Case-Control Designs for Modern Genome-Wide Association Studies: Basic Principles and Overview

Genetic linkage studies of highly affected families have long been used to identify genomic regions that harbor rare high penetrant mutations for various diseases and conditions (Botstein and Risch, 2003); gusella1983polymorphic; hall1990linkage; kerem1989identification; nishisho1991mutations. The completion of the Human Genome Sequencing project (International Human Genome Sequencing Consortium, 2001) in the beginning of this century and subsequent development of cost-effective large-scale genotyping and sequencing technologies ushered the era of genome-wide association studies (GWAS) in the last decade (Hirschhorn and Daly, 2005); mccarthy2008genome; wang2005genome; wellcome2007genome.