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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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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. |
format | Online Article Text |
id | pubmed-6667324 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
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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