ArticleBiological psychiatry2012
High dimensional endophenotype ranking in the search for major depression risk genes.
Article in Biological psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 3 of them syntheses that pooled it.
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105 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Peripheral Inflammatory Markers in Subtypes and Core Features of Depression: A Systematized Review.Psychopathology · 2023Pooled it
- Shared and distinct brain fMRI response during performance of working memory tasks in adult patients with schizophrenia and major depressive disorder.Human brain mapping · 2021Pooled it
- Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder.PloS one · 2018Pooled it
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- Heritability, phenotypic, and genetic correlations across dimensional and categorical models of bipolar disorder in a family sample.Journal of affective disorders · 2025Article
- Endophenotype 2.0: updated definitions and criteria for endophenotypes of psychiatric disorders, incorporating new technologies and findings.Translational psychiatry · 2024Review
- Review of Intranasal Active Pharmaceutical Ingredient Delivery Systems.Pharmaceuticals (Basel, Switzerland) · 2024Review
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- Strong Genetic Overlaps Between Dimensional and Categorical Models of Bipolar Disorders in a Family Sample.medRxiv : the preprint server for health sciences · 2024Article
- Investigating the genetic relationship of intracranial and subcortical brain volumes with depression and other psychiatric disorders.Imaging neuroscience (Cambridge, Mass.) · 2024Article
- Endophenotype trait domains for advancing gene discovery in autism spectrum disorder.Journal of neurodevelopmental disorders · 2023Review
- Gene-by-Environment Interaction in Non-Alcoholic Fatty Liver Disease and Depression: The Role of Hepatic Transaminases.Medical research archives · 2023Article
- Sex differences in brain volumes and psychological distress: The first hundred brains cohort of the longitudinal adolescent brain study.Neuroimage. Reports · 2023Article
- Cocktail-party listening and cognitive abilities show strong pleiotropy.Frontiers in neurology · 2023Article
- Genetic variant rs9848497 up-regulatesProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- ENIGMA-anxiety working group: Rationale for and organization of large-scale neuroimaging studies of anxiety disorders.Human brain mapping · 2022Review
- Imaging Genetics in Epilepsy: Current Knowledge and New Perspectives.Frontiers in molecular neuroscience · 2022Review
- Transcriptome-wide association study reveals two genes that influence mismatch negativity.Cell reports · 2021Article
45 more citing papers are in PubMed but not listed here.
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Abstract
backgroundDespite overwhelming evidence that major depression is highly heritable, recent studies have localized only a single depression-related locus reaching genome-wide significance and have yet to identify a causal gene. Focusing on family-based studies of quantitative intermediate phenotypes or endophenotypes, in tandem with studies of unrelated individuals using categorical diagnoses, should improve the likelihood of identifying major depression genes. However, there is currently no empirically derived statistically rigorous method for selecting optimal endophentypes for mental illnesses. Here, we describe the endophenotype ranking value, a new objective index of the genetic utility of endophenotypes for any heritable illness.
methodsApplying endophenotype ranking value analysis to a high-dimensional set of over 11,000 traits drawn from behavioral/neurocognitive, neuroanatomic, and transcriptomic phenotypic domains, we identified a set of objective endophenotypes for recurrent major depression in a sample of Mexican American individuals (n = 1122) from large randomly selected extended pedigrees.
resultsTop-ranked endophenotypes included the Beck Depression Inventory, bilateral ventral diencephalon volume, and expression levels of the RNF123 transcript. To illustrate the utility of endophentypes in this context, each of these traits were utlized along with disease status in bivariate linkage analysis. A genome-wide significant quantitative trait locus was localized on chromsome 4p15 (logarithm of odds = 3.5) exhibiting pleiotropic effects on both the endophenotype (lymphocyte-derived expression levels of the RNF123 gene) and disease risk.
conclusionsThe wider use of quantitative endophenotypes, combined with unbiased methods for selecting among these measures, should spur new insights into the biological mechanisms that influence mental illnesses like major depression.
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