The endophenotype concept in psychiatric genetics.
paper
Cited
Public
- Authors
- Flint, Jonathan; MunafΓ², Marcus R
- Year
- 2007
- Journal
- Psychological medicine
- PMID
- 16978446
- DOI
- 10.1017/S0033291706008750
- PMCID
- PMC2829981
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.
Meta-analysis of association of COMT genotype with WCST performance (perseverative errors). Meta-analysis indicates marginal evidence of association between COMT genotype and WCST performance, with a direction of effect consistent with increased perseverative errors in the Val/Met+Val/Val group compared to the Met/Met group. Bars represent individual study 95% confidence intervals, with a central block proportional to study size. The summary diamond bar represents the summary effect size estimate and 95% confidence interval.
Meta-analysis of association of COMT genotype with N-Back performance (2-Back). Meta-analysis indicates marginal evidence of association between COMT genotype and N-Back 2 performance, with a direction of effect consistent with decreased accuracy in the Val/Met+Val/Val group compared to the Met/Met group. Bars represent individual study 95% confidence intervals, with a central block proportional to study size. The summary diamond bar represents the summary effect size estimate and 95% confidence interval.
Meta-analysis of association of COMT genotype with P300 amplitude and latency. Meta-analysis indicates no evidence of association between COMT genotype and P300 amplitude (a) and latency (b), with a direction of effect consistent with increased amplitude and latency in the Val/Met+Val/Val group compared to the Met/Met group. Bars represent individual study 95% confidence intervals, with a central block proportional to study size. The summary diamond bar represents the summary effect size estimate and 95% confidence interval.
Distribution of effect sizes of 843 mouse quantitative trait loci (QTL).
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In this knowledge base
External
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