Genome-wide association studies--a summary for the clinical gastroenterologist.
Genome-wide association studies (GWAS) have been applied to various gastrointestinal and liver diseases in recent years. A large number of susceptibility genes and key biological pathways in disease development have been identified. So far, studies in inflammatory bowel diseases, and in particular Crohn's disease, have been especially successful in defining new susceptibility loci using the GWAS design. The identification of associations related to autophagy as well as several genes involved in immunological response will be important to future research on Crohn's disease. In this review, key methodological aspects of GWAS, the importance of proper cohort collection, genotyping issues and statistical methods are summarized. Ways of addressing the shortcomings of the GWAS design, when it comes to rare variants, are also discussed. For each of the relevant conditions, findings from the various GWAS are summarized with a focus on the affected biological systems.
Melum
Espen
E
Medical Department, Rikshospitalet, Oslo University Hospital, N-0027 Oslo, Norway.
Franke
Andre
A
Karlsen
Tom H
TH
D003424:Crohn Disease / Q000235:genetics; D005762:Gastroenterology / Q000379:methods*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D017720:Molecular Epidemiology / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D012107:Research Design; D012306:Risk