Association of genetic and sulcal traits with executive function in congenital heart disease
Abstract Objective Persons with congenital heart disease (CHD) are at increased risk of neurodevelopmental disabilities, including impairments to executive function. Sulcal pattern features correlate with executive function in adolescents with single‐ventricle heart disease and tetralogy of Fallot....
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-02-01
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| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.51950 |
| _version_ | 1827351479053189120 |
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| author | Lara Maleyeff Jane W. Newburger David Wypij Nina H. Thomas Evdokia Anagnoustou Martina Brueckner Wendy K. Chung John Cleveland Sean Cunningham Bruce D. Gelb Elizabeth Goldmuntz Donald J Hagler Jr Hao Huang Eileen King Patrick McQuillen Thomas A. Miller Ami Norris‐Brilliant George A. Porter Jr Amy E. Roberts P. Ellen Grant Kiho Im Sarah U. Morton |
| author_facet | Lara Maleyeff Jane W. Newburger David Wypij Nina H. Thomas Evdokia Anagnoustou Martina Brueckner Wendy K. Chung John Cleveland Sean Cunningham Bruce D. Gelb Elizabeth Goldmuntz Donald J Hagler Jr Hao Huang Eileen King Patrick McQuillen Thomas A. Miller Ami Norris‐Brilliant George A. Porter Jr Amy E. Roberts P. Ellen Grant Kiho Im Sarah U. Morton |
| author_sort | Lara Maleyeff |
| collection | DOAJ |
| description | Abstract Objective Persons with congenital heart disease (CHD) are at increased risk of neurodevelopmental disabilities, including impairments to executive function. Sulcal pattern features correlate with executive function in adolescents with single‐ventricle heart disease and tetralogy of Fallot. However, the interaction of sulcal pattern features with genetic and participant factors in predicting executive dysfunction is unknown. Methods We studied sulcal pattern features, participant factors, and genetic risk for executive function impairment in a cohort with multiple CHD types using stepwise linear regression and machine learning. Results Genetic factors, including predicted damaging de novo or rare inherited variants in neurodevelopmental disabilities risk genes, apolipoprotein E genotype, and principal components of sulcal pattern features were associated with executive function measures after adjusting for age at testing, sex, mother's education, and biventricular versus single‐ventricle CHD in a linear regression model. Using regression trees and bootstrap validation, younger participant age and larger alterations in sulcal pattern features were consistently identified as important predictors of decreased cognitive flexibility with left hemisphere graph topology often selected as the most important predictor. Inclusion of both sulcal pattern and genetic factors improved model fit compared to either alone. Interpretation We conclude that sulcal measures remain important predictors of cognitive flexibility, and the model predicting executive outcomes is improved by inclusion of potential genetic sources of neurodevelopmental risk. If confirmed, measures of sulcal patterning may serve as early imaging biomarkers to identify those at heightened risk for future neurodevelopmental disabilities. |
| first_indexed | 2024-03-08T02:04:59Z |
| format | Article |
| id | doaj.art-8dcae0435919402c9b79af51bd1ffc3c |
| institution | Directory Open Access Journal |
| issn | 2328-9503 |
| language | English |
| last_indexed | 2024-03-08T02:04:59Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj.art-8dcae0435919402c9b79af51bd1ffc3c2024-02-13T18:30:43ZengWileyAnnals of Clinical and Translational Neurology2328-95032024-02-0111227829010.1002/acn3.51950Association of genetic and sulcal traits with executive function in congenital heart diseaseLara Maleyeff0Jane W. Newburger1David Wypij2Nina H. Thomas3Evdokia Anagnoustou4Martina Brueckner5Wendy K. Chung6John Cleveland7Sean Cunningham8Bruce D. Gelb9Elizabeth Goldmuntz10Donald J Hagler Jr11Hao Huang12Eileen King13Patrick McQuillen14Thomas A. Miller15Ami Norris‐Brilliant16George A. Porter Jr17Amy E. Roberts18P. Ellen Grant19Kiho Im20Sarah U. Morton21Department of Biostatistics Harvard T.H. Chan School of Public Health Boston Massachusetts USADepartment of Pediatrics Harvard Medical School Boston Massachusetts USADepartment of Biostatistics Harvard T.H. Chan School of Public Health Boston Massachusetts USADepartment of Child and Adolescent Psychiatry and Behavioral Sciences and Center for Human Phenomic Science Children's Hospital of Philadelphia Philadelphia Pennsylvania USADepartment of Pediatrics Holland Bloorview Kids Rehabilitation Hospital, University of Toronto