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Volume 10
Journal of Neurology & Neurophysiology
ISSN: 2155-9562
Neurology Congress 2019
Vascular Dementia Congress 2019
July 22-24, 2019
JOINT EVENT
conferenceseries
.com
July 22-24, 2019 London, UK
&
12
th
International Conference on
Vascular Dementia
32
nd
European Neurology Congress
Malic enzyme 2 and genetic generalized epilepsy
William C. L. Stewart, Meng Wang
and
David A Greenberg
The Abigail Wexner Research Institute at Nationwide Children’s Hospital, USA
G
enetic generalized epilepsy (GGE) is a highly heritable condition (h
2
=66%) consisting of epileptic syndromes
with overlapping symptoms. Previous studies (both linkage and association) identified malic enzyme 2 (ME2)
as a candidate susceptibility gene for adolescent-onset GGE. To definitively test
ME2’s
influence on GGE, we used
three different approaches. First, we compared a newly recruited GGE cohort with an ethnically matched reference
sample from 1000 genomes, using an efficient test of association (POPFAM+). Second, in a previously collected
data set, we replaced the original controls with ethnically matched reference samples to minimize the confounding
effect of population stratification and we used POPFAM+ in the re-analysis. Third, in a post hoc analysis of healthy
human pre-frontal cortex, we identified single nucleotide polymorphisms (SNPs) influencing ME2 messenger RNA
(mRNA) expression and then, we tested those same SNPs for association with GGE in a large case control cohort.
In the analysis of our newly-recruited GGE Cohort, we found a strong association between an ME2 SNP and GGE
(
p
=0.0006 at rs608781). In the re-analysis of previously collected data, we confirmed the Greenberg
et al.,
(2005)
finding of a GGE associated
ME2
risk haplotype. Finally, in the post hoc ME2 expression analysis, we found evidence
for a possible link between GGE and
ME2
gene expression in human brain. Overall, our research (and the research
of others) provides compelling evidence that ME2 influences adolescent onset GGE susceptibility.
Biography
William C. L. Stewart has completed his PhD in Statistics from the University Washington in 2005, and finished his Postdoctoral studies in the Biostatistics
Department at the University of Michigan in 2008. He is a Principal Investigator at the Abigail Wexner Research Institute of Nationwide Children’s Hospital. He
is an Assistant Professor of Statistics and Pediatrics at Ohio State University. He has published more than 30 papers in peer-review journals and has served on
the Editorial Board of Frontiers in Genetics for nine years.
William.Stewart@nationwidechildrens.orgWilliam C. L. Stewart et al., J Neurol Neurophysiol 2019, Volume 10