Normal cerebral cortical thickness in first-degree relatives of temporal lobe epilepsy patients.
2019; 92 (4): e351–e358
To examine cerebral cortex thickness in asymptomatic first-degree relatives of patients with mesial temporal lobe epilepsy (MTLE).We investigated 127 asymptomatic first-degree relatives of patients with MTLE due to hippocampal sclerosis (HS) (mean age ± SD = 39.4 ± 13 years) and 203 healthy control individuals (mean age ± SD = 36.0 ± 11 years). Participants underwent a comprehensive clinical evaluation and structural brain MRI at 3 study sites. Images were processed simultaneously at each site using a surface-based morphometry method to quantify global brain measures, hippocampal volumes, and cerebral cortical thickness. Differences in brain measures between relatives of patients and controls were examined using generalized models, while controlling for relevant covariates, including age and sex.None of the asymptomatic first-degree relatives of MTLE + HS patients showed evidence of HS on qualitative image assessments. Compared to the healthy controls, the asymptomatic relatives of patients displayed no significant differences in intracranial volume, average hemispheric surface area, or hippocampal volume. Similarly, no significant cerebral cortical thinning was identified in the relatives of patients. This was consistent across the 3 cohorts.Lack of cortical thickness changes in the asymptomatic relatives of patients indicates that the previously characterized MTLE + HS-related cortical thinning is not heritable, and is likely driven by disease-related factors. This finding therefore argues for early and aggressive intervention in patients with medically intractable epilepsy.
View details for DOI 10.1212/WNL.0000000000006834
View details for PubMedID 30587513
Association between carotid atheroma and cerebral cortex structure at age 73 years.
Annals of neurology
2018; 84 (4): 576–87
To examine the relationship between carotid atherosclerosis and cerebral cortical thickness and investigate whether cortical thickness mediates the association between carotid atheroma and relative cognitive decline.We assessed 554 community-dwelling subjects (male/female: 296/258) from the Lothian Birth Cohort 1936 who underwent brain magnetic resonance imaging and carotid Doppler ultrasound studies at age 73 years. The relationship between carotid atherosclerosis markers (internal carotid artery stenosis, intima-media thickness, velocity, pulsatility, and resistivity indexes) and vertex-wide cerebral cortical thickness was examined cross-sectionally, controlling for gender, extensive vascular risk factors (VRFs), and intelligence quotient at age 11 (IQ-11). We also determined the association between carotid stenosis and a composite measure of fluid intelligence at age 73 years. A mediation model was applied to examine whether cortical thickness mediated the relationship between carotid stenosis and cognitive function.A widespread negative association was identified between carotid stenosis (median = 15%) and cerebral cortical thickness at age 73 years, independent of the side of carotid stenosis, other carotid measures, VRFs, and IQ-11. This association increased in an almost dose-response relationship from mild to severe degrees of carotid stenosis, across the anterior and posterior circulation territories. A negative association was also noted between carotid stenosis and fluid intelligence (standardized beta coefficient = -0.151, p = 0.001), which appeared partly (approximately 22%) mediated by carotid stenosis-related thinning of the cerebral cortex.The findings suggest that carotid stenosis represents a marker of processes that accelerate aging of the cerebral cortex and cognition that is in part independent of measurable VRFs. Cortical thinning within the anterior and posterior circulation territories partially mediated the relationship between carotid atheroma and fluid intelligence. Ann Neurol 2018;84:576-587.
View details for DOI 10.1002/ana.25324
View details for PubMedID 30179274
View details for PubMedCentralID PMC6328248
Quantitative magnetic resonance imaging traits as endophenotypes for genetic mapping in epilepsy.
2016; 12: 526–34
Over the last decade, the field of imaging genomics has combined high-throughput genotype data with quantitative magnetic resonance imaging (QMRI) measures to identify genes associated with brain structure, cognition, and several brain-related disorders. Despite its successful application in different psychiatric and neurological disorders, the field has yet to be advanced in epilepsy. In this article we examine the relevance of imaging genomics for future genetic studies in epilepsy from three perspectives. First, we discuss prior genome-wide genetic mapping efforts in epilepsy, considering the possibility that some studies may have been constrained by inherent theoretical and methodological limitations of the genome-wide association study (GWAS) method. Second, we offer a brief overview of the imaging genomics paradigm, from its original inception, to its role in the discovery of important risk genes in a number of brain-related disorders, and its successful application in large-scale multinational research networks. Third, we provide a comprehensive review of past studies that have explored the eligibility of brain QMRI traits as endophenotypes for epilepsy. While the breadth of studies exploring QMRI-derived endophenotypes in epilepsy remains narrow, robust syndrome-specific neuroanatomical QMRI traits have the potential to serve as accessible and relevant intermediate phenotypes for future genetic mapping efforts in epilepsy.
