TY - JOUR
T1 - Polygenic Scores for Neuropsychiatric Traits and White Matter Microstructure in the Pediatric Population
AU - Jansen, Philip R
AU - Muetzel, Ryan L
AU - Polderman, Tinca J C
AU - Jaddoe, Vincent W
AU - Verhulst, Frank C
AU - van der Lugt, Aad
AU - Tiemeier, Henning
AU - Posthuma, Danielle
AU - White, Tonya
N1 - Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
KW - Brain/pathology
KW - Child
KW - Children
KW - Cognition
KW - Cognition/physiology
KW - DTI
KW - Female
KW - Genetic Predisposition to Disease
KW - Humans
KW - Male
KW - Mental Disorders/genetics
KW - Multifactorial Inheritance
KW - Neural Pathways/pathology
KW - Polygenic scores
KW - Psychiatric disorders
KW - White Matter/pathology
KW - White matter
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U2 - https://doi.org/10.1016/j.bpsc.2018.07.010
DO - https://doi.org/10.1016/j.bpsc.2018.07.010
M3 - Article
C2 - 30243642
SN - 2451-9022
VL - 4
SP - 243
EP - 250
JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
IS - 3
ER -