Psychological Medicine



Invited Review

The endophenotype concept in psychiatric genetics


JONATHAN FLINT a1 and MARCUS R. MUNAFÒ a2c1
a1 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
a2 Department of Experimental Psychology, University of Bristol, Bristol, UK

Article author query
flint j   [PubMed][Google Scholar] 
munafo mr   [PubMed][Google Scholar] 

Abstract

The idea that some phenotypes bear a closer relationship to the biological processes that give rise to psychiatric illness than diagnostic categories has attracted considerable interest. Much effort has been devoted to finding such endophenotypes, partly because it is believed that the genetic basis of endophenotypes will be easier to analyse than that of psychiatric disease. This belief depends in part on the assumption that the effect sizes of genetic loci contributing to endophenotypes are larger than those contributing to disease susceptibility, hence increasing the chance that genetic linkage and association tests will detect them. We examine this assumption by applying meta-analytical techniques to genetic association studies of endophenotypes. We find that the genetic effect sizes of the loci examined to date are no larger than those reported for other phenotypes. A review of the genetic architecture of traits in model organisms also provides no support for the view that the effect sizes of loci contributing to phenotypes closer to the biological basis of disease is any larger than those contributing to disease itself. While endophenotype measures may afford greater reliability, it should not be assumed that they will also demonstrate simpler genetic architecture.

(Published Online September 18 2006)


Correspondence:
c1 Department of Experimental Psychology, University of Bristol, 12a Priory Road, Bristol BS8 1TU, UK. (Email: marcus.munafo@bristol.ac.uk)


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