A structural brain network of genetic vulnerability to psychiatric illness

Details

• Journal Article:
  Mol Psychiatry
• Personal Author:
  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.
• Subjects:
  • Article
• Source:
  Mol Psychiatry.
• DOI:
  http://dx.doi.org/10.1038/s41380-020-0723-7
• Pubmed ID:
  32372008
• Pubmed Central ID:
  PMC7644622
• Document Type:
  Text ; Journal Article
• Funding:
  IDDRC U54 HD090255/U.S. Department of Health & Human Services ; National Institutes of Health (NIH)/ ; S10 OD025111/OD/NIH HHS/United States ; Foundation Fellowship/Royal College of Psychiatrists (RCPsych)/ ; WT_/Wellcome Trust/United Kingdom ; NARSAD Distinguished Investigator award/Brain and Behavior Research Foundation (Brain & Behavior Research Foundation)/ ; R44 MH086984/MH/NIMH NIH HHS/United States ; R01 EB019483/EB/NIBIB NIH HHS/United States ; U54 HD090255/HD/NICHD NIH HHS/United States ; R01 NS079788/NS/NINDS NIH HHS/United States ; Fellowship/Foulkes Foundation/ ; S10 OD025111/CD/ODCDC CDC HHS/United States
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• Genre:
  Journal Article
• Download URL:
  https://stacks.cdc.gov/view/cdc/96807/cdc_96807_DS1.pdf
• File Type:
  [PDF - 874.35 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:0c9a25a5197487f28d4d7d271366db4ec98c6fc39af306a659f3cf5a2d5037c5b66e85981613495af433bf0d46e4d7d39f4d1f52b192ac7127366e941a0580c9