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As psychiatric genetics enters an era where gene identification is finally yielding robust, replicable genetic associations and polygenic risk scores, it is important to consider next steps and delineate how that knowledge will be applied to ultimately ameliorate suffering associated with substance use and psychiatric disorders. Much of the post-genome-wide association study discussion has focused on the potential of genetic information to elucidate the underlying biology and use this information for the development of more effective pharmaceutical treatments. In this review we focus on additional areas of research that should follow gene identification. By taking genetic findings into longitudinal, developmental studies, we can map the pathways by which genetic risk manifests across development, elucidating the early behavioral manifestations of risk, and studying how various environments and interventions moderate that risk across developmental stages. The delineation of risk across development will advance our understanding of mechanism, sex differences and risk and resilience processes in different racial/ethnic groups. Here, we review how the extant twin study literature can be used to guide these efforts. Together, these new lines of research will enable us to develop more informed, tailored prevention and intervention efforts.
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http://dx.doi.org/10.1111/gbb.12447 | DOI Listing |
Brain Behav
September 2025
Pontificia Universidad Javeriana, Facultad De Ciencias, Departamento de Biología, Biología de Plantas y Sistemas Productivos, Bogotá, Colombia.
Introduction: The study explores shared genetic architecture among major psychiatric disorders-major depressive disorder, bipolar disorder, schizophrenia, and post-traumatic stress disorder-emphasizing their overlapping molecular pathways. Using public datasets, we identified shared genes and examined their functional implications through protein-protein interaction (PPI) networks and gene set enrichment analysis (GSEA).
Methods: Genes associated with each disorder were identified through the NCBI Gene database.
Nat Genet
September 2025
Department of Neurology, School of Medicine, University of California, Davis, Sacramento, CA, USA.
To understand shared and ancestry-specific genetic control of brain protein expression and its ramifications for disease, we mapped protein quantitative trait loci (pQTLs) in 1,362 brain proteomes from African American, Hispanic/Latin American and non-Hispanic white donors. Among the pQTLs that multiancestry fine-mapping MESuSiE confidently assigned as putative causal pQTLs in a specific population, most were shared across the three studied populations and are referred to as multiancestry causal pQTLs. These multiancestry causal pQTLs were enriched for exonic and promoter regions.
View Article and Find Full Text PDFNeuropsychopharmacol Rep
September 2025
Department of Neuropsychiatry, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Controlling for confounding factors in postmortem brain studies of psychiatric disorders is crucial, particularly in gene expression analyses. Potential confounding factors include sex, age at death, medication history, agonal state, postmortem interval (PMI), tissue storage duration, tissue pH, and RNA integrity number (RIN). pH and RIN are considered particularly important in gene expression analysis because they accurately reflect mRNA quality.
View Article and Find Full Text PDFBrief Funct Genomics
January 2025
School of Mathematics and Statistics, Henan University of Science and Technology, No. 263 Kaiyuan Avenue, Luolong District, Luoyang, Henan 471000, China.
Background: Comorbidities and genetic correlations between gastrointestinal tract diseases and psychiatric disorders have been widely reported, but the underlying intrinsic link between Alzheimer's disease (AD) and inflammatory bowel disease (IBD) is not adequately understood.
Methods: To identify pathogenic cell types of AD and IBD and explore their shared genetic architecture, we developed Pathogenic Cell types and shared Genetic Loci (PCGL) framework, which studied AD and IBD and its two subtypes of ulcerative colitis (UC) and Crohn's disease (CD).
Results: We found that monocytes and CD8 T cells were the enriched pathogenic cell types of AD and IBDs, respectively.
Front Psychiatry
August 2025
Statistics Section of the Department of Genetics, Microbiology and Statistics, Universitat de Barcelona (UB), Barcelona, Spain.
Most methodological Polygenic Risk Score (PRS)-related papers explain the laborious process of computing the PRS in great depth. Afterwards, as a last step, it is generally described that to test a possible association between a PRS and a trait of interest, an analysis through regression models (linear or logistic, depending on data type) should be carried out adjusting for covariates (e.g.
View Article and Find Full Text PDF