Designing candidate gene and genome-wide case-control association studies.
This protocol describes how to appropriately design a genetic association case-control study, either focusing on a candidate gene (CG) or region or implementing a genome-wide approach. The steps described involve: (i) defining the case phenotype in adequate detail; (ii) checking the heritability of the disease in question; (iii) considering whether a population-based study is the appropriate design for the research question; (iv) the appropriate selection of controls; (v) sample size calculations and (vi) giving due consideration to whether it is a de novo or replication study. General guidelines are given, as well as specific examples of a CG 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, CaT, and SNPSpD. Running each of the programs takes only a few seconds; the rate-limiting steps involve thinking through the designs and parameters in the disease models.
Zondervan
Krina T
KT
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. krina.zondervan@well.ox.ac.uk
Cardon
Lon R
LR
D016022:Case-Control Studies; D015340:Epidemiologic Research Design; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D018579:Patient Selection; D011110:Polymorphism, Genetic; D018401:Sample Size; D012984:Software