Dimensional and transdiagnostic phenotypes in psychiatric genome-wide association studies

Monika A. Waszczuk*, Katherine G. Jonas, Marina Bornovalova, Gerome Breen, Cynthia M. Bulik, Anna R. Docherty, Thalia C. Eley, John M. Hettema, Roman Kotov, Robert F. Krueger, Todd Lencz, James J. Li, Evangelos Vassos, Irwin D. Waldman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
38 Downloads (Pure)


Genome-wide association studies (GWAS) provide biological insights into disease onset and progression and have potential to produce clinically useful biomarkers. A growing body of GWAS focuses on quantitative and transdiagnostic phenotypic targets, such as symptom severity or biological markers, to enhance gene discovery and the translational utility of genetic findings. The current review discusses such phenotypic approaches in GWAS across major psychiatric disorders. We identify themes and recommendations that emerge from the literature to date, including issues of sample size, reliability, convergent validity, sources of phenotypic information, phenotypes based on biological and behavioral markers such as neuroimaging and chronotype, and longitudinal phenotypes. We also discuss insights from multi-trait methods such as genomic structural equation modelling. These provide insight into how hierarchical ‘splitting’ and ‘lumping’ approaches can be applied to both diagnostic and dimensional phenotypes to model clinical heterogeneity and comorbidity. Overall, dimensional and transdiagnostic phenotypes have enhanced gene discovery in many psychiatric conditions and promises to yield fruitful GWAS targets in the years to come.
Original languageEnglish
Number of pages11
JournalMolecular Psychiatry
Early online date4 Jul 2023
Publication statusE-pub ahead of print - 4 Jul 2023


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