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

Ebrahim Mahmoudi; Joshua R Atkins; Yann Quidé; William R Reay; Heath M Cairns; Chantel Fitzsimmons; Vaughan J Carr; Melissa J Green; Murray J Cairns

doi:10.1093/schbul/sbaa123

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

Schizophr Bull. 2021 Mar 16;47(2):495-504. doi: 10.1093/schbul/sbaa123.

Authors

Ebrahim Mahmoudi^{1

2

3}, Joshua R Atkins^{1

2

3}, Yann Quidé^{4

5}, William R Reay^{1

2

3}, Heath M Cairns^{1

2

3}, Chantel Fitzsimmons^{1

2

3}, Vaughan J Carr^{4

5

6}, Melissa J Green^{4

5}, Murray J Cairns^{1

2

3}

Affiliations

¹ School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
² Centre for Brain and Mental Health Research, University of Newcastle, Callaghan, New South Wales, Australia.
³ Hunter Medical Research Institute, New South Wales, New Lambton, Australia.
⁴ School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.
⁵ Neuroscience Research Australia, Randwick, New South Wales, Australia.
⁶ Department of Psychiatry, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.

Abstract

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 (VNTR4) 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 VNTR4 may impact neuroanatomical development that may, in turn, influence the expression of more severe cognitive symptoms in patients with schizophrenia.

Keywords: MIR137 VNTR; cognitive deficit; genome sequencing; neuroanatomy; schizophrenia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cerebral Cortex / diagnostic imaging
Cerebral Cortex / pathology*
Cognitive Dysfunction* / diagnostic imaging
Cognitive Dysfunction* / etiology
Cognitive Dysfunction* / genetics
Cognitive Dysfunction* / pathology
Female
Humans
Magnetic Resonance Imaging
Male
MicroRNAs / genetics*
Middle Aged
Minisatellite Repeats / genetics*
Schizophrenia* / complications
Schizophrenia* / diagnostic imaging
Schizophrenia* / genetics
Schizophrenia* / pathology
Whole Genome Sequencing

Substances

MIRN137 microRNA, human
MicroRNAs