Imaging Genetics and Genomics in Psychiatry: A Critical Review of Progress and Potential

Abstract

Imaging genetics and genomics research has begun to provide insight into the molecular and genetic architecture of neural phenotypes and the neural mechanisms through which genetic risk for psychopathology may emerge. As it approaches its third decade, imaging genetics is confronted by many challenges including the proliferation of studies using small sample sizes and diverse designs, limited replication, problems with harmonization of neural phenotypes for meta-analysis, unclear mechanisms, and evidence that effect sizes may be more modest than originally posited, with increasing evidence of polygenicity. These concerns have encouraged the field to grow in many new directions including the development of consortia and large scale data collection projects as well as the use of novel methods (e.g., polygenic approaches, machine learning), which enhance the quality of imaging genetic studies, but also introduce new challenges. Here, we critically review progress in imaging genetics and offer suggestions and highlight potential pitfalls of novel approaches. Ultimately, the strength of imaging genetics and genomics lies in its translational and integrative potential with other research approaches (e.g., non-human animal models, psychiatric genetics, pharmacologic challenge) to elucidate brain-based pathways that give rise to the vast individual differences in behavior as well as risk for psychopathology.

Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function

“…While the BIMPS approach has multiple strengths including a polygenic approach and reliance on prior literature, it is also faced with challenges (Bogdan et al, in press). This approach is reliant upon prior functional associations with particular polymorphisms, which could reasonably only be employed in a handful of systems.…”

Psychiatry and developmental psychopathology: Unifying themes and future directions

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Mapping causal pathways from genetics to neuropsychiatric disorders using genome‐wide imaging genetics: Current status and future directions

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