Validation of a microRNA target site polymorphism in H3F3B that is potentially associated with a broad schizophrenia phenotype

William Manley, Michael P. Moreau, Marco Azaro, Stephen K. Siecinski, Gillian Davis, Steven Buyske, Veronica Vieland, Anne S. Bassett, Linda Brzustowicz

Research output: Contribution to journalArticle

Abstract

Despite much progress, few genetic findings for schizophrenia have been assessed by functional validation experiments at the molecular level. We previously reported evidence for genetic linkage of broadly defined schizophrenia to chromosome 17q25 in a sample of 24 multiplex families. 2,002 SNPs under this linkage peak were analyzed for evidence of linkage disequilibrium using the posterior probability of linkage (PPL) framework. SNP rs1060120 produced the strongest evidence for association, with a PPLD|L score of 0.21. This SNP is located within the 3’UTR of the histone gene H3F3B and colocalizes with potential gene target miR-616. A custom miRNA target prediction program predicted that the binding of miR-616 to H3F3B transcripts would be altered by the allelic variants of rs1060120. We used dual luciferase assays to experimentally validate this interaction. The rs1060120 A allele significantly reduced luciferase expression, indicating a stronger interaction with miR-616 than the G allele (p = 0.000412). These results provide functional validation that this SNP could alter schizophrenia epigenetic mechanisms thereby contributing to schizophrenia-related disease risk.

Original languageEnglish (US)
Article numbere0194233
JournalPloS one
Volume13
Issue number3
DOIs
StatePublished - Mar 2018

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Polymorphism
Luciferases
MicroRNAs
microRNA
Single Nucleotide Polymorphism
Schizophrenia
Genes
genetic polymorphism
linkage (genetics)
Phenotype
phenotype
luciferase
Chromosomes
Histones
Assays
Alleles
Association reactions
alleles
Genetic Linkage
Linkage Disequilibrium

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Manley, William ; Moreau, Michael P. ; Azaro, Marco ; Siecinski, Stephen K. ; Davis, Gillian ; Buyske, Steven ; Vieland, Veronica ; Bassett, Anne S. ; Brzustowicz, Linda. / Validation of a microRNA target site polymorphism in H3F3B that is potentially associated with a broad schizophrenia phenotype. In: PloS one. 2018 ; Vol. 13, No. 3.
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Validation of a microRNA target site polymorphism in H3F3B that is potentially associated with a broad schizophrenia phenotype. / Manley, William; Moreau, Michael P.; Azaro, Marco; Siecinski, Stephen K.; Davis, Gillian; Buyske, Steven; Vieland, Veronica; Bassett, Anne S.; Brzustowicz, Linda.

In: PloS one, Vol. 13, No. 3, e0194233, 03.2018.

Research output: Contribution to journalArticle

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