Toronto Ontario CanadaDepartment of Genetics Yale University School of Medicine New Haven Connecticut USADepartment of Pediatrics Columbia University Medical Center New York New York USADepartment of Surgery, Keck School of Medicine University of Southern California Los Angeles California USADivision of General Pediatrics, Department of Pediatrics University of Utah Salt Lake City Utah USAMindich Child Health and Development Institute and Department of Pediatrics Icahn School of Medicine at Mount Sinai New York New York USADivision of Cardiology, Department of Pediatrics Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania Philadelphia Pennsylvania USACenter for Multimodal Imaging and Genetics University of California San Diego San Diego California USADepartment of Radiology Children's Hospital of Philadelphia, University of Pennsylvania Philadelphia Pennsylvania USADepartment of Pediatrics University of Cincinnati Cincinnati Ohio USADepartment of Pediatrics University of California San Francisco California USADepartment of Pediatrics Primary Children's Hospital, University of Utah Salt Lake City Utah USADepartment of Psychiatry Icahn School of Medicine at Mount Sinai New York New York USADepartment of Pediatrics University of Rochester Medical Center Rochester New York USADepartment of Pediatrics Harvard Medical School Boston Massachusetts USADepartment of Pediatrics Harvard Medical School Boston Massachusetts USADepartment of Pediatrics Harvard Medical School Boston Massachusetts USADepartment of Pediatrics Harvard Medical School Boston Massachusetts USAAbstract Objective Persons with congenital heart disease (CHD) are at increased risk of neurodevelopmental disabilities, including impairments to executive function. Sulcal pattern features correlate with executive function in adolescents with single‐ventricle heart disease and tetralogy of Fallot. However, the interaction of sulcal pattern features with genetic and participant factors in predicting executive dysfunction is unknown. Methods We studied sulcal pattern features, participant factors, and genetic risk for executive function impairment in a cohort with multiple CHD types using stepwise linear regression and machine learning. Results Genetic factors, including predicted damaging de novo or rare inherited variants in neurodevelopmental disabilities risk genes, apolipoprotein E genotype, and principal components of sulcal pattern features were associated with executive function measures after adjusting for age at testing, sex, mother's education, and biventricular versus single‐ventricle CHD in a linear regression model. Using regression trees and bootstrap validation, younger participant age and larger alterations in sulcal pattern features were consistently identified as important predictors of decreased cognitive flexibility with left hemisphere graph topology often selected as the most important predictor. Inclusion of both sulcal pattern and genetic factors improved model fit compared to either alone. Interpretation We conclude that sulcal measures remain important predictors of cognitive flexibility, and the model predicting executive outcomes is improved by inclusion of potential genetic sources of neurodevelopmental risk. If confirmed, measures of sulcal patterning may serve as early imaging biomarkers to identify those at heightened risk for future neurodevelopmental disabilities.https://doi.org/10.1002/acn3.51950 |
| spellingShingle | Lara Maleyeff Jane W. Newburger David Wypij Nina H. Thomas Evdokia Anagnoustou Martina Brueckner Wendy K. Chung John Cleveland Sean Cunningham Bruce D. Gelb Elizabeth Goldmuntz Donald J Hagler Jr Hao Huang Eileen King Patrick McQuillen Thomas A. Miller Ami Norris‐Brilliant George A. Porter Jr Amy E. Roberts P. Ellen Grant Kiho Im Sarah U. Morton Association of genetic and sulcal traits with executive function in congenital heart disease Annals of Clinical and Translational Neurology |
| title | Association of genetic and sulcal traits with executive function in congenital heart disease |
| title_full | Association of genetic and sulcal traits with executive function in congenital heart disease |
| title_fullStr | Association of genetic and sulcal traits with executive function in congenital heart disease |
| title_full_unstemmed | Association of genetic and sulcal traits with executive function in congenital heart disease |
| title_short | Association of genetic and sulcal traits with executive function in congenital heart disease |
| title_sort | association of genetic and sulcal traits with executive function in congenital heart disease |
| url | https://doi.org/10.1002/acn3.51950 |
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