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Cai, N. ; Verhulst, B.* ; Andreassen, O.A.* ; Buitelaar, J.K.* ; Edenberg, H.J.* ; Hettema, J.M.* ; Gandal, M.* ; Grotzinger, A.* ; Jonas, K.* ; Lee, P.* ; Mallard, T.T.* ; Mattheisen, M.* ; Neale, M.C.* ; Nurnberger, J.I.* ; Peyrout, W.* ; Tucker-Drob, E.M.* ; Smoller, J.W.* ; Kendler, K.S.*

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

Mol. Psychiatry, DOI: 10.1038/s41380-024-02878-x (2024)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Psychiatric 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Schlagwörter Genome-wide Association; Uk Biobank; Major Depression; Selection Bias; Risk-factors; Schizophrenia; Diagnoses; Validity; Prevalence; Interview
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 1359-4184
e-ISSN 1476-5578
Zeitschrift Molecular Psychiatry
Verlag Nature Publishing Group
Verlagsort Campus, 4 Crinan St, London, N1 9xw, England
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Pioneer Campus (HPC)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Pioneer Campus
PSP-Element(e) G-510007-001
Förderungen Horizon2020
Research Council of Norway
Sunovion
Brain and Behavior Research Foundation
NIH
KG Jebsen Stiftelsen
SFARI
Autistica
European Federation of Pharmaceutical Industries and Associations (EFPIA)
European Union's FP7
Innovative Medicines Initiative Joint Undertaking
EU-AIMS (European Autism Interventions)
European Union's Horizon 2020 RIA
U.S. Department of Health & Human Services | National Institutes of Health (NIH)
DOI 10.1038/s41380-024-02878-x
WOS ID 001385061700001
Scopus ID 85213717993
PubMed ID 39730880
Erfassungsdatum 2025-01-10
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