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 |
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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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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.</description><identifier>ISSN: 1359-4184</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/s41380-020-0723-7</identifier><identifier>PMID: 32372008</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>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</subject><ispartof>Molecular psychiatry, 2021-06, Vol.26 (6), p.2089-2100</ispartof><rights>The Author(s) 2020</rights><rights>2020. The Author(s).</rights><rights>COPYRIGHT 2021 Nature Publishing Group</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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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. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Taquet, Maxime</au><au>Smith, Stephen M.</au><au>Prohl, Anna K.</au><au>Peters, Jurriaan M.</au><au>Warfield, Simon K.</au><au>Scherrer, Benoit</au><au>Harrison, Paul J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A structural brain network of genetic vulnerability to psychiatric illness</atitle><jtitle>Molecular psychiatry</jtitle><stitle>Mol Psychiatry</stitle><addtitle>Mol Psychiatry</addtitle><date>2021-06-01</date><risdate>2021</risdate><volume>26</volume><issue>6</issue><spage>2089</spage><epage>2100</epage><pages>2089-2100</pages><issn>1359-4184</issn><eissn>1476-5578</eissn><abstract>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. 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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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