Philip R Jansen1, Ryan L Muetzel2, Tinca J C Polderman3, Vincent W Jaddoe4, Frank C Verhulst2, Aad van der Lugt5, Henning Tiemeier6, Danielle Posthuma7, Tonya White8. 1. Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, The Netherlands. 2. Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands. 3. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, The Netherlands. 4. Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Pediatrics, Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, The Netherlands. 5. Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands. 6. Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 7. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, The Netherlands; Department of Clinical Genetics, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands. 8. Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: t.white@erasmusmc.nl.
Abstract
BACKGROUND: Genome-wide association studies have identified numerous genetic variants that predispose to neuropsychiatric traits. Identification of mechanisms in the brain that underlie these associations is essential for understanding manifestations of genetic predisposition within the general population. Here, we investigated the association between polygenic scores (PGSs) for seven neuropsychiatric traits and white matter microstructure of the brain on diffusion tensor imaging in the pediatric population. METHODS: Participants from the Generation R Study who had genotype and diffusion tensor imaging data available (n = 1138, mean age = 10.2 years, range = 8.7-12.0) were included. PGSs were calculated for five psychiatric disorders (attention-deficit/hyperactivity disorder, bipolar disorder, autism, major depressive disorder, and schizophrenia) and two cognitive traits (intelligence and educational attainment) and were tested for associations with global and tract-specific fractional anisotropy (FA) and mean diffusivity. RESULTS: Significant positive associations with global FA were observed for the PGSs of intelligence (β = .109, SE = .029, p < .001, ΔR2 = .012) and educational attainment (β = .118, SE = .029, p < .001, ΔR2 = .014). No significant associations were observed with FA for the PGSs of psychiatric disorders. Tract-specific analysis showed that the PGSs for intelligence and educational attainment were associated with FA of several association and projection fibers of the brain. CONCLUSIONS: Our results show that genetic predisposition for cognition-related traits, but not for psychiatric disorders, is associated with microstructural diffusion measures of white matter tracts at an early age. These results suggest a shared genetic etiology among structural connectivity, intelligence, and educational achievement.
BACKGROUND: Genome-wide association studies have identified numerous genetic variants that predispose to neuropsychiatric traits. Identification of mechanisms in the brain that underlie these associations is essential for understanding manifestations of genetic predisposition within the general population. Here, we investigated the association between polygenic scores (PGSs) for seven neuropsychiatric traits and white matter microstructure of the brain on diffusion tensor imaging in the pediatric population. METHODS:Participants from the Generation R Study who had genotype and diffusion tensor imaging data available (n = 1138, mean age = 10.2 years, range = 8.7-12.0) were included. PGSs were calculated for five psychiatric disorders (attention-deficit/hyperactivity disorder, bipolar disorder, autism, major depressive disorder, and schizophrenia) and two cognitive traits (intelligence and educational attainment) and were tested for associations with global and tract-specific fractional anisotropy (FA) and mean diffusivity. RESULTS: Significant positive associations with global FA were observed for the PGSs of intelligence (β = .109, SE = .029, p < .001, ΔR2 = .012) and educational attainment (β = .118, SE = .029, p < .001, ΔR2 = .014). No significant associations were observed with FA for the PGSs of psychiatric disorders. Tract-specific analysis showed that the PGSs for intelligence and educational attainment were associated with FA of several association and projection fibers of the brain. CONCLUSIONS: Our results show that genetic predisposition for cognition-related traits, but not for psychiatric disorders, is associated with microstructural diffusion measures of white matter tracts at an early age. These results suggest a shared genetic etiology among structural connectivity, intelligence, and educational achievement.
Authors: Sander Lamballais; Philip R Jansen; Jeremy A Labrecque; M Arfan Ikram; Tonya White Journal: Hum Brain Mapp Date: 2021-02-02 Impact factor: 5.038