The endophenotype concept in psychiatric genetics
Open accessAbstract
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.
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The Met allele is associated with fewer perseverative errors in healthy individuals.
“Better working memory (WM) performance (e.g. in N-back tasks), fewer perseverative errors, and higher IQ tend to be associated with the Met allele in healthy individuals (9-11), although some studies have failed to replicate these effects (see 10).”
From Influence of the COMT genotype on working memory and brain activity changes during development (2011) · cites this paper as [11]
The Met allele is associated with higher IQ in healthy individuals.
“Better working memory (WM) performance (e.g. in N-back tasks), fewer perseverative errors, and higher IQ tend to be associated with the Met allele in healthy individuals (9-11), although some studies have failed to replicate these effects (see 10).”
From Influence of the COMT genotype on working memory and brain activity changes during development (2011) · cites this paper as [11]
The Met allele is associated with better working memory performance in healthy individuals.
“Better working memory (WM) performance (e.g. in N-back tasks), fewer perseverative errors, and higher IQ tend to be associated with the Met allele in healthy individuals (9-11), although some studies have failed to replicate these effects (see 10).”
From Influence of the COMT genotype on working memory and brain activity changes during development (2011) · cites this paper as [11]
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- Authors
- FLINT, J., & MUNAFÒ, M. R.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2006-09-18
- Volume
- 37
- Issue
- 2
- Pages
- 163-180
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- PMC
- PMC2829981
- OpenAlex
- W2115948763
- Cited by
- 477
- References
- 143
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 8 · 2023: 6 · 2022: 4 · 2021: 11 · 2020: 19 · 2019: 20 · 2018: 17 · 2017: 23 · 2016: 31 · 2015: 27 · 2014: 29 · 2013: 36 · 2012: 28
- FWCI
- 5.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Psychological Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- endophenotypes, psychiatric genetics, genetic effect size, genetic association studies, genetic linkage, genetic architecture, model organisms, diagnostic categories
- MeSH terms
- Mental Disorders, Catechol O-Methyltransferase, Genotype, Humans, Models, Genetic, Models, Psychological, Phenotype, Psychiatry, Psychotic Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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