Genetic association analysis: a primer on how it works, its strengths and its weaknesses

Summary Currently, the most used approach to mapping disease genes is the genome wide association study, using large samples of cases and controls and hundreds of thousands of markers spread throughout the genome. This review focuses in explaining how an association study works, its strengths and its weaknesses, and the methods available to analyse the data. Issues related to sample size, genetic effect sizes, epistasis, replication and population stratification are specifically addressed, issues that an investigator must take into account when planning an association study of any complex disease. Finally, we include some special features concerning association studies in the Y chromosome, and we contrast the analysis characteristics of linkage and association.