View details for DOI 10.1016/j.nicl.2016.09.005
View details for PubMedID 27672556
View details for PubMedCentralID PMC5030372
Temporal Cortex Morphology in Mesial Temporal Lobe Epilepsy Patients and Their Asymptomatic Siblings.
Cerebral cortex (New York, N.Y. : 1991)
2016; 26 (3): 1234–41
Temporal cortex abnormalities are common in patients with mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE+HS) and believed to be relevant to the underlying mechanisms. In the present study, we set out to determine the familiarity of temporal cortex morphologic alterations in a cohort of MTLE+HS patients and their asymptomatic siblings. A surface-based morphometry (SBM) method was applied to process MRI data acquired from 140 individuals (50 patients with unilateral MTLE+HS, 50 asymptomatic siblings of patients, and 40 healthy controls). Using a region-of-interest approach, alterations in temporal cortex morphology were determined in patients and their asymptomatic siblings by comparing with the controls. Alterations in temporal cortex morphology were identified in MTLE+HS patients ipsilaterally within the anterio-medial regions, including the entorhinal cortex, parahippocampal gyrus, and temporal pole. Subtle but similar pattern of morphology changes with a medium effect size were also noted in the asymptomatic siblings. These localized alterations were related to volume loss that appeared driven by shared contractions in cerebral cortex surface area. These findings indicate that temporal cortex morphologic alterations are common to patients and their asymptomatic siblings and suggest that such localized traits are possibly heritable.
View details for DOI 10.1093/cercor/bhu315
View details for PubMedID 25576532
White matter alterations in patients with MRI-negative temporal lobe epilepsy and their asymptomatic siblings.
2015; 56 (10): 1551–61
The identification of "endophenotypes"-measurable variations along the pathways between genes and distal disease state-may help deconstruct focal epilepsies into more sensitive phenomena and improve future efforts to map the genetic underpinnings of the disorder. In this study, we set out to determine if diffusion tensor imaging (DTI)-inferred white matter (WM) alterations represent a suitable structural endophenotype for focal epilepsy.We recruited 25 patients with sporadic mesial temporal lobe epilepsy (MTLE) with normal magnetic resonance imaging (MRI) findings, 25 of their gender-matched, asymptomatic siblings, and 60 control subjects. Whole-brain, voxelwise statistics were conducted to identify regions of microstructural degeneration in patients with MTLE and/or their asymptomatic siblings. WM tracts exhibiting evidence of microstructural disruption were then reconstructed using deterministic tractography. Diffusion metrics including fractional anisotropy (FA) and mean diffusivity (MD) were compared across groups using a series of one-way multivariate analyses of covariance (MANCOVAs).Voxelwise statistics revealed significant FA reductions in the corpus callosum (CC), bilateral superior longitudinal fasciculi (SLF), bilateral inferior longitudinal fasciculi (ILF), and left corticospinal tract (CST) in MTLE patients only. MD increases were observed in MTLE patients and their asymptomatic siblings in the left SLF and left CST. Deterministic tractography supported the voxelwise results, revealing significant FA alterations in the left SLF and CST in patients only and significant MD alterations in MTLE patients and their unaffected siblings. The diffusion scalars of MTLE patients and their asymptomatic siblings were highly correlated in the SLF and CST ipsilateral to patients' sides of seizure onset.These findings confirm the presence of microstructural WM alterations in patients with MRI-negative MTLE and provide preliminary support for a diffusion-based endophenotype in the disorder. Further studies of narrow-sense heritability in larger cohorts of first-degree relatives of MTLE patients are required to confirm these results.
View details for DOI 10.1111/epi.13103
View details for PubMedID 26249101
The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data
BRAIN IMAGING AND BEHAVIOR
2014; 8 (2): 153-182
The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
View details for DOI 10.1007/s11682-013-9269-5
View details for Web of Science ID 000335765700003
View details for PubMedID 24399358
Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A.
Brain : a journal of neurology
2013; 136 (Pt 10): 3140–50
Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10(-9), odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures.
