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Glycobiology and schizophrenia: a biological hypothesis emerging from genomic research.

ABSTRACT: Advances in genomics are opening new windows into the biology of schizophrenia. Though common variants individually have small effects on disease risk, GWAS provide a powerful opportunity to explore pathways and mechanisms contributing to pathophysiology. Here, we highlight an underappreciated biological theme emerging from GWAS: the role of glycosylation in schizophrenia. The strongest coding variant in schizophrenia GWAS is a missense mutation in the manganese transporter SLC39A8, which is associated with altered glycosylation patterns in humans. Furthermore, variants near several genes encoding glycosylation enzymes are unambiguously associated with schizophrenia: FUT9, MAN2A1, TMTC1, GALNT10, and B3GAT1. Here, we summarize the known biological functions, target substrates, and expression patterns of these enzymes as a primer for future studies. We also highlight a subset of schizophrenia-associated proteins critically modified by glycosylation including glutamate receptors, voltage-gated calcium channels, the dopamine D2 receptor, and complement glycoproteins. We hypothesize that common genetic variants alter brain glycosylation and play a fundamental role in the development of schizophrenia. Leveraging these findings will advance our mechanistic understanding of disease and may provide novel avenues for treatment development.

SUBMITTER: Mealer RG

PROVIDER: S-EPMC8081046 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Glycobiology and schizophrenia: a biological hypothesis emerging from genomic research.

Mealer Robert G RG Williams Sarah E SE Daly Mark J MJ Scolnick Edward M EM Cummings Richard D RD Smoller Jordan W JW

Molecular psychiatry 20200506 12

Advances in genomics are opening new windows into the biology of schizophrenia. Though common variants individually have small effects on disease risk, GWAS provide a powerful opportunity to explore pathways and mechanisms contributing to pathophysiology. Here, we highlight an underappreciated biological theme emerging from GWAS: the role of glycosylation in schizophrenia. The strongest coding variant in schizophrenia GWAS is a missense mutation in the manganese transporter SLC39A8, which is ass ...[more]

PMID: 32377000

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Glycobiology and schizophrenia: a biological hypothesis emerging from genomic research.

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Glycobiology and schizophrenia: a biological hypothesis emerging from genomic research.

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