Genetic and Epigenetic Regulation in <i>Lingo-1</i>: Effects on Cognitive Function and White Matter Microstructure in a Case-Control Study for Schizophrenia
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 geneti...
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MDPI AG
2023-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/21/15624 |
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| author | Jessica L. Andrews Andrew Zalesky Shalima Nair Ryan P. Sullivan Melissa J. Green Christos Pantelis Kelly A. Newell Francesca Fernandez |
| author_facet | Jessica L. Andrews Andrew Zalesky Shalima Nair Ryan P. Sullivan Melissa J. Green Christos Pantelis Kelly A. Newell Francesca Fernandez |
| author_sort | Jessica L. Andrews |
| collection | DOAJ |
| description | 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 <i>Lingo-1</i> 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 (<i>p</i> = 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 (<i>p</i> = 0.032) compared to the schizophrenia group. rs3144 genotype was predictive of membership to a subclass of schizophrenia subjects with generalized cognitive deficits (<i>p</i> < 0.05), in addition to having associations with WM integrity (<i>p</i> = 0.018). This is the first study reporting a potential implication of genetic and epigenetic risk factors in <i>Lingo-1</i> 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. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T11:29:01Z |
| publishDate | 2023-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b4d47297b9104fa79d017f7401f046d92023-11-10T15:04:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124211562410.3390/ijms242115624Genetic and Epigenetic Regulation in <i>Lingo-1</i>: Effects on Cognitive Function and White Matter Microstructure in a Case-Control Study for SchizophreniaJessica L. Andrews0Andrew Zalesky1Shalima Nair2Ryan P. Sullivan3Melissa J. Green4Christos Pantelis5Kelly A. Newell6Francesca Fernandez7School of Medical, Indigenous and Health Sciences, and Molecular Horizons, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, AustraliaMelbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Carlton South, VIC 3053, AustraliaEpigenetics Research Program, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, NSW 2010, AustraliaARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, University of Wollongong, Wollongong, NSW 2522, AustraliaSchool of Clinical Medicine, Discipline of Psychiatry and Mental Health, UNSW Sydney, Sydney, NSW 2052, AustraliaMelbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Carlton South, VIC 3053, AustraliaSchool of Medical, Indigenous and Health Sciences, and Molecular Horizons, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, AustraliaSchool of Medical, Indigenous and Health Sciences, and Molecular Horizons, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, AustraliaLeucine-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 <i>Lingo-1</i> 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 (<i>p</i> = 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 (<i>p</i> = 0.032) compared to the schizophrenia group. rs3144 genotype was predictive of membership to a subclass of schizophrenia subjects with generalized cognitive deficits (<i>p</i> < 0.05), in addition to having associations with WM integrity (<i>p</i> = 0.018). This is the first study reporting a potential implication of genetic and epigenetic risk factors in <i>Lingo-1</i> 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.https://www.mdpi.com/1422-0067/24/21/15624Lingo-1 geneschizophreniasingle nucleotide polymorphismmethylationwhite mater integritycognition |
| spellingShingle | Jessica L. Andrews Andrew Zalesky Shalima Nair Ryan P. Sullivan Melissa J. Green Christos Pantelis Kelly A. Newell Francesca Fernandez Genetic and Epigenetic Regulation in <i>Lingo-1</i>: Effects on Cognitive Function and White Matter Microstructure in a Case-Control Study for Schizophrenia International Journal of Molecular Sciences Lingo-1 gene schizophrenia single nucleotide polymorphism methylation white mater integrity cognition |
| title | Genetic and Epigenetic Regulation in <i>Lingo-1</i>: Effects on Cognitive Function and White Matter Microstructure in a Case-Control Study for Schizophrenia |
| title_full | Genetic and Epigenetic Regulation in <i>Lingo-1</i>: Effects on Cognitive Function and White Matter Microstructure in a Case-Control Study for Schizophrenia |
| title_fullStr | Genetic and Epigenetic Regulation in <i>Lingo-1</i>: Effects on Cognitive Function and White Matter Microstructure in a Case-Control Study for Schizophrenia |
| title_full_unstemmed | Genetic and Epigenetic Regulation in <i>Lingo-1</i>: Effects on Cognitive Function and White Matter Microstructure in a Case-Control Study for Schizophrenia |
| title_short | Genetic and Epigenetic Regulation in <i>Lingo-1</i>: Effects on Cognitive Function and White Matter Microstructure in a Case-Control Study for Schizophrenia |
| title_sort | genetic and epigenetic regulation in i lingo 1 i effects on cognitive function and white matter microstructure in a case control study for schizophrenia |
| topic | Lingo-1 gene schizophrenia single nucleotide polymorphism methylation white mater integrity cognition |
| url | https://www.mdpi.com/1422-0067/24/21/15624 |
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