Distinct Neonatal Brain Anatomy Is Associated With Cross‐Disorder Genetic Risk for Psychiatric Disorders
Year: 2026
Type: article
Study design: Observational Study
Abstract: Psychiatric disorders share a complex polygenic architecture, yet how this genetic liability relates to early brain development remains unclear. This study investigated the associations between cross-disorder polygenic risk and neonatal brain anatomy. We derived three latent psychiatric factors using GenomicSEM, reflecting shared genetic liability among related conditions: A neurodevelopmental factor, a compulsive factor, and a mood-psychosis factor. We then calculated respective polygenic risk scores (PRS) in 336 neonates from the Developing Human Connectome Project. We found that cross-disorder PRSs (neurodevelopmental and mood-psychosis factors) showed significantly broader associations with neonatal brain volumes than disorder-specific PRSs. These associations were highly robust, as confirmed through validation analyses using updated GWAS data and an alternative PRS method (PRS-CS). These cross-disorder PRSs were strongly correlated with smaller global brain size. After accounting for this global effect, associations with a subset of brain regions remained detectable. In exploratory analyses, the neurodevelopmental factor was reproducibly linked to heightened alertness at 18 months. Our results reveal that shared genetic risk for psychiatric disorders manifests as both global and regionally specific variations in brain anatomy at birth, highlighting the value of cross-disorder genetic models for elucidating early neurodevelopmental vulnerability.
Source: Human Brain Mapping
DOI: 10.1002/hbm.70532
Authors: Xixi Dang, Ruiqi Su, Dan Wu, Mingyang Li
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,520
Funders: National Institute for Health and Care Research, European Commission, National Natural Science Foundation of China, Ministry of Science and Technology of the People's Republic of China, Jilin Office of Philosophy and Social Science, National Institutes of Health, Engineering and Physical Sciences Research Council, Centre For Medical Engineering, King’s College London, FP7 Ideas: European Research Council, Natural Science Foundation of Zhejiang Province
Awards: G1144792157, G1247657515, G1911290601, Mapping the Human Connectome: Structure, Function, and Heritability, G4014141827, 测试促进新的学习：儿童发展中的前向测试效应及认知机制, G4067511551, G5296857752, G5537678747, G5651206546, G5893523844, 生物活性S-NO衍生物单电子转移反应的研究, G6666443766, G8303168876, G8775246936, The Developing Human Connectome Project, G938335843, G961285871
OpenAlex ID: W7155006103