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
Authors | Andrews, Jessica L., Zalesky, Andrew, Nair, Shalima, Sullivan, Ryan P., Green, Melissa J., Pantelis, Christos, Newell, Kelly A. and Fernandez, Francesca |
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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 |
Year | 2023 |
Journal | International Journal of Molecular Sciences |
Journal citation | 24 (21), p. Article 15624 |
Publisher | Multidisciplinary Digital Publishing Institute (MDPI AG) |
ISSN | 1422-0067 |
Digital Object Identifier (DOI) | https://doi.org/10.3390/ijms242115624 |
Open access | Published as ‘gold’ (paid) open access |
Page range | 1-16 |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication dates | |
Online | 26 Oct 2023 |
Publication process dates | |
Accepted | 22 Oct 2023 |
Deposited | 08 Nov 2023 |
https://acuresearchbank.acu.edu.au/item/8zy76/genetic-and-epigenetic-regulation-in-lingo-1-effects-on-cognitive-function-and-white-matter-microstructure-in-a-case-control-study-for-schizophrenia
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Publisher's version
OA_Andrews_2023_Genetic_and_epigenetic_regulation_in_Lingo.pdf | |
License: CC BY 4.0 | |
File access level: Open |
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