@article{51eb5114d688488f9f526146ec83bd85,
title = "Dimensional and transdiagnostic phenotypes in psychiatric genome-wide association studies",
abstract = "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 {\textquoteleft}splitting{\textquoteright} and {\textquoteleft}lumping{\textquoteright} 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.",
author = "Waszczuk, {Monika A.} and Jonas, {Katherine G.} and Marina Bornovalova and Gerome Breen and Bulik, {Cynthia M.} and Docherty, {Anna R.} and Eley, {Thalia C.} and Hettema, {John M.} and Roman Kotov and Krueger, {Robert F.} and Todd Lencz and Li, {James J.} and Evangelos Vassos and Waldman, {Irwin D.}",
note = "Funding Information: This work was supported by the National Institute of Mental Health (R21 MH123908) and the Centers for Disease Control and Prevention (U01 OH011864). GB, TCE, and EV are part funded by the NIHR Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Funding Information: CM Bulik reports: Shire (grant recipient, Scientific Advisory Board member); Lundbeckfonden (grant recipient); Pearson (author, royalty recipient); Equip Health Inc. (Stakeholder Advisory Board). Other authors declare no conflict of interest. Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2023",
month = jul,
day = "4",
doi = "10.1038/s41380-023-02142-8",
language = "English",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Springer Nature [academic journals on nature.com]",
}