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Genetic and epigenetic regulation in Lingo-1 : Effects on cognitive function and white matter microstructure in a case-control study for schizophrenia
Andrews, Jessica L. Zalesky, Andrew Nair, Shalima Sullivan, Ryan P. Green, Melissa J. Pantelis, Christos Newell, Kelly A. Fernandez, Francesca
Andrews, Jessica L.
Zalesky, Andrew
Nair, Shalima
Sullivan, Ryan P.
Green, Melissa J.
Pantelis, Christos
Newell, Kelly A.
Fernandez, Francesca
Abstract
Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) plays a vital role in a large number of neuronal processes underlying learning and memory, which are known to be disrupted in schizophrenia. However, Lingo-1 has never been examined in the context of schizophrenia. The genetic association of a single-nucleotide polymorphism (SNP, rs3144) and methylation (CpG sites) in the Lingo-1 3′-UTR region was examined, with the testing of cognitive dysfunction and white matter (WM) integrity in a schizophrenia case-control cohort (n = 268/group). A large subset of subjects (97 control and 161 schizophrenia subjects) underwent structural magnetic resonance imaging (MRI) brain scans to assess WM integrity. Frequency of the rs3144 minor allele was overrepresented in the schizophrenia population (p = 0.03), with an odds ratio of 1.39 (95% CI 1.016–1.901). CpG sites surrounding rs3144 were hypermethylated in the control population (p = 0.032) compared to the schizophrenia group. rs3144 genotype was predictive of membership to a subclass of schizophrenia subjects with generalized cognitive deficits (p < 0.05), in addition to having associations with WM integrity (p = 0.018). This is the first study reporting a potential implication of genetic and epigenetic risk factors in Lingo-1 in schizophrenia. Both of these genetic and epigenetic alterations may also have associations with cognitive dysfunction and WM integrity in the context of the schizophrenia pathophysiology.
Keywords
Lingo-1 gene, schizophrenia, single nucleotide polymorphism, methylation, white mater integrity, cognition
Date
2023
Type
Journal article
Journal
International Journal of Molecular Sciences
Book
Volume
24
Issue
21
Page Range
1-16
Article Number
Article 15624
ACU Department
School of Behavioural and Health Sciences
Faculty of Health Sciences
Faculty of Health Sciences
Relation URI
Source URL
Event URL
Open Access Status
Published as ‘gold’ (paid) open access
License
CC BY 4.0
File Access
Open