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. 2024 Nov 8;33(22):1939-1947.
doi: 10.1093/hmg/ddae130.

Schizophrenia risk-associated SNPs affect expression of microRNA 137 host gene: a postmortem study

Ningping Feng  1 , Ajeet Mandal  1 , Ananya Jambhale  1 , Pranav Narnur  1 , Gang Chen  2 , Nirmala Akula  3 , Robin Kramer  1 , Bhaskar Kolachana  1 , Qing Xu  1 , Francis J McMahon  3 , Barbara K Lipska  1 , Pavan K Auluck  1 , Stefano Marenco  1
Affiliations

Schizophrenia risk-associated SNPs affect expression of microRNA 137 host gene: a postmortem study

Ningping Feng et al. Hum Mol Genet. .

Abstract

Common variants in the MicroRNA 137 host gene MIR137HG and its adjacent gene DPYD have been associated with schizophrenia risk and the latest Psychiatric Genomics Consortium (PGC). Genome-Wide Association Study on schizophrenia has confirmed and extended these findings. To elucidate the association of schizophrenia risk-associated SNPs in this genomic region, we examined the expression of both mature and immature transcripts of the miR-137 host gene (MIR137HG) in the dorsolateral prefrontal cortex (DLPFC) and subgenual anterior cingulate cortex (sgACC) of postmortem brain samples of donors with schizophrenia and psychiatrically-unaffected controls using qPCR and RNA-Seq approaches. No differential expression of miR-137, MIR137HG, or its transcripts was observed. Two schizophrenia risk-associated SNPs identified in the PGC study, rs11165917 (DLPFC: P = 2.0e-16; sgACC: P = 6.4e-10) and rs4274102 (DLPFC: P = 0.036; sgACC: P = 0.002), were associated with expression of the MIR137HG long non-coding RNA transcript MIR137HG-203 (ENST00000602672.2) in individuals of European ancestry. Carriers of the minor (risk) allele of rs11165917 had significantly lower expression of MIR137HG-203 compared with those carrying the major allele. However, we were unable to validate this result by short-read sequencing of RNA extracted from DLPFC or sgACC tissue. This finding suggests that immature transcripts of MIR137HG may contribute to genetic risk for schizophrenia.

Keywords: MIR137; eQTL; long-non-coding RNA; postmortem; schizophrenia.

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Figures

Figure 1
Figure 1
MIR137HG transcripts annotated at Ensemble Genome Browser and confirmed in this study. (A) Genomic region of MIR137HG and the transcripts annotated at Ensemble Genome Browser (https://useast.ensembl.org/Homo_sapiens/Info/Index, Jan. 2022, GRch38.p13). (B) MIR137HG transcripts confirmed by RT-PCR in this study. Exons (boxes) and introns (lines) are not drawn to scale.
Figure 2
Figure 2
MIR137HG and its adjacent genomic region. A screenshot of the DPYD_ RP11-490G2.2_MIR137HG region at UCSC Genome Browser on human (https://genome.ucsc.edu/index.html, GRCh38/hg38) showing transcripts MIR137HG-203 and MIR137HG-202 and seven PGC3 SNPs (displayed using a custom track).
Figure 3
Figure 3
Box plots and ANCOVA results for the expression of MIR137HG-203 between genotypes of rs11165917 and rs4274102, respectively, in DLPFC and sgACC by qPCR. The subjects were grouped in SCZ only, control only and all subjects (including SCZ, control and other diagnoses) separately. Only the ANCOVA p values from all subjects were presented on the figures: (A) Relative expression of MIR137HG-203 on rs11165917 in DLPFC by qPCR. (B) Relative expression of MIR137HG-203 on rs11165917 in sgACC by qPCR. (C) Relative expression of MIR137HG-203 on rs4274102 in DLPFC by qPCR. (D) Relative expression of MIR137HG-203 on rs4274102 in sgACC by qPCR.
See this image and copyright information in PMC

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