Assessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research

dc.contributor.authorCai, Na
dc.contributor.authorVerhulst, Brad
dc.contributor.authorAndreassen, Ole A.
dc.contributor.authorBuitelaar, Jan
dc.contributor.authorEdenberg, Howard J.
dc.contributor.authorHettema, John M.
dc.contributor.authorGandal, Michael
dc.contributor.authorGrotzinger, Andrew
dc.contributor.authorJonas, Katherine
dc.contributor.authorLee, Phil
dc.contributor.authorMallard, Travis T.
dc.contributor.authorMattheisen, Manuel
dc.contributor.authorNeale, Michael C.
dc.contributor.authorNurnberger, John I., Jr.
dc.contributor.authorPeyrot, Wouter J.
dc.contributor.authorTucker-Drob, Elliot M.
dc.contributor.authorSmoller, Jordan W.
dc.contributor.authorKendler, Kenneth S.
dc.contributor.departmentBiochemistry and Molecular Biology, School of Medicine
dc.date.accessioned2025-04-22T10:23:39Z
dc.date.available2025-04-22T10:23:39Z
dc.date.issued2025
dc.description.abstractPsychiatric disorders are highly comorbid, heritable, and genetically correlated [1-4]. The primary objective of cross-disorder psychiatric genetics research is to identify and characterize both the shared genetic factors that contribute to convergent disease etiologies and the unique genetic factors that distinguish between disorders [4, 5]. This information can illuminate the biological mechanisms underlying comorbid presentations of psychopathology, improve nosology and prediction of illness risk and trajectories, and aid the development of more effective and targeted interventions. In this review we discuss how estimates of comorbidity and identification of shared genetic loci between disorders can be influenced by how disorders are measured (phenotypic assessment) and the inclusion or exclusion criteria in individual genetic studies (sample ascertainment). Specifically, the depth of measurement, source of diagnosis, and time frame of disease trajectory have major implications for the clinical validity of the assessed phenotypes. Further, biases introduced in the ascertainment of both cases and controls can inflate or reduce estimates of genetic correlations. The impact of these design choices may have important implications for large meta-analyses of cohorts from diverse populations that use different forms of assessment and inclusion criteria, and subsequent cross-disorder analyses thereof. We review how assessment and ascertainment affect genetic findings in both univariate and multivariate analyses and conclude with recommendations for addressing them in future research.
dc.eprint.versionFinal published version
dc.identifier.citationCai N, Verhulst B, Andreassen OA, et al. Assessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research [published correction appears in Mol Psychiatry. 2025 Apr;30(4):1715. doi: 10.1038/s41380-025-02914-4.]. Mol Psychiatry. 2025;30(4):1627-1638. doi:10.1038/s41380-024-02878-x
dc.identifier.urihttps://hdl.handle.net/1805/47273
dc.language.isoen_US
dc.publisherSpringer Nature
dc.relation.isversionof10.1038/s41380-024-02878-x
dc.relation.journalMolecular Psychiatry
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePMC
dc.subjectGenetics
dc.subjectDiagnostic markers
dc.subjectPsychiatric disorders
dc.subjectGenetic predisposition to disease
dc.subjectComorbidity
dc.titleAssessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research
dc.typeArticle
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Cai2025Assessment-CCBY.pdf
Size:
962.15 KB
Format:
Adobe Portable Document Format
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
2.04 KB
Format:
Item-specific license agreed upon to submission
Description: