Psychophysiological endophenotypes to characterize mechanisms of known schizophrenia genetic loci.
- Authors
- Liu, M; Malone, S M; Vaidyanathan, U; Keller, M C; Abecasis, G; McGue, M; Iacono, W G; Vrieze, S I
- Year
- 2017
- Journal
- Psychological medicine
- PMID
- 27995817
- DOI
- 10.1017/S0033291716003184
- PMCID
- PMC5352523
BACKGROUND: Endophenotypes are laboratory-based measures hypothesized to lie in the causal chain between genes and clinical disorder, and to serve as a more powerful way to identify genes associated with the disorder. One promise of endophenotypes is that they may assist in elucidating the neurobehavioral mechanisms by which an associated genetic polymorphism affects disorder risk in complex traits. We evaluated this promise by testing the extent to which variants discovered to be associated with schizophrenia through large-scale meta-analysis show associations with psychophysiological endophenotypes. METHOD: We genome-wide genotyped and imputed 4905 individuals. Of these, 1837 were whole-genome-sequenced at 11× depth. In a community-based sample, we conducted targeted tests of variants within schizophrenia-associated loci, as well as genome-wide polygenic tests of association, with 17 psychophysiological endophenotypes including acoustic startle response and affective startle modulation, antisaccade, multiple frequencies of resting electroencephalogram (EEG), electrodermal activity and P300 event-related potential. RESULTS: Using single variant tests and gene-based tests we found suggestive evidence for an association between contactin 4 (CNTN4) and antisaccade and P300. We were unable to find any other variant or gene within the 108 schizophrenia loci significantly associated with any of our 17 endophenotypes. Polygenic risk scores indexing genetic vulnerability to schizophrenia were not related to any of the psychophysiological endophenotypes after correction for multiple testing. CONCLUSIONS: The results indicate significant difficulty in using psychophysiological endophenotypes to characterize the genetically influenced neurobehavioral mechanisms by which risk loci identified in genome-wide association studies affect disorder risk.
Correlations between schizophrenia polygenic risk scores (PRS) and each of the endophenotypes. To avoid clutter and improve readability, the figure is organized into four panels, where each panel shares the x and y axes. No correlation between polygenic risk and any endophenotype was significant after accounting for multiple testing. EEG, Electroencephalogram.
No entities extracted from this document yet.
| Filename | Size | Added | |
|---|---|---|---|
| 27995817.pdf | 284060 bytes | 2026-05-15 | View |
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Examining associations between genetic and neural risk for externalizing behaviors in adolescence and early adulthood. | Brislin SJ et al. | — | 2024 | → |
| P300 in schizophrenia: Then and now. | Hamilton HK et al. | — | 2024 | → |
| Inferring the Genetic Influences on Psychological Traits Using MRI Connectivity Predictive Models: Demonstration with Cognition. | Hatoum AS et al. | — | 2023 | → |
| Using multivariate endophenotypes to identify psychophysiological mechanisms associated with polygenic scores for substance use, schizophrenia, and education attainment. | Harper J et al. | — | 2022 | → |
| Network Effects of the 15q13.3 Microdeletion on the Transcriptome and Epigenome in Human-Induced Neurons. | Zhang S et al. | — | 2021 | → |
| The association of polygenic risk for schizophrenia, bipolar disorder, and depression with neural connectivity in adolescents and young adults: examining developmental and sex differences. | Meyers JL et al. | — | 2021 | → |
| The polygenic risk for obsessive-compulsive disorder is associated with the personality trait harm avoidance. | Bey K et al. | — | 2020 | → |
| Network effects of the neuropsychiatric 15q13.3 microdeletion on the transcriptome and epigenome in human induced neurons | Zhang S et al. | — | 2019 | — |
| Target-related parietal P3 and medial frontal theta index the genetic risk for problematic substance use. | Harper J et al. | — | 2019 | → |
| Visual working memory encoding in schizophrenia and first-degree relatives: neurofunctional abnormalities and impaired consolidation. | Stäblein M et al. | — | 2019 | → |
| A polygenic risk score analysis of psychosis endophenotypes across brain functional, structural, and cognitive domains. | Ranlund S et al. | — | 2018 | → |
| Higher-order language dysfunctions as a possible neurolinguistic endophenotype for schizophrenia: Evidence from patients and their unaffected first degree relatives. | Pawełczyk A et al. | — | 2018 | → |
| Meta-analysis on the association between genetic polymorphisms and prepulse inhibition of the acoustic startle response. | Quednow BB et al. | — | 2018 | → |
| Polygenic Risk Scores in Clinical Psychology: Bridging Genomic Risk to Individual Differences. | Bogdan R et al. | — | 2018 | → |
| Proper conditional analysis in the presence of missing data: Application to large scale meta-analysis of tobacco use phenotypes. | Jiang Y et al. | — | 2018 | → |
| Slow Binocular Rivalry as a Potential Endophenotype of Schizophrenia. | Xiao G et al. | — | 2018 | → |
| The utility of twins in developmental cognitive neuroscience research: How twins strengthen the ABCD research design. | Iacono WG et al. | — | 2018 | → |
| A review of endophenotypes in schizophrenia and autism: The next phase for understanding genetic etiologies. | DiLalla LF et al. | — | 2017 | → |