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

Silvia Alemany, Philip R. Jansen, Ryan L. Muetzel, Natália Marques, Hanan El Marroun, Vincent W.V. Jaddoe, Tinca J.C. Polderman, Henning Tiemeier, Danielle Posthuma, Tonya White

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalJournal of the American Academy of Child and Adolescent Psychiatry
DOIs
Publication statusAccepted/In press - 9 Jan 2019

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Cognition Disorders
Attention Deficit Disorder with Hyperactivity
Psychiatry
Pediatrics
Intelligence
Brain
Population
Caudate Nucleus
Genome-Wide Association Study
Genetic Predisposition to Disease
Bipolar Disorder
Neuroimaging
Schizophrenia
Genotype
Magnetic Resonance Imaging
Depression
Phenotype

Keywords

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

Cite this

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title = "Common Polygenic Variations for Psychiatric Disorders and Cognition in Relation to Brain Morphology in the General Pediatric Population",
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",
author = "Silvia Alemany and Jansen, {Philip R.} and Muetzel, {Ryan L.} and Nat{\'a}lia Marques and {El Marroun}, Hanan and Jaddoe, {Vincent W.V.} and Polderman, {Tinca J.C.} and Henning Tiemeier and Danielle Posthuma and Tonya White",
year = "2019",
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journal = "Journal of the American Academy of Child and Adolescent Psychiatry",
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Common Polygenic Variations for Psychiatric Disorders and Cognition in Relation to Brain Morphology in the General Pediatric Population. / Alemany, Silvia; Jansen, Philip R.; Muetzel, Ryan L.; Marques, Natália; El Marroun, Hanan; Jaddoe, Vincent W.V.; Polderman, Tinca J.C.; Tiemeier, Henning; Posthuma, Danielle; White, Tonya.

In: Journal of the American Academy of Child and Adolescent Psychiatry, 09.01.2019, p. 1-8.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Common Polygenic Variations for Psychiatric Disorders and Cognition in Relation to Brain Morphology in the General Pediatric Population

AU - Alemany, Silvia

AU - Jansen, Philip R.

AU - Muetzel, Ryan L.

AU - Marques, Natália

AU - El Marroun, Hanan

AU - Jaddoe, Vincent W.V.

AU - Polderman, Tinca J.C.

AU - Tiemeier, Henning

AU - Posthuma, Danielle

AU - White, Tonya

PY - 2019/1/9

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N2 - 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.

AB - 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.

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