouth Diseases; Obesity; Organism; Patients; Pattern; Periodontal Diseases; Periodontitis; Phenotype; Population; Population Database; Population Study; Porphyromonas gingivalis; Predisposition; Protocols documentation; Public Health Schools; Race; Research Personnel; Resistance; Risk; Risk Assessment; Risk Factors; Role; School Dentistry; Severities; Smoking; Study Subject; Surveys; Validation; Variant; Work; case control; clinical phenotype; clinically relevant; community health study; disease classification; disease phenotype; edentulism; gene environment interaction; genetic association; genome wide association study; genome-wide; genome-wide analysis; meetings; microbial; novel; subgingival biofilm; therapeutic target

DESCRIPTION (provided by applicant): This application represents an exciting GWAS (Genome-Wide Association Study) to identify genes associated with edentulism, gingivitis and periodontitis. We intend to perform a GWAS meta-analysis using two primary databases; one with 6,786 subjects [from the Dental- Atherosclerosis Risk in Communities (DARIC) Study] and another with 4,308 subjects [from the Study of Health in Pomerania (SHIP) Study]. Both datasets have whole genomic genotyping data recently created using the Affymetrix Human SNP Array 6.0 and have detailed clinical periodontal examination data, and complete medical and risk factor data. We intend to use a meta-analysis approach combining these two datasets to identify genes that confer risk for edentulism, gingivitis and periodontitis. A third dataset of 3075 subjects [Health and Body Composition (HealthABC) Study] with periodontal phenotypes and genotype data created using the Illumina 1m SNP chip platform will be used for replication of these findings. This represents a collaboration that brings together the dental researchers at the UNC School of Dentistry using the Dental ARIC data, and the genetic epidemiologists at the UNC School of Public Health (DARIC) and two other groups - U of Greifswald Germany (SHIP) and UCLA/U of Pittsburgh (HealthABC). Together, we propose to perform what to our knowledge will be the first genome-wide survey for genes which are associated with periodontal disease in a representative adult population. We are fortunate to work with an outstanding genetic epidemiologist, Dr Kari North who will lead the genetic survey and statistical analyses. We have an approved ARIC protocol to analyze these data for gene associations for periodontal disease and have a commitment for the sharing of the SHIP and HealthABC datasets for the met-analysis and replication. We intend to conduct a GWAS applying various clinical case definitions of periodontal disease using existing data from both D-ARIC (n=6786) and SHIP (n=4,308). We propose to develop race-specific models for gene-wide associations using various definitions of oral disease - either categorical classifications of disease using clinically relevant clusters of clinical signs to define case status or by defining clinical phenotypes using clinical signs independently as continuous variables, such as mean interproximal attachment loss. We propose to analyze the two datasets independently and then conduct a meta-analysis pooling them, using harmonized variable definitions for the phenotypes. We also intend to examine for gene-environment interactions focusing on smoking, obesity, diabetes and microbial burden as effect modifiers. Finally, we will perform a replication analysis using the HealthABC dataset. Our goal is to identifying novel genes that confer either susceptibility or resistance to periodontal disease to enable us to usher in a new generation of periodontal diagnostics, risk assessments and enable targeted therapeutics; as a realization of personalized medicine. PUBLIC HEALTH RELEVANCE: This application seeks to conduct a genome-wide association study (GWAS) to identify candidate genes that are associated with edentulism, gingivitis and periodontal disease using two representative community dwelling populations of approximately 11,084 individuals. This project seeks to perform a GWAS meta-analysis on this population that has full genotyping, clinical phenotyping medical and risk factor data, and replicating the findings using a third database of over 1000 subjects. This is a unique opportunity to perform the first GWAS on periodontal disease in representative community populations with a range of disease, and to conduct gene-environment interaction analyses using microbial load, metabolic status (diabetes and obesity) and smoking as exposures. Our goal is to identify new genes that confer susceptibility and resistance to periodontal disease to enable us to usher in a new era of periodontal diagnostics, risk assessment and targeted therapy.

描述（由申请人提供）：此申请代表了一项令人兴奋的GWA（全基因组关联研究），以鉴定与义务，牙龈炎和牙周炎相关的基因。我们打算使用两个主要数据库进行GWAS荟萃分析。一个患有6,786名受试者（来自社区的牙科动脉粥样硬化风险（DARIC）研究），另一名受试者有4,308名受试者[来自波美尼亚健康研究（Ship）研究]。这两个数据集都有最近使用Affymetrix Human SNP阵列6.0创建的全基因组基因分型数据，并具有详细的临床牙周检查数据，并完整的医疗和风险因素数据。我们打算使用将这两个数据集结合起来的荟萃分析方法来识别赋予e牙，牙龈炎和牙周炎风险的基因。使用Illumina 1M 1M SNP芯片平台创建的牙周表型和基因型数据的3075名受试者[健康和身体组成（HealthABC）研究]的第三个数据集将用于复制这些发现。这代表了一种合作，该合作使用牙科牙科学院的牙科研究人员使用牙科研究人员，以及UNC公共卫生学院（DARIC）的遗传流行病学家（DARIC）以及其他两个组-Greifswald德国U的UCLA（Ship）和UCLA/UCLA/UCLA/UCLA/UCLA/UCH/UCH/U pittsburgh（HealthAbc）。我们共同提议对我们所知的事情进行，这将是针对代表性成年人口中与牙周疾病有关的基因的首次基因组调查。我们很幸运能与一位出色的遗传流行病学家Kari North博士合作，他将领导遗传调查和统计分析。我们拥有批准的ARIC方案，可以分析这些数据的基因关联，以进行牙周疾病，并承诺共享船舶和HealthABC数据集以进行荟萃分析和复制。我们打算使用来自D-Aric（n = 6786）和船舶（n = 4,308）的现有数据，使用各种牙周疾病的临床病例定义进行GWA。我们建议使用口腔疾病的各种定义开发种族特异性模型，以使用临床相关的临床体征簇进行疾病的各种定义，以定义病例状态，或通过使用临床表症来定义临床表型，将临床表征独立作为连续变量，例如平均插入式插入式植入术。我们建议独立分析两个数据集，然后使用对表型的统一变量定义进行汇总分析。我们还打算研究以吸烟，肥胖，糖尿病和微生物负担为效应修饰的基因环境相互作用。最后，我们将使用HealthABC数据集执行复制分析。我们的目标是确定具有对牙周疾病敏感性或抗性的新基因，以使我们能够迎来新一代的牙周诊断，风险评估并实现靶向治疗剂；作为个性化医学的实现。 公共卫生相关性：该应用程序旨在进行全基因组协会研究（GWAS），以使用大约11,084个人的两个代表性社区住宅种群来识别与依术，牙龈炎和牙周疾病相关的候选基因。该项目旨在对具有完整基因分型，临床表型医学和危险因素数据的该人群进行GWAS荟萃分析，并使用第三个超过1000名受试者的数据库复制发现。这是一个独特的机会，可以在具有多种疾病的代表性社区人群中对牙周疾病进行第一个GWA，并使用微生物负荷，代谢状态（糖尿病和肥胖症）和吸烟作为暴露进行基因环境相互作用分析。我们的目标是确定具有赋予牙周疾病敏感性和抵抗力的新基因，使我们能够进入牙周诊断，风险评估和靶向治疗的新时代。