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Shared genetic architecture across psychiatric disorders

Published online by Cambridge University Press:  17 March 2021

Andrew D. Grotzinger Open the ORCID record for Andrew D. Grotzinger [Opens in a new window]
Andrew D. Grotzinger*
Affiliation:
Department of Psychology, University of Texas at Austin, Austin, TX, USA Psychiatric and Neurodevelopmental Genetics Unit (PNGU) and the Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
*
Author for correspondence: Andrew D. Grotzinger, E-mail: [email protected]
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Abstract

Psychiatric disorders overlap substantially at the genetic level, with family-based methods long pointing toward transdiagnostic risk pathways. Psychiatric genomics has progressed rapidly in the last decade, shedding light on the biological makeup of cross-disorder risk at multiple levels of analysis. Over a hundred genetic variants have been identified that affect multiple disorders, with many more to be uncovered as sample sizes continue to grow. Cross-disorder mechanistic studies build on these findings to cluster transdiagnostic variants into meaningful categories, including in what tissues or when in development these variants are expressed. At the upper-most level, methods have been developed to estimate the overall shared genetic signal across pairs of traits (i.e. single-nucleotide polymorphism-based genetic correlations) and subsequently model these relationships to identify overarching, genomic risk factors. These factors can subsequently be associated with external traits (e.g. functional imaging phenotypes) to begin to understand the makeup of these transdiagnostic risk factors. As psychiatric genomic efforts continue to expand, we can begin to gain even greater insight by including more fine-grained phenotypes (i.e. symptom-level data) and explicitly considering the environment. The culmination of these efforts will help to inform bottom-up revisions of our current nosology.

Keywords

Comorbiditycross-disorder genomicsGWASpleiotropypsychiatric genetics
Type
Invited Review
Information
Psychological Medicine , Volume 51 , Special Issue 13: Updates on the Genetics of Major Psychiatric Disorders by Early Career Investigators from the Psychiatric Genomics Consortium , October 2021 , pp. 2210 - 2216
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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