Protocols, Methods, and Tools for Genome-Wide Association Studies (GWAS) of Dental Traits
Protocols, Methods, and Tools for Genome-Wide Association Studies (GWAS) of Dental Traits
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DOI：
10.1007/978-1-4939-9012-2_38
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发表时间：
2019-01-01
期刊：
影响因子：
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通讯作者：
Divaris, Kimon
中科院分区：
文献类型：
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作者：
Agler, Cary S.;Shungin, Dmitry;Divaris, Kimon
众所周知，口腔健康和疾病受到环境(如社会和行为)因素和先天易感性之间复杂相互作用的影响。虽然基因组学和其他层次的“组学”对口腔健康的确切贡献是一个活跃的研究领域，但众所周知，对龋齿、牙周病和其他口腔和颅面特征的易感性在很大程度上受到人类基因组的影响。全面了解这些基因组因素对于实现口腔健康领域的精准医学是必要的。为了帮助这一方向，高通量基因分型的出现和负担能力的提高使得同时询问数百万个与口腔和颅面特征相关的基因多态成为可能。具体地说，对龋齿和牙周病的全基因组关联研究提供了对这两种常见的、复杂的、生物膜介导的疾病所涉及的新的基因座和生物学过程的初步见解。本文综述了牙龋病、牙周病及相关特征的GWA研究的方案、方法、工具和途径。该方案从考虑两种疾病的不同特征开始，概述了基因分型、质量控制、人口分层调整、遗传力和关联分析、注释、报告和解释的程序。可用于GWAS的方法和工具正在不断更新和改进；考虑到这一点，所提出的方法已成功地应用于许多GWAS和对数万人进行的荟萃分析，包括牙齿特征，如龋齿和牙周病。因此，它们可以作为未来对这些和其他特征的基因组研究的指南或模板。
Oral health and disease are known to be influenced by complex interactions between environmental (e.g., social and behavioral) factors and innate susceptibility. Although the exact contribution of genomics and other layers of "omics" to oral health is an area of active research, it is well established that the susceptibility to dental caries, periodontal disease, and other oral and craniofacial traits is substantially influenced by the human genome. A comprehensive understanding of these genomic factors is necessary for the realization of precision medicine in the oral health domain. To aid in this direction, the advent and increasing affordability of high-throughput genotyping has enabled the simultaneous interrogation of millions of genetic polymorphisms for association with oral and craniofacial traits. Specifically, genome-wide association studies (GWAS) of dental caries and periodontal disease have provided initial insights into novel loci and biological processes plausibly implicated in these two common, complex, biofilm-mediated diseases. This paper presents a summary of protocols, methods, tools, and pipelines for the conduct of GWAS of dental caries, periodontal disease, and related traits. The protocol begins with the consideration of different traits for both diseases and outlines procedures for genotyping, quality control, adjustment for population stratification, heritability and association analyses, annotation, reporting, and interpretation. Methods and tools available for GWAS are being constantly updated and improved; with this in mind, the presented approaches have been successfully applied in numerous GWAS and meta-analyses among tens of thousands of individuals, including dental traits such as dental caries and periodontal disease. As such, they can serve as a guide or template for future genomic investigations of these and other traits.