Rare GRIN2A Variant Linked to an 87-fold Increase in Schizophrenia Risk — a Rare Single-Gene Effect

Researchers have identified a rare variant in the GRIN2A gene that is associated with roughly an 87-fold increase in schizophrenia risk and smaller increases in risk for other disorders. GRIN2A encodes an NMDA receptor subunit involved in synaptic signaling, giving a plausible biological link to psychiatric symptoms. This finding is a rare example of a single-gene, high-effect variant in psychiatric genetics, but it accounts for only a tiny fraction of schizophrenia cases. Further work is needed to confirm the mechanism and clinical implications.

11:32 PM, 12/03/2025Health

Rare GRIN2A Variant Linked to an 87-fold Increase in Schizophrenia Risk — a Rare Single-Gene Effect

Researchers report that a rare variant in the GRIN2A gene is associated with a dramatically increased risk of schizophrenia, representing one of the few examples in psychiatric genetics where a single genetic change has a very large effect.

What the study found

Carrying this specific GRIN2A variant was associated with an approximately 87-fold higher risk of schizophrenia compared with noncarriers. The same variant also appears to modestly increase risk for some other neuropsychiatric conditions. GRIN2A encodes a subunit of the NMDA receptor, a protein important for synaptic signaling in the brain, so changes to this gene can plausibly affect neural circuitry.

Context: single-gene vs polygenic traits

Most complex traits — including psychiatric disorders such as schizophrenia — are polygenic, influenced by many genes each with small effects. Finding a single variant with a very large effect is unusual and noteworthy, but it does not overturn the broader picture: this GRIN2A variant explains only a tiny fraction of all schizophrenia cases.

Why this matters

The discovery is important for several reasons. It provides a clearer biological handle on how disruption of an NMDA receptor subunit can contribute to severe psychiatric illness, offers a potential target for follow-up laboratory and drug-development studies, and may inform genetic counseling for affected families. However, because the variant is rare, it will not account for most patients with schizophrenia and should not be interpreted as a general diagnostic marker for the disorder.

Caveats and next steps

Further research is needed to confirm causality, determine how the variant alters receptor function, and assess its prevalence across populations. Clinicians and patients should interpret these findings cautiously: a high relative risk for carriers does not imply that schizophrenia is a simple, single-gene disease for the population at large.

Rare GRIN2A Variant Linked to an 87-fold Increase in Schizophrenia Risk — a Rare Single-Gene Effect

Similar Articles

Anxiety Traced to a Tiny Amygdala Circuit — Reversed in Mice by Fixing One Gene

Scientists Pinpoint Amygdala Neurons That Drive Anxiety — Reducing GRIK4 Calms Symptoms in Mice

Documentary Claims Hitler’s DNA Sequenced: Researchers Report PROK2 Mutation and Elevated Psychiatric Polygenic Scores — Experts Urge Caution

Kentucky Researchers Convert Alzheimer’s Risk Gene to Protective Form in Mice — A Promising Proof of Concept

A Dangerous Precedent? DNA Companies Offer Parents the Chance to Choose Embryos by Traits

How NOD2 Mutations Drive Crohn’s: Machine Learning Reveals a Macrophage Switch Failure

Channel 4 Documentary Claims Hitler May Have Had Kallmann Syndrome and Very High Genetic Risk Scores

Hitler's DNA Study Sparks Ethical Debate — What the Genome Can (and Can't) Tell Us

Scientists Find 'Mutation Hotspots' at Gene Start Sites — A Hidden Source of Genetic Change

CTE May Be Driven by Inflammation-Linked DNA Damage in Neurons, Study Finds

Why Some Golden Retrievers Seem Anxious — New Study Points to Shared Genes

Study Finds People with Higher Psychopathy Scores Have ~9% Larger Striatum

Hitler's DNA Study Suggests Kallmann Syndrome — Researchers Warn Against Genetic Determinism

Alzheimer's May Hijack Cellular Clocks — New Study Finds Clock-Controlled Genes Linked to Disease

Scientists Identify Microplastics in Human Brains — Found More Often in Dementia-Linked Tissue

Researchers Identify Microplastics Hidden as 'Glassy Blobs' in Human Brains — Possible Dementia Link Under Investigation

Mayo Clinic Tool Predicts Alzheimer’s Risk Years Before Symptoms — Who’s Most at Risk?

Gut Microbe and Its Metabolite May Trigger an Ozempic‑Like GLP‑1 Response — A Potential Natural Way to Curb Sugar Cravings

Genes, Not Just Screens: Twin Study Finds Only Small Links Between Social Media and Well‑Being

UTHealth Grows Lab 'Mini Brains' from Skin Cells to Uncover Causes of Schizophrenia

Trending