Genetic and epigenetic regulation in Lingo-1 : Effects on cognitive function and white matter microstructure in a case-control study for schizophrenia

Journal article

Andrews, Jessica L., Zalesky, Andrew, Nair, Shalima, Sullivan, Ryan P., Green, Melissa J., Pantelis, Christos, Newell, Kelly A. and Fernandez, Francesca. (2023). Genetic and epigenetic regulation in Lingo-1 : Effects on cognitive function and white matter microstructure in a case-control study for schizophrenia. International Journal of Molecular Sciences. 24(21), p. Article 15624. https://doi.org/10.3390/ijms242115624
AuthorsAndrews, Jessica L., Zalesky, Andrew, Nair, Shalima, Sullivan, Ryan P., Green, Melissa J., Pantelis, Christos, Newell, Kelly A. and 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.

KeywordsLingo-1 gene; schizophrenia; single nucleotide polymorphism; methylation; white mater integrity; cognition
Year2023
JournalInternational Journal of Molecular Sciences
Journal citation24 (21), p. Article 15624
PublisherMultidisciplinary Digital Publishing Institute (MDPI AG)
ISSN1422-0067
Digital Object Identifier (DOI)https://doi.org/10.3390/ijms242115624
Open accessPublished as ‘gold’ (paid) open access
Page range1-16
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Open
Output statusPublished
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Online26 Oct 2023
Publication process dates
Accepted22 Oct 2023
Deposited08 Nov 2023
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