A structural brain network of genetic vulnerability to psychiatric illness

Psychiatry is undergoing a paradigm shift from the acceptance of distinct diagnoses to a representation of psychiatric illness that crosses diagnostic boundaries. How this transition is supported by a shared neurobiology remains largely unknown. In this study, we first identify single nucleotide pol...

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Veröffentlicht in:Molecular psychiatry 2021-06, Vol.26 (6), p.2089-2100
Hauptverfasser: Taquet, Maxime, Smith, Stephen M., Prohl, Anna K., Peters, Jurriaan M., Warfield, Simon K., Scherrer, Benoit, Harrison, Paul J.
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container_end_page 2100
container_issue 6
container_start_page 2089
container_title Molecular psychiatry
container_volume 26
creator Taquet, Maxime
Smith, Stephen M.
Prohl, Anna K.
Peters, Jurriaan M.
Warfield, Simon K.
Scherrer, Benoit
Harrison, Paul J.
description Psychiatry is undergoing a paradigm shift from the acceptance of distinct diagnoses to a representation of psychiatric illness that crosses diagnostic boundaries. How this transition is supported by a shared neurobiology remains largely unknown. In this study, we first identify single nucleotide polymorphisms (SNPs) associated with psychiatric disorders based on 136 genome-wide association studies. We then conduct a joint analysis of these SNPs and brain structural connectomes in 678 healthy children in the PING study. We discovered a strong, robust, and transdiagnostic mode of genome–connectome covariation which is positively and specifically correlated with genetic risk for psychiatric illness at the level of individual SNPs. Similarly, this mode is also significantly positively correlated with polygenic risk scores for schizophrenia, alcohol use disorder, major depressive disorder, a combined bipolar disorder-schizophrenia phenotype, and a broader cross-disorder phenotype, and significantly negatively correlated with a polygenic risk score for educational attainment. The resulting “vulnerability network” is shown to mediate the influence of genetic risks onto behaviors related to psychiatric vulnerability (e.g., marijuana, alcohol, and caffeine misuse, perceived stress, and impulsive behavior). Its anatomy overlaps with the default-mode network, with a network of cognitive control, and with the occipital cortex. These findings suggest that the brain vulnerability network represents an endophenotype funneling genetic risks for various psychiatric illnesses through a common neurobiological root. It may form part of the neural underpinning of the well-recognized but poorly explained overlap and comorbidity between psychiatric disorders.
doi_str_mv 10.1038/s41380-020-0723-7
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subjects 45/43
59/57
692/53/2423
692/699/476
Behavioral Sciences
Biological Psychology
Bipolar disorder
Bipolar Disorder - genetics
Brain
Caffeine
Cannabis
Cognitive ability
Depressive Disorder, Major - genetics
Development and progression
Genetic aspects
Genetic Predisposition to Disease - genetics
Genetic susceptibility
Genome-wide association studies
Genome-Wide Association Study
Genomes
Health aspects
Humans
Impulsive behavior
Medicine
Medicine & Public Health
Mental disorders
Mental Disorders - genetics
Mental illness
Multifactorial Inheritance - genetics
Nervous system
Neural circuitry
Neurosciences
Occipital lobe
Pharmacotherapy
Phenotypes
Psychiatric research
Psychiatry
Risk factors
Schizophrenia
Single-nucleotide polymorphism
title A structural brain network of genetic vulnerability to psychiatric illness
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