articleNature GeneticsMay 1, 2022BRONZE OA

Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis

ADAndrew D. GrotzingerTTTravis T. MallardWAWonuola A. AkingbuwaHFHill F. IpMJMark J. Adams

University of Colorado Boulder · The University of Texas at Austin · +19 more institutions

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Abstract

We interrogate the joint genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis. We identify four broad factors (neurodevelopmental, compulsive, psychotic and internalizing) that underlie genetic correlations among the disorders and test whether these factors adequately explain their genetic correlations with biobehavioral traits. We introduce stratified genomic structural equation modeling, which we use to identify gene sets that disproportionately contribute to genetic risk sharing. This includes protein-truncating variant-intolerant genes expressed in excitatory and GABAergic brain cells that are enriched for genetic overlap…

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Topics & keywords

Topics
Keywords
  • Genetic architecture
  • Biology
  • Genetics
  • Genome-wide association study
  • Genetic association
  • Psychiatric genetics
  • Gene
  • Schizophrenia (object-oriented programming)
UN Sustainable Development Goals
  • Good health and well-being
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