Designing candidate gene and genome-wide case-control association studies

摘要

This protocol describes how to appropriately design a genetic association case-control study, either focussing on a candidate gene or region, or implementing a genome-wide approach. The steps described involve: 1) defining the case phenotype in adequate detail; 2) checking the heritability of the disease in question; 3) considering whether a population-based study is the appropriate design for the research question; 4) the appropriate selection of controls; 5) sample size calculations; and 6) giving due consideration to whether it is a de-novo or replication study. General guidelines are given, as well as specific examples of a candidate gene and a genome-wide association study into Type 2 Diabetes. Software and websites used in this protocol include the International HapMap Consortium website, Genetic Power Calculator, CaTS, and SNPSpD. Running each of the programmes only takes a few seconds; the rate-limiting steps involve thinking through the designs and parameters in the disease models.