ArticleEBioMedicine2019
A biologically-informed polygenic score identifies endophenotypes and clinical conditions associated with the insulin receptor function on specific brain regions.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.
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Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Pharmacogenomic scores in psychiatry: systematic review of current evidence.Translational psychiatry · 2024Pooled it
- Mental health dished up-the use of iPSC models in neuropsychiatric research.Journal of neural transmission (Vienna, Austria : 1996) · 2020Pooled it
- Hippocampal SGK1 promotes vulnerability to depression: the role of early life adversity, stress, and genetic risk.Molecular psychiatry · 2025Article
- Cerebrospinal fluid markers link to synaptic plasticity responses and Alzheimer's disease genetic pathways.Molecular neurodegeneration · 2025Article
- Brain insulin receptor gene network shapes risk for metabolic disease after early-life stress in women.Communications biology · 2025Article
- Pathway-Specific Polygenic Scores for Predicting Clinical Lithium Treatment Response in Patients With Bipolar Disorder.Biological psychiatry global open science · 2025Article
- A survey on deep learning for polygenic risk scores.Briefings in bioinformatics · 2025Review
- DeepAnnotation: A novel interpretable deep learning-based genomic selection model that integrates comprehensive functional annotations.GigaScience · 2025Article
- Polygenic scores and antidepressant treatment outcomes in major depression: a critical integrative review.Neuroscience applied · 2025Article
- Striatal dopamine gene network moderates the effect of early adversity on the risk for adult psychiatric and cardiometabolic comorbidity.Scientific reports · 2024Article
- Biologically Informed Polygenic Scores for Brain Insulin Receptor Network Are Associated with Cardiometabolic Risk Markers and Diabetes in Women.Diabetes & metabolism journal · 2024Article
- The brain insulin receptor gene network and associations with frailty index.Age and ageing · 2024Article
- Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes.Nature communications · 2023Article
- Novel Functional Genomics Approaches Bridging Neuroscience and Psychiatry.Biological psychiatry global open science · 2023Review
- Article
- Leptin receptor co-expression gene network moderates the effect of early life adversity on eating behavior in children.Communications biology · 2022Article
- Corticolimbic DCC gene co-expression networks as predictors of impulsivity in children.Molecular psychiatry · 2022Article
- Editorial: Gene and Environment Interactions in Neurodevelopmental Disorders.Frontiers in behavioral neuroscience · 2022Article
- The relationship between health-related quality of life and melancholic depressive symptoms is modified by brain insulin receptor gene network.Scientific reports · 2021Article
- Association of increased abdominal adiposity at birth with altered ventral caudate microstructure.International journal of obesity (2005) · 2021Article
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundActivation of brain insulin receptors modulates reward sensitivity, inhibitory control and memory. Variations in the functioning of this mechanism likely associate with individual differences in the risk for related mental disorders (attention deficit hyperactivity disorder or ADHD, addiction, dementia), in agreement with the high co-morbidity between insulin resistance and psychopathology. These neurobiological mechanisms can be explored using genetic studies. We propose a novel, biologically informed genetic score reflecting the mesocorticolimbic and hippocampal insulin receptor-related gene networks, and investigate if it predicts endophenotypes (impulsivity, cognitive ability) in community samples of children, and psychopathology (addiction, dementia) in adults.
methodsLists of genes co-expressed with the insulin receptor in the mesocorticolimbic system or hippocampus were created. SNPs from these genes (post-clumping) were compiled in a polygenic score using the association betas described in a conventional GWAS (ADHD in the mesocorticolimbic score and Alzheimer in the hippocampal score). Across multiple samples (n = 4502), the biologically informed, mesocorticolimbic or hippocampal specific insulin receptor polygenic scores were calculated, and their ability to predict impulsivity, risk for addiction, cognitive performance and presence of Alzheimer's disease was investigated.
findingsThe biologically-informed ePRS-IR score showed better prediction of child impulsivity and cognitive performance, as well as risk for addiction and Alzheimer's disease in comparison to conventional polygenic scores for ADHD, addiction and dementia.
interpretationThis novel, biologically-informed approach enables the use of genomic datasets to probe relevant biological processes involved in neural function and disorders. FUND: Toxic Stress Research network of the JPB Foundation, Jacobs Foundation (Switzerland), Sackler Foundation.
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