Identifying novel data-driven subgroups in congenital heart disease using multi-modal measures of brain structure

• Published in: NeuroImage (Orlando, Fla.) Vol. 297; p. 120721
• Main Authors: Vandewouw, Marlee M., Norris-Brilliant, Ami, Rahman, Anum, Assimopoulos, Stephania, Morton, Sarah U., Kushki, Azadeh, Cunningham, Sean, King, Eileen, Goldmuntz, Elizabeth, Miller, Thomas A., Thomas, Nina H., Adams, Heather R., Cleveland, John, Cnota, James F., Ellen Grant, P, Goldberg, Caren S., Huang, Hao, Li, Jennifer S., McQuillen, Patrick, Porter, George A., Roberts, Amy E., Russell, Mark W., Seidman, Christine E., Tivarus, Madalina E., Chung, Wendy K., Hagler, Donald J., Newburger, Jane W., Panigrahy, Ashok, Lerch, Jason P, Gelb, Bruce D., Anagnostou, Evdokia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.08.2024; Elsevier Limited; Elsevier
• Subjects: Behavior; Brain architecture; Brain research; Brain structure; Cardiovascular disease; Children & youth; Cognitive ability; Congenital diseases; Congenital heart disease; Consortia; Executive function; Genes; Genetic diversity; Genetics; Genomics; Heart diseases; Heart surgery; Hospitals; Magnetic resonance imaging; Medical imaging; Neural networks; Neurodevelopmental disorders; Neurodevelopmental outcomes; Neuroimaging; Pediatrics; Research ethics; Sensorimotor integration; Substantia alba; Traumatic brain injury; Unsupervised methods; Visual perception; United States > US; San Francisco California; Genetics; Congenital heart disease; Neurodevelopmental outcomes; Brain structure; Unsupervised methods
• ISSN: 1053-8119; 1095-9572; 1095-9572
• DOI: 10.1016/j.neuroimage.2024.120721

•Individuals with CHD are at risk for neurodevelopmental impairments.•Data-driven approaches can uncover links between genetics, neurobiology, and outcome.•Subgroups derived from structural MRI differ by cardiac lesion and language ability.•Diffusion MRI subgroups differ by genomic variation and visual-motor function.•Cardiac lesion and genomic variation have differential impacts on neurobiology. Individuals with congenital heart disease (CHD) have an increased risk of neurodevelopmental impairments. Given the hypothesized complexity linking genomics, atypical brain structure, cardiac diagnoses and their management, and neurodevelopmental outcomes, unsupervised methods may provide unique insight into neurodevelopmental variability in CHD. Using data from the Pediatric Cardiac Genomics Consortium Brain and Genes study, we identified data-driven subgroups of individuals with CHD from measures of brain structure. Using structural magnetic resonance imaging (MRI; N = 93; cortical thickness, cortical volume, and subcortical volume), we identified subgroups that differed primarily on cardiac anatomic lesion and language ability. In contrast, using diffusion MRI (N = 88; white matter connectivity strength), we identified subgroups that were characterized by differences in associations with rare genetic variants and visual-motor function. This work provides insight into the differential impacts of cardiac lesions and genomic variation on brain growth and architecture in patients with CHD, with potentially distinct effects on neurodevelopmental outcomes.