Dimensional and Transdiagnostic Phenotypes in Psychiatric Genome-Wide Association Studies

Details

• Personal Author:
  Bornovalova M ; Breen G ; Bulik CM ; Docherty AR ; Eley TC ; Hettema JM ; Jonas KG ; Kotov R ; Krueger RF ; Lencz T ; Li JJ ; Vassos E ; Waldman ID ; Waszczuk MA
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Biomarkers Genetics Occupational Health Safety
• Keywords:
  Biological Factors Genes Genetic Factors Genomics Psychological Disorders Quantitative Analysis
• ISSN:
  1359-4184
• Document Type:
  Text
• Funding:
  Cooperative Agreement ; Contract
• Genre:
  Journal Article
• Place as Subject:
  Florida ; Georgia ; Illinois ; Minnesota ; New York ; North Carolina ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 5 ; OSHA Region 6 ; OSHA Region 8 ; Texas ; Utah ; Virginia ; Wisconsin
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  28
• Issue:
  12
• NIOSHTIC Number:
  nn:20067930
• Citation:
  Mol Psychiatry 2023 Dec; 28(12):4943-4953
• Contact Point Address:
  Monika A. Waszczuk, Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL
• Email:
  monika.waszczuk@rosalindfranklin.edu
• Federal Fiscal Year:
  2024
• Performing Organization:
  State University of New York - Stony Brook
• Peer Reviewed:
  True
• Start Date:
  20190701
• Source Full Name:
  Molecular Psychiatry
• End Date:
  20210630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8cb4d58632aa7942d5489065356421e8533ae42b4721a19e9a453ceb1ce46af8e471c0ace39a04d06042edaaf0ce4e0a42a6b9355adeb58c274e925b93585463
• Download URL:
  https://stacks.cdc.gov/view/cdc/230164/cdc_230164_DS1.pdf
• File Type:
  [PDF - 1.11 MB ]