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J Am Acad Child Adolesc Psychiatry. 2019 Jan 9. pii: S0890-8567(19)30007-3. doi: 10.1016/j.jaac.2018.09.443. [Epub ahead of print]

Common Polygenic Variations for Psychiatric Disorders and Cognition in Relation to Brain Morphology in the General Pediatric Population.

Author information

1
Barcelona Institute for Global Health and the Universitat Pompeu Fabra (UPF), Barcelona, Spain and with the CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Electronic address: silvia.alemany@isglobal.org.
2
Erasmus University Medical Center, Rotterdam, the Netherlands; Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands; Amsterdam Neuroscience, VU University, Amsterdam, the Netherlands; Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, the Netherlands.
3
Erasmus University Medical Center, Rotterdam, the Netherlands.
4
Instituto de Biofísica e Engenharia Biomédica, Faculdade de Ciências, Universidade de Lisboa, Portugal.
5
Erasmus University Medical Center, Rotterdam, the Netherlands; Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands.
6
Amsterdam Neuroscience, VU University, Amsterdam, the Netherlands; Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, the Netherlands.
7
Erasmus University Medical Center, Rotterdam, the Netherlands; Harvard TH Chan School of Public Health, Boston, MA.
8
Amsterdam Neuroscience, VU University, Amsterdam, the Netherlands; Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, the Netherlands; VU University Medical Center (VUMC), Amsterdam.

Abstract

OBJECTIVE:

This study examined the relation between polygenic scores (PGSs) for 5 major psychiatric disorders and 2 cognitive traits with brain magnetic resonance imaging morphologic measurements in a large population-based sample of children. In addition, this study tested for differences in brain morphology-mediated associations between PGSs for psychiatric disorders and PGSs for related behavioral phenotypes.

METHOD:

Participants included 1,139 children from the Generation R Study assessed at 10 years of age with genotype and neuroimaging data available. PGSs were calculated for schizophrenia, bipolar disorder, major depression disorder, attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, intelligence, and educational attainment using results from the most recent genome-wide association studies. Image processing was performed using FreeSurfer to extract cortical and subcortical brain volumes.

RESULTS:

Greater genetic susceptibility for ADHD was associated with smaller caudate volume (strongest prior = 0.01: β = -0.07, p = .006). In boys, mediation analysis estimates showed that 11% of the association between the PGS for ADHD and the PGS attention problems was mediated by differences in caudate volume (n = 535), whereas mediation was not significant in girls or the entire sample. PGSs for educational attainment and intelligence showed positive associations with total brain volume (strongest prior = 0.5: β = 0.14, p = 7.12 × 10-8; and β = 0.12, p = 6.87 × 10-7, respectively).

CONCLUSION:

The present findings indicate that the neurobiological manifestation of polygenic susceptibility for ADHD, educational attainment, and intelligence involve early morphologic differences in caudate and total brain volumes in childhood. Furthermore, the genetic risk for ADHD might influence attention problems through the caudate nucleus in boys.

KEYWORDS:

ADHD; educational attainment; intelligence; neuroimaging; polygenic risk score

PMID:
30768412
DOI:
10.1016/j.jaac.2018.09.443

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