View details for DOI 10.1093/brain/awt233
View details for PubMedID 24014518
View details for PubMedCentralID PMC3784283
Regional increase of cerebral cortex thickness in juvenile myoclonic epilepsy.
2013; 54 (9): e138–41
The goal of this study was to characterize cerebral cortex thickness patterns in juvenile myoclonic epilepsy (JME). Surface-based morphometry (SBM) was applied to process brain magnetic resonance images acquired from 24 patients with JME and 40 healthy controls and quantify cerebral cortex thickness. Differences in cortical thickness between patients and controls were determined using generalized linear model (covariates: age and gender). In patients with JME, thickness increase was detected bilaterally within localized regions in the orbitofrontal and mesial frontal cortices. Such thickness patterns coexisted with significant bilateral reduction in thalamic volume. These findings confirm that the underlying mechanisms in JME are related to aberrant corticothalamic structure and indicate that frontal cortex abnormalities are possibly linked to regional increase in cerebral cortical thickness.
View details for DOI 10.1111/epi.12330
View details for PubMedID 23944956
Heritability of subcortical volumetric traits in mesial temporal lobe epilepsy.
2013; 8 (4): e61880
We aimed to 1) determine if subcortical volume deficits are common to mesial temporal lobe epilepsy (MTLE) patients and their unaffected siblings 2) assess the suitability of subcortical volumetric traits as endophenotypes for MTLE.MRI-based volume measurements of the hippocampus, amygdala, thalamus, caudate, putamen and pallidium were generated using an automated brain reconstruction method (FreeSurfer) for 101 unrelated 'sporadic' MTLE patients [70 with hippocampal sclerosis (MTLE+HS), 31 with MRI-negative TLE], 83 unaffected full siblings of patients and 86 healthy control subjects. Changes in the volume of subcortical structures in patients and their unaffected siblings were determined by comparison with healthy controls. Narrow sense heritability was estimated ipsilateral and contralateral to the side of seizure activity.MTLE+HS patients displayed significant volume deficits across the hippocampus, amygdala and thalamus ipsilaterally. In addition, volume loss was detected in the putamen bilaterally. These volume deficits were not present in the unaffected siblings of MTLE+HS patients. Ipsilaterally, the heritability estimates were dramatically reduced for the volume of the hippocampus, thalamus and putamen but remained in the expected range for the amygdala. MRI-negative TLE patients and their unaffected siblings showed no significant volume changes across the same structures and heritability estimates were comparable with calculations from a healthy population.The findings indicate that volume deficits for many subcortical structures in 'sporadic' MTLE+HS are not heritable and likely related to acquired factors. Therefore, they do not represent suitable endophenotypes for MTLE+HS. The findings also support the view that, at a neuroanatomical level, MTLE+HS and MRI-negative TLE represent two distinct forms of MTLE.
View details for DOI 10.1371/journal.pone.0061880
View details for PubMedID 23626743
View details for PubMedCentralID PMC3633933
MRI-based brain structure volumes in temporal lobe epilepsy patients and their unaffected siblings: a preliminary study.
Journal of neuroimaging : official journal of the American Society of Neuroimaging
2013; 23 (1): 64–70
Investigating the heritability of brain structure may be useful in simplifying complicated genetic studies in temporal lobe epilepsy (TLE). A preliminary study is presented to determine if volume deficits of candidate brain structures present at a higher rate in unaffected siblings than controls subjects.T1-weighted MR images was acquired for 28 TLE patients, a same-sex unaffected sibling of 12 of these and 28 normal controls. Selected brain structure volumes were measured using an automated whole brain segmentation technique. Candidate brain structure endophenotypes were determined and group differences were investigated between (1) controls and patients and (2) controls and siblings. ICC's were used to measure the quantitative volumetric association within each sibling pair.TLE patients demonstrated a significantly lower cerebral white matter, bilateral hippocampus, thalamus, and left entorhinal cortex volumes when compared with controls. A significant deficit in cerebral white matter (CWM) was common to patient and nonaffected siblings when compared with controls. Furthermore, a significant correlation was revealed between patients and siblings in CWM and bilateral thalamus.The findings suggest an overlap in the neurodevelopmental genes responsible for both brain structure and the expression of the disease. Further work is ongoing to confirm these findings.
View details for DOI 10.1111/j.1552-6569.2012.00736.x
View details for PubMedID 22928655
A cross-sectional MRI study of brain regional atrophy and clinical characteristics of temporal lobe epilepsy with hippocampal sclerosis.
