| Title: | Association of polygenic scores for autism with volumetric MRI phenotypes in cerebellum and brainstem in adults |
| Journal: | Molecular Autism |
| Published: | 7 Aug 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39113134/ |
| DOI: | https://doi.org/10.1186/s13229-024-00611-7 |
| URL: | https://molecularautism.biomedcentral.com/counter/pdf/10.1186/s13229-024-00611-7 |
Publication 12967
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Abstract
Previous research on autism spectrum disorders (ASD) have showed important volumetric alterations in the cerebellum and brainstem. Most of these studies are however limited to case-control studies with small clinical samples and including mainly children or adolescents. Herein, we aimed to explore the association between the cumulative genetic load (polygenic risk score, PRS) for ASD and volumetric alterations in the cerebellum and brainstem, as well as global brain tissue volumes of the brain among adults at the population level. We utilized the latest genome-wide association study of ASD by the Psychiatric Genetics Consortium (18,381 cases, 27,969 controls) and constructed the ASD PRS in an independent cohort, the UK Biobank. Regression analyses controlled for multiple comparisons with the false-discovery rate (FDR) at 5% were performed to investigate the association between ASD PRS and forty-four brain magnetic resonance imaging (MRI) phenotypes among ~ 31,000 participants. Primary analyses included sixteen MRI phenotypes: total volumes of the brain, cerebrospinal fluid (CSF), grey matter (GM), white matter (WM), GM of whole cerebellum, brainstem, and ten regions of the cerebellum (I_IV, V, VI, VIIb, VIIIa, VIIIb, IX, X, CrusI and CrusII). Secondary analyses included twenty-eight MRI phenotypes: the sub-regional volumes of cerebellum including the GM of the vermis and both left and right lobules of each cerebellar region. ASD PRS were significantly associated with the volumes of seven brain areas, whereby higher PRS were associated to reduced volumes of the whole brain, WM, brainstem, and cerebellar regions I-IV, IX, and X, and an increased volume of the CSF. Three sub-regional volumes including the left cerebellar lobule I-IV, cerebellar vermes VIIIb, and X were significantly and negatively associated with ASD PRS. The study highlights a substantial connection between susceptibility to ASD, its underlying genetic etiology, and neuroanatomical alterations of the adult brain.</p>
17 Keywords
- Adult
- Autism Spectrum Disorder
- Autistic Disorder
- Brain Stem
- Case-Control Studies
- Cerebellum
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Gray Matter
- Humans
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Multifactorial Inheritance
- Organ Size
- Phenotype
6 Authors
- Salahuddin Mohammad
- Mélissa Gentreau
- Manon Dubol
- Gull Rukh
- Jessica Mwinyi
- Helgi B. Schiöth
1 Application
| Application ID | Title |
|---|---|
| 30172 | Comorbidities between addiction and mental disorders ? association of genetics, biomarkers and environment (e.g. lifestyle) with mental health and cognitive function |
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