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The MIR137 VNTR rs58335419 Is Associated With Cognitive Impairment in Schizophrenia and Altered Cortical Morphology

Genome-wide association studies (GWAS) of schizophrenia have strongly implicated a risk locus in close proximity to the gene for miR-137. While there are candidate single-nucleotide polymorphisms (SNPs) with functional implications for the microRNA’s expression encompassed by the common haplotype ta...

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Autores principales: Mahmoudi, Ebrahim, Atkins, Joshua R, Quidé, Yann, Reay, William R, Cairns, Heath M, Fitzsimmons, Chantel, Carr, Vaughan J, Green, Melissa J, Cairns, Murray J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370045/
https://www.ncbi.nlm.nih.gov/pubmed/32910167
http://dx.doi.org/10.1093/schbul/sbaa123
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author Mahmoudi, Ebrahim
Atkins, Joshua R
Quidé, Yann
Reay, William R
Cairns, Heath M
Fitzsimmons, Chantel
Carr, Vaughan J
Green, Melissa J
Cairns, Murray J
author_facet Mahmoudi, Ebrahim
Atkins, Joshua R
Quidé, Yann
Reay, William R
Cairns, Heath M
Fitzsimmons, Chantel
Carr, Vaughan J
Green, Melissa J
Cairns, Murray J
author_sort Mahmoudi, Ebrahim
collection PubMed
description Genome-wide association studies (GWAS) of schizophrenia have strongly implicated a risk locus in close proximity to the gene for miR-137. While there are candidate single-nucleotide polymorphisms (SNPs) with functional implications for the microRNA’s expression encompassed by the common haplotype tagged by rs1625579, there are likely to be others, such as the variable number tandem repeat (VNTR) variant rs58335419, that have no proxy on the SNP genotyping platforms used in GWAS to date. Using whole-genome sequencing data from schizophrenia patients (n = 299) and healthy controls (n = 131), we observed that the MIR137 4-repeats VNTR (VNTR(4)) variant was enriched in a cognitive deficit subtype of schizophrenia and associated with altered brain morphology, including thicker left inferior temporal gyrus and deeper right postcentral sulcus. These findings suggest that the MIR137 VNTR(4) may impact neuroanatomical development that may, in turn, influence the expression of more severe cognitive symptoms in patients with schizophrenia.
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spelling pubmed-83700452021-08-18 The MIR137 VNTR rs58335419 Is Associated With Cognitive Impairment in Schizophrenia and Altered Cortical Morphology Mahmoudi, Ebrahim Atkins, Joshua R Quidé, Yann Reay, William R Cairns, Heath M Fitzsimmons, Chantel Carr, Vaughan J Green, Melissa J Cairns, Murray J Schizophr Bull Regular Articles Genome-wide association studies (GWAS) of schizophrenia have strongly implicated a risk locus in close proximity to the gene for miR-137. While there are candidate single-nucleotide polymorphisms (SNPs) with functional implications for the microRNA’s expression encompassed by the common haplotype tagged by rs1625579, there are likely to be others, such as the variable number tandem repeat (VNTR) variant rs58335419, that have no proxy on the SNP genotyping platforms used in GWAS to date. Using whole-genome sequencing data from schizophrenia patients (n = 299) and healthy controls (n = 131), we observed that the MIR137 4-repeats VNTR (VNTR(4)) variant was enriched in a cognitive deficit subtype of schizophrenia and associated with altered brain morphology, including thicker left inferior temporal gyrus and deeper right postcentral sulcus. These findings suggest that the MIR137 VNTR(4) may impact neuroanatomical development that may, in turn, influence the expression of more severe cognitive symptoms in patients with schizophrenia. Oxford University Press 2020-09-10 /pmc/articles/PMC8370045/ /pubmed/32910167 http://dx.doi.org/10.1093/schbul/sbaa123 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Regular Articles
Mahmoudi, Ebrahim
Atkins, Joshua R
Quidé, Yann
Reay, William R
Cairns, Heath M
Fitzsimmons, Chantel
Carr, Vaughan J
Green, Melissa J
Cairns, Murray J
The MIR137 VNTR rs58335419 Is Associated With Cognitive Impairment in Schizophrenia and Altered Cortical Morphology
title The MIR137 VNTR rs58335419 Is Associated With Cognitive Impairment in Schizophrenia and Altered Cortical Morphology
title_full The MIR137 VNTR rs58335419 Is Associated With Cognitive Impairment in Schizophrenia and Altered Cortical Morphology
title_fullStr The MIR137 VNTR rs58335419 Is Associated With Cognitive Impairment in Schizophrenia and Altered Cortical Morphology
title_full_unstemmed The MIR137 VNTR rs58335419 Is Associated With Cognitive Impairment in Schizophrenia and Altered Cortical Morphology
title_short The MIR137 VNTR rs58335419 Is Associated With Cognitive Impairment in Schizophrenia and Altered Cortical Morphology
title_sort mir137 vntr rs58335419 is associated with cognitive impairment in schizophrenia and altered cortical morphology
topic Regular Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370045/
https://www.ncbi.nlm.nih.gov/pubmed/32910167
http://dx.doi.org/10.1093/schbul/sbaa123
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