2012; 99 (1-2): 156–66
Applying a cross-sectional design, we set out to further characterize the significance of extrahippocampal brain atrophy in a large sample of 'sporadic' mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS). By evaluating the influence of epilepsy chronicity on structural atrophy, this work represents an important step towards the characterization of MRI-based volumetric measurements as genetic endophenotypes for this condition.Using an automated brain segmentation technique, MRI-based volume measurements of several brain regions were compared between 75 patients with 'sporadic' MTLE+HS and 50 healthy controls. Applying linear regression models, we examined the relationship between structural atrophy and important clinical features of MTLE+HS, including disease duration, lifetime number of partial and generalized seizures, and history of initial precipitating insults (IPIs).Significant volume loss was detected in ipsilateral hippocampus, amygdala, thalamus, and cerebral white matter (WM). In addition, contralateral hippocampal and bilateral cerebellar grey matter (GM) volume loss was observed in left MTLE+HS patients. Hippocampal, amygdalar, and cerebral WM volume loss correlated with duration of epilepsy. This correlation was stronger in patients with prior IPIs history. Further, cerebral WM, cerebellar GM, and contralateral hippocampal volume loss correlated with lifetime number of generalized seizures.Our findings confirm that multiple brain regions beyond the hippocampus are involved in the pathogenesis of MTLE+HS. IPIs are an important factor influencing the rate of regional atrophy but our results also support a role for processes related to epilepsy chronicity. The consequence of epilepsy chronicity on candidate brain regions has important implications on their application as genetic endophenotypes.
View details for DOI 10.1016/j.eplepsyres.2011.11.005
View details for PubMedID 22197033
Widespread cortical morphologic changes in juvenile myoclonic epilepsy: evidence from structural MRI.
2012; 53 (4): 651–58
Atypical morphology of the surface of the cerebral cortex may be related to abnormal cortical folding (gyrification) and therefore may indicate underlying malformations of cortical development (MCDs). Using magnetic resonance imaging (MRI)-based analysis, we examined cortical morphology in patients with juvenile myoclonic epilepsy (JME).MRI data was collected for 24 patients with JME and 40 demographically matched healthy controls. FreeSurfer, an automated cortical surface reconstruction method, was applied to compare cortical morphology between patients and controls. Areas of anomalous cortical morphology were defined as regions of interest (ROIs) to contrast regional cortical parameters, such as surface area, average thickness, and mean curvature between patients and controls.In patients with JME, changes to cortical morphology were detected in several regions. In the left hemisphere, these were in insular and cingulate cortices, occipital pole, and middle temporal and fusiform gyri. In the right hemisphere, changes were detected in insular cortex, inferior temporal gyrus, and precuneus. Further analysis of ROIs revealed that these changes are related to differences in surface area rather than average cortical thickness. In addition, mean curvature abnormalities were detected in the insula bilaterally, the left cingulate cortex, and right inferior temporal gyrus.The morphologic findings in this study suggest that structural abnormalities in JME extend beyond mesial frontal lobe regions of the brain. These may be indicative of areas of subtle cortical folding abnormality related to early disruption of cortical development.
View details for DOI 10.1111/j.1528-1167.2012.03413.x
View details for PubMedID 22360759
Asymmetric cortical surface area and morphology changes in mesial temporal lobe epilepsy with hippocampal sclerosis.
2012; 53 (6): 995–1003
To date, magnetic resonance imaging (MRI)-based studies of the cerebral cortex in mesial temporal lobe epilepsy (MTLE) have focused primarily on investigating cortical volume and thickness. However, volume is a composite of surface area and thickness, each reflecting distinct neurobiologic and genetic processes. The goal of this study was to investigate cerebral cortex (1) surface area, (2) surface geometric distortion, and (3) thickness in MTLE with hippocampal sclerosis (HS).Seventy patients with "sporadic" unilateral MTLE + HS and 40 healthy controls underwent T(1) -weighted MRI. Processing MR images using an automated cortical surface reconstruction method (FreeSurfer), we quantified cortical surface area, surface geometric distortion (metric distortion), and thickness at each vertex across the entire cortex. Differences between patients and controls were determined using generalized linear models. Separate linear regression models were employed to assess the relationship between cortical surface area and hippocampal volume as well as a series of important clinical features of the condition.We detected an asymmetric reduction in cortical surface area, predominantly in ipsilateral mesial and anterior temporal lobe subregions, of patients with MTLE + HS. Changes in surface geometric features were also evident and closely mirrored surface area patterns. In contrast, cortical thinning appeared dispersed across the cortex bilaterally. The regression models revealed that ipsilateral hippocampal volume was a significant predictor of temporal lobe surface area changes.Our findings indicate that contraction in surface area, rather than cortical thinning, explains ipsilateral mesial and anterior temporal lobe atrophy in patients with MTLE with HS. Furthermore, the alterations in surface geometry indicate folding abnormality involving the same regions. Cortical surface changes may represent sequelae of the disease or deviant cortical development.
