Mapping Risk from Genes to Behavior: The Enduring and Evolving Influence of Irving Gottesman's Endophenotype Concept.
- Authors
- Dick, Danielle M
- Year
- 2018
- Journal
- Twin research and human genetics : the official journal of the International Society for Twin Studies
- PMID
- 30027865
- DOI
- 10.1017/thg.2018.35
One of Irving I. Gottesman's many contributions to behavior genetics, and part of his enduring legacy, was his introduction of the term 'endophenotype' to the field of psychiatry. Gottesman argued that focusing on endophenotypes, rather than complex heterogeneous clinical diagnoses, could help elucidate disease etiology. Although a different strategy for gene identification ultimately proved successful (that of amassing extremely large sample sizes in order to overcome the 'noise' of heterogeneity and have sufficient power to find genes of very small effect), the endophenotype concept continues to make a meaningful contribution to the field. The endophenotype concept forced the field to move beyond a simple disease model of finding genes 'for' psychiatric outcomes, and reminded us that genes are quite distal from complex behavioral outcomes and disorders. Endophenotypes called our attention to the steps along that pathway. In that process, the concept of endophenotypes evolved and expanded to include discussion of the role that other intermediary traits and psychological processes play in the development and genetic etiology of psychiatric and substance use disorders. As large-scale consortia continues to identify genes and generate genome-wide polygenic scores that are associated with behavioral outcomes, the next important step will be to characterize the pathways and mechanisms by which genetic risk unfolds. This essential step of mapping risk from genes to behavior is an evolution that follows naturally from the endophenotype concept, and could ultimately translate into improved prevention and intervention for individuals who are pre-disposed to mental health challenges.
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External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| The association between temperament and polygenic score for psychopathology from infancy to middle childhood. | Freitag E et al. | — | 2025 | → |
| SNAP-25 Polymorphisms in Autism Spectrum Disorder: A Pilot Study towards a Possible Endophenotype. | Mensi MM et al. | — | 2023 | → |
| Genetics in the ADHD Clinic: How Can Genetic Testing Support the Current Clinical Practice? | Balogh L et al. | — | 2022 | → |
| Implications of there being many paths to addiction and recovery. | Lamb RJ et al. | — | 2021 | → |
| Intrinsic functional connectivity in families genetically enriched for social anxiety disorder - an endophenotype study. | Bas-Hoogendam JM et al. | — | 2021 | → |
| Alcohol Sensitivity as an Endophenotype of Alcohol Use Disorder: Exploring Its Translational Utility between Rodents and Humans. | Parker CC et al. | — | 2020 | → |
| Amygdala hyperreactivity to faces conditioned with a social-evaluative meaning- a multiplex, multigenerational fMRI study on social anxiety endophenotypes. | Bas-Hoogendam JM et al. | — | 2020 | → |
| Look duration at the face as a developmental endophenotype: elucidating pathways to autism and ADHD. | Gui A et al. | — | 2020 | → |
| Association of Economic Status and Educational Attainment With Posttraumatic Stress Disorder: A Mendelian Randomization Study. | Polimanti R et al. | — | 2019 | → |