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Mapping associations between polygenic risks for childhood neuropsychiatric disorders, symptoms of attention deficit hyperactivity disorder, cognition and the brain

There are now large-scale data on which common genetic variants confer risk for attention deficit hyperactivity disorder (ADHD). Here, we use mediation analyses to explore how cognitive and neural features might explain the association between common variant (polygenic) risk for ADHD and its core sy...

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Autores principales: Sudre, Gustavo, Frederick, Jennifer, Sharp, Wendy, Ishii-Takahashi, Ayaka, Mangalmurti, Aman, Choudhury, Saadia, Shaw, Philip
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667324/
https://www.ncbi.nlm.nih.gov/pubmed/30700802
http://dx.doi.org/10.1038/s41380-019-0350-3
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author Sudre, Gustavo
Frederick, Jennifer
Sharp, Wendy
Ishii-Takahashi, Ayaka
Mangalmurti, Aman
Choudhury, Saadia
Shaw, Philip
author_facet Sudre, Gustavo
Frederick, Jennifer
Sharp, Wendy
Ishii-Takahashi, Ayaka
Mangalmurti, Aman
Choudhury, Saadia
Shaw, Philip
author_sort Sudre, Gustavo
collection PubMed
description There are now large-scale data on which common genetic variants confer risk for attention deficit hyperactivity disorder (ADHD). Here, we use mediation analyses to explore how cognitive and neural features might explain the association between common variant (polygenic) risk for ADHD and its core symptoms. In total, 544 participants participated (mean 21 years, 212 [39%] with ADHD], most with cognitive assessments, neuroanatomic imaging and imaging of white matter tract microstructure. We found that polygenic risk for ADHD was associated with symptoms of hyperactivity-impulsivity but not inattention. This association was mediated across multiple PRS thresholds by white matter microstructure, specifically by axial diffusivity of the right corona radiata, (maximum indirect effect β = −0.034 [CI. −0.065 to −0.01), by thickness of the left dorsomedial prefrontal [β = −0.029; CI −0.061 to −0.0047]) and area of the right lateral temporal cortex [β = 0.024; CI 0.0034 to 0.054]). Additionally, modest serial mediation was found, mapping a pathway from polygenic risk, to white matter microstructure of the anterior corona radiata, then cognition (working memory, focused attention), and finally to hyperactivity-impulsivity (working memory β = −0.014 [CI. −0.038 to −0.0026]; focused attention β = −0.011 [CI. −0.033 to −0.0017]). These mediation pathways were diagnostically specific and were not found for polygenic risk for ASD or schizophrenia. In conclusion, using a deeply phenotyped cohort, we delineate a pathway from polygenic risk for ADHD to hyperactive-impulsive symptoms through white matter microstructure, cortical anatomy and cognition.
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spelling pubmed-66673242019-07-30 Mapping associations between polygenic risks for childhood neuropsychiatric disorders, symptoms of attention deficit hyperactivity disorder, cognition and the brain Sudre, Gustavo Frederick, Jennifer Sharp, Wendy Ishii-Takahashi, Ayaka Mangalmurti, Aman Choudhury, Saadia Shaw, Philip Mol Psychiatry Article There are now large-scale data on which common genetic variants confer risk for attention deficit hyperactivity disorder (ADHD). Here, we use mediation analyses to explore how cognitive and neural features might explain the association between common variant (polygenic) risk for ADHD and its core symptoms. In total, 544 participants participated (mean 21 years, 212 [39%] with ADHD], most with cognitive assessments, neuroanatomic imaging and imaging of white matter tract microstructure. We found that polygenic risk for ADHD was associated with symptoms of hyperactivity-impulsivity but not inattention. This association was mediated across multiple PRS thresholds by white matter microstructure, specifically by axial diffusivity of the right corona radiata, (maximum indirect effect β = −0.034 [CI. −0.065 to −0.01), by thickness of the left dorsomedial prefrontal [β = −0.029; CI −0.061 to −0.0047]) and area of the right lateral temporal cortex [β = 0.024; CI 0.0034 to 0.054]). Additionally, modest serial mediation was found, mapping a pathway from polygenic risk, to white matter microstructure of the anterior corona radiata, then cognition (working memory, focused attention), and finally to hyperactivity-impulsivity (working memory β = −0.014 [CI. −0.038 to −0.0026]; focused attention β = −0.011 [CI. −0.033 to −0.0017]). These mediation pathways were diagnostically specific and were not found for polygenic risk for ASD or schizophrenia. In conclusion, using a deeply phenotyped cohort, we delineate a pathway from polygenic risk for ADHD to hyperactive-impulsive symptoms through white matter microstructure, cortical anatomy and cognition. 2019-01-30 2020-10 /pmc/articles/PMC6667324/ /pubmed/30700802 http://dx.doi.org/10.1038/s41380-019-0350-3 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Sudre, Gustavo
Frederick, Jennifer
Sharp, Wendy
Ishii-Takahashi, Ayaka
Mangalmurti, Aman
Choudhury, Saadia
Shaw, Philip
Mapping associations between polygenic risks for childhood neuropsychiatric disorders, symptoms of attention deficit hyperactivity disorder, cognition and the brain
title Mapping associations between polygenic risks for childhood neuropsychiatric disorders, symptoms of attention deficit hyperactivity disorder, cognition and the brain
title_full Mapping associations between polygenic risks for childhood neuropsychiatric disorders, symptoms of attention deficit hyperactivity disorder, cognition and the brain
title_fullStr Mapping associations between polygenic risks for childhood neuropsychiatric disorders, symptoms of attention deficit hyperactivity disorder, cognition and the brain
title_full_unstemmed Mapping associations between polygenic risks for childhood neuropsychiatric disorders, symptoms of attention deficit hyperactivity disorder, cognition and the brain
title_short Mapping associations between polygenic risks for childhood neuropsychiatric disorders, symptoms of attention deficit hyperactivity disorder, cognition and the brain
title_sort mapping associations between polygenic risks for childhood neuropsychiatric disorders, symptoms of attention deficit hyperactivity disorder, cognition and the brain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667324/
https://www.ncbi.nlm.nih.gov/pubmed/30700802
http://dx.doi.org/10.1038/s41380-019-0350-3
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