View details for DOI 10.1111/j.1528-1167.2012.03457.x
View details for PubMedID 22510097
HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.
The New England journal of medicine
2011; 364 (12): 1134–43
Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B*1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) in the Han Chinese and other Asian populations but not in European populations.We performed a genomewide association study of samples obtained from 22 subjects with carbamazepine-induced hypersensitivity syndrome, 43 subjects with carbamazepine-induced maculopapular exanthema, and 3987 control subjects, all of European descent. We tested for an association between disease and HLA alleles through proxy single-nucleotide polymorphisms and imputation, confirming associations by high-resolution sequence-based HLA typing. We replicated the associations in samples from 145 subjects with carbamazepine-induced hypersensitivity reactions.The HLA-A*3101 allele, which has a prevalence of 2 to 5% in Northern European populations, was significantly associated with the hypersensitivity syndrome (P=3.5×10(-8)). An independent genomewide association study of samples from subjects with maculopapular exanthema also showed an association with the HLA-A*3101 allele (P=1.1×10(-6)). Follow-up genotyping confirmed the variant as a risk factor for the hypersensitivity syndrome (odds ratio, 12.41; 95% confidence interval [CI], 1.27 to 121.03), maculopapular exanthema (odds ratio, 8.33; 95% CI, 3.59 to 19.36), and SJS-TEN (odds ratio, 25.93; 95% CI, 4.93 to 116.18).The presence of the HLA-A*3101 allele was associated with carbamazepine-induced hypersensitivity reactions among subjects of Northern European ancestry. The presence of the allele increased the risk from 5.0% to 26.0%, whereas its absence reduced the risk from 5.0% to 3.8%. (Funded by the U.K. Department of Health and others.).
View details for DOI 10.1056/NEJMoa1013297
View details for PubMedID 21428769
View details for PubMedCentralID PMC3113609
Pharmacogenomics and epilepsy: the road ahead.
2011; 12 (10): 1429–47
Epilepsy is one of the most common, serious neurological disorders, affecting an estimated 50 million people worldwide. The condition is typically treated using antiepileptic drugs of which there are 16 in widespread use. However, there are many different syndrome and seizure types within epilepsy and information guiding clinicians on the most effective drug and dose for individual patients is lacking. Further, all of the antiepileptic drugs have associated adverse reactions, some of which are severe and life-threatening. Here, we review the pharmacogenomic work to date in the context of these issues and comment on key aspects of study design that are required to speed up the identification of clinically relevant genetic factors.
View details for DOI 10.2217/pgs.11.85
View details for PubMedID 22008048
Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study.
Brain : a journal of neurology
2010; 133 (Pt 7): 2136–47
Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many other common diseases for which genetic association-studies have successfully revealed common variants associated with disease risk, the role of common variation in partial epilepsies has not yet been explored in a well-powered study. We undertook a genome-wide association-study to identify common variants which influence risk for epilepsy shared amongst partial epilepsy syndromes, in 3445 patients and 6935 controls of European ancestry. We did not identify any genome-wide significant association. A few single nucleotide polymorphisms may warrant further investigation. We exclude common genetic variants with effect sizes above a modest 1.3 odds ratio for a single variant as contributors to genetic susceptibility shared across the partial epilepsies. We show that, at best, common genetic variation can only have a modest role in predisposition to the partial epilepsies when considered across syndromes in Europeans. The genetic architecture of the partial epilepsies is likely to be very complex, reflecting genotypic and phenotypic heterogeneity. Larger meta-analyses are required to identify variants of smaller effect sizes (odds ratio<1.3) or syndrome-specific variants. Further, our results suggest research efforts should also be directed towards identifying the multiple rare variants likely to account for at least part of the heritability of the partial epilepsies. Data emerging from genome-wide association-studies will be valuable during the next serious challenge of interpreting all the genetic variation emerging from whole-genome sequencing studies.
View details for DOI 10.1093/brain/awq130
View details for PubMedID 20522523
View details for PubMedCentralID PMC2892941