Dimensional and transdiagnostic phenotypes in psychiatric genome-wide association studies.
Dimensional and transdiagnostic phenotypes in psychiatric genome-wide association studies.
复制标题
DOI：
10.1038/s41380-023-02142-8
复制
发表时间：
2023-07
影响因子：
11
通讯作者：
M. Waszczuk;Katherine G. Jonas;M. Bornovalova;G. Breen;C. Bulik;A. Docherty;T. Eley;J. Hettema;R. Kotov;R. Krueger;T. Lencz;J. J. Li-J.;E. Vassos;I. Waldman
中科院分区：
文献类型：
--
作者：
M. Waszczuk;Katherine G. Jonas;M. Bornovalova;G. Breen;C. Bulik;A. Docherty;T. Eley;J. Hettema;R. Kotov;R. Krueger;T. Lencz;J. J. Li-J.;E. Vassos;I. Waldman
全基因组关联研究（GWAS）为疾病的发生和进展提供了生物学见解，并有可能产生临床有用的生物标志物。越来越多的GWAS专注于定量和转诊断表型靶点，如症状严重程度或生物标志物，以增强基因发现和遗传发现的转化效用。目前的审查讨论了这种表型的方法在GWAS在主要的精神疾病。我们确定的主题和建议，从文献中出现的日期，包括样本量，可靠性，收敛效度，表型信息的来源，表型的基础上的生物和行为标记，如神经影像学和时间型，和纵向表型的问题。我们还讨论了多性状方法的见解，如基因组结构方程模型。这些提供了深入了解分层“分裂”和“集总”的方法可以应用于诊断和维度表型，以模拟临床异质性和合并症。总的来说，维度和转诊断表型增强了许多精神疾病的基因发现，并有望在未来几年产生富有成效的GWAS目标。
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.