Effects of Epilepsy Polygenic Risk on Brain Structure in Neurotypical Children
Abstract number :
1.238
Submission category :
5. Neuro Imaging / 5A. Structural Imaging
Year :
2022
Submission ID :
2204377
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:24 AM
Authors :
Alexander Ngo, BS – McGill University; Sara Larivière, MSc – McGill University; Valeria Kebets, PhD – McGill University; Serena Fett, N/A – McGill University; Clara Weber, N/A – Lübeck University; Jessica Royer, PsyD – McGill University; Lang Liu, MSc – McGill University; Eric Yu, BSc – McGill University; Budhachandra Khundrakpam, PhD – McGill University; Alan Evans, PhD – McGill University; Raúl Rodríguez-Cruces, MBBS, PhD – McGill University; Luis Concha, MD, PhD – National Autonomous University of Mexico; Zhiqiang Zhang, MD – Nanjing University; Neda Ladbon-Bernasconi, MD, PhD – McGill University; Birgit Frauscher, MD, PhD – McGill University; Andrea Bernasconi, MD – McGill University; Ziv Gan-Or, MD, PhD – McGill University; Boris Bernhardt, PhD – McGill University
Rationale: Epilepsy is associated with brain-wide network disruptions and complex genetic architectures. With onsets typically in childhood, developmental transitions spanning youth represent sensitive periods in the disorder. Interactions between genetic factors and dynamic structural changes, however, have yet to be considered in the neurodevelopmental features of epilepsy, requiring a departure from the classic case-control paradigm. Here, we assessed the pleiotropic effects of genetic factors for the common epilepsies on brain morphology during typical development. To gain further etiological insights, we investigated its concordance to disease-specific atrophy patterns.
Methods: We analyzed the structural T1w magnetic resonance imaging (MRI) and whole-genome genotyping data of 313 typically developing children (142 females; mean±SD age=11.98±5.16 years) obtained from the Pediatric Imaging, Neurocognition and Genetics (PING) study._x000D_
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PRS-enriched morphology analyses. We derived vertex-wise cortical thickness maps harmonized across sites using ComBat. Polygenic risk scores (PRS) were also computed based on the weighted sum of common genetic risk variants for hippocampal sclerosis (HS) and generalized epilepsy (GE), obtained from latest genome-wide association studies. Surface-based linear models related PRS for HS and GE to the imaging-derived phenotype in pediatric subjects._x000D_
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Relation to disease-specific atrophy. We leveraged the imaging data from four independent case-control datasets of temporal lobe epilepsy (TLE), idiopathic generalized epilepsy (IGE), and healthy controls (HC): (1) ENIGMA-Epilepsy (nTLE/IGE/HC=578/288/1328), (2) Jinling Hospital (nTLE/IGE/HC=107/96/65), (3) Epilepsy and Cognition (nTLE/HC=23/19) and (4) MICA-MICs (nTLE/HC=21/38). Spatial correlations with autocorrelation preserving null models were used to evaluate the correspondence between PRS-associated morphology and TLE- and IGE-specific atrophy maps.
Results: Widespread thinning across the cortex was observed in children with higher PRS for HS (puncorrected < 0.025; Figure 1A). Conversely, morphology-related effects of PRS for GE demonstrated subtle decreases in temporal, occipital, limbic and parietal regions (puncorrected < 0.025; Figure 1B). Comparisons between patterns of PRS-mediated cortical thickness and TLE-specific (Figure 2A) and IGE-specific (Figure 2B) atrophy maps, however, revealed non-significant weak overlap.
Conclusions: These preliminary findings suggest that effects of epilepsy-related polygenic risk may possibly, albeit weak, recapitulate case-control phenotypes in the common epilepsies. As such, follow up analyses with larger datasets that are more specifically enriched for genetic risk for epilepsy are warranted.
Funding: Not applicable
Neuro Imaging