title: Assessing the utility of intermediate phenotypes for genetic mapping of psychiatric disease.
abstract: Intermediate phenotypes are traits positioned somewhere between genetic variation and disease. They represent a target for attempts to find disease-associated genetic variants and elucidation of mechanisms. Psychiatry has been particularly enamoured with intermediate phenotypes, due to uncertainty about disease aetiology, inconclusive results in early psychiatric genetic studies, and their appeal relative to traditional diagnostic categories. In this review, we argue that new genetic findings are relevant to the question of the utility of these constructs. In particular, results from genome-wide association studies of psychiatric disorders now allow an assessment of the potential role of particular intermediate phenotypes. Based on such an analysis, as well as other recent results, we conclude that intermediate phenotypes are likely to be most valuable in understanding mechanism.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK. Electronic address: jf@well.ox.ac.uk.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Flint
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Timpson
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK; UK Centre for Tobacco and Alcohol Studies and School of Experimental Psychology, University of Bristol, Bristol BS8 1TU, UK.
authors.forename: Marcus
authors.initials: M
authors.lastname: Munafò
mesh_terms: D002874:Chromosome Mapping / Q000379:methods; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D001523:Mental Disorders / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics