Genome-Wide Association Studies
Genome-wide association (GWA) studies are best understood as an extension of candidate gene association studies, scaled up to cover hundreds of thousands of markers across the genome in samples usually of several thousand cases and controls. The GWA approach allows the detection of much smaller effect sizes than with previous linkage-based genome-wide studies. However, this sensitivity makes them vulnerable to false positive findings caused by subtle differences between cases and controls that may arise as a result of issues, such as genotyping errors, population stratification, and sample mix-ups as well as the more obvious issue of multiple testing. After some background and an introduction to GWA, studies are considered stage-by-stage with particular focus on quality control as this is by far the most time-consuming and complex issue related to GWA.
Key wordsGenetics Epidemiology Genome-wide Statistics Association
- 22.Clayton DG, Walker NM, Smyth DJ, Pask R, Cooper JD, Maier LM, Smink LJ, Lam AC, Ovington NR, Stevens HE, Nutland S, Howson JMM, Faham M, Moorhead M, Jones HB, Falkowski M, Hardenbol P, Willis TD, Todd JA (2005) Population structure, differential bias and genomic control in a large-scale, case-control association study. Nat Genet 37: 1243–1246.PubMedCrossRefGoogle Scholar
- 30.Bishop DT, Demenais F, Iles MM, Harland M, Taylor JC, Corda E, Randerson-Moor J, Aitken JF, Avril MF, Azizi E, Bakker B, Bianchi-Scarrà G, Bressac-de Paillerets B, Calista D, Cannon-Albright LA, Chin-A-Woeng T, Dębniak T, Galore-Haskel G, Ghiorzo P, Gut I, Hansson J, Hočevar M, Höiom V, Hopper JL, Ingvar C, Kanetsky PA, Kefford RF, Landi MT, Lang J, Lubiński J, Mackie R, Malvehy J, Mann GJ, Martin NG, Montgomery GW, van Nieuwpoort FA, Novakovic S, Olsson H, Puig S, Weiss M, van Workum W, Zelenika D, Brown KM, Goldstein AM, Gillanders EM, Boland A, Galan P, Elder DE, Gruis NA, Hayward NK, Lathrop GM, Barrett JH, Newton Bishop JA (2009) Genome-wide association study identifies three loci associated with melanoma risk. Nat Genet 41(8): 920–925.PubMedCrossRefGoogle Scholar