García-Closas Montserrat, Jacobs Kevin, Kraft Peter, Chatterjee Nilanjan
Institute of Cancer Research, Surrey, UK.
IARC Sci Publ. 2011(163):281-301.
This chapter describes basic principles in study design, data analysis, and interpretation of epidemiological studies of genetic polymorphisms and disease risk, including the assessment of gene-environment interactions. The case-control design (hospital-based, population-based or nested within a prospective cohort) is frequently used to study common genetic variants and disease risk. Because of their widespread use, the analysis of case-control data will be the focus of this chapter. Two key considerations in the study design will be addressed: the selection of genetic markers to be evaluated, and sample size considerations to ensure adequate power to detect associations with disease risk. Single nucleotide polymorphisms (SNPs) are the most frequent form of common genetic variation, thus the discussion on data analysis will be based on the evaluation of associations between SNPs and disease risk. This chapter will begin with the evaluation of quality control of genotyping data, which is a critical first step in the analysis of genetic data. A description of statistical methods will follow, aimed at the discovery of genetic susceptibility loci, including analysis of candidate SNPs and genome-wide association studies, haplotype analyses, and the evaluation of gene-gene and gene-environment interactions.
本章介绍了研究设计、数据分析以及基因多态性与疾病风险的流行病学研究解读的基本原则，包括基因 - 环境相互作用的评估。病例对照设计（基于医院、基于人群或嵌套在前瞻性队列中）常用于研究常见基因变异与疾病风险。由于其广泛应用，病例对照数据的分析将是本章的重点。将讨论研究设计中的两个关键考虑因素：待评估基因标记的选择以及样本量的考虑，以确保有足够的检验效能来检测与疾病风险的关联。单核苷酸多态性（SNP）是常见基因变异最常见的形式，因此关于数据分析的讨论将基于对SNP与疾病风险之间关联的评估。本章将首先评估基因分型数据的质量控制，这是遗传数据分析的关键第一步。随后将描述统计方法，旨在发现遗传易感性位点，包括候选SNP分析和全基因组关联研究、单倍型分析以及基因 - 基因和基因 - 环境相互作用的评估。
