title: Genetic association studies of complex neurological diseases.
abstract: Genetic association studies offer a powerful approach to identify the multiple variants of small effect that modulate susceptibility to common, complex disease. They, however, have a poor reputation, mainly because of the consistent lack of replication of all but a few. Thousands of genetic studies have been carried out on multifactorial diseases in the past 30 years, yielding only about 50 variants that can be considered to be true positives. Although the positive studies show proof of principle, the multitude of negative studies indicate fundamental problems in the design and execution of association studies. Here, we discuss some of the more pertinent study design and data analysis issues which can affect the outcome of genetic association studies.
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: P M
authors.initials: PM
authors.lastname: Abou-Sleiman
authors.forename: M G
authors.initials: MG
authors.lastname: Hanna
authors.forename: N W
authors.initials: NW
authors.lastname: Wood
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D003710:Demography; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009422:Nervous System Diseases / Q000235:genetics*; D012107:Research Design; D018401:Sample Size