What you carry at this position in your DNA and what research says about it.
Schizophrenia Risk: 7/10 evidence, 53 publications.
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Sample genotype (not yours): A/A
Moderately Higher Risk of Psychosis and Altered Connectivity
Two copies of the A allele are associated with a modest increase in susceptibility to schizophrenia and subtle differences in brain network communication. There is also a documented link to a reduced response to certain antipsychotic medications.
What this genotype means: Approximately 1.2x higher relative risk for schizophrenia; Subtly reduced functional connectivity between key brain regions; Potentially less effective response to certain antipsychotic medications.
Sample genotype (not yours): A/C
Slightly Higher Risk of Psychosis and Altered Connectivity
Carrying one copy of the A allele is linked to a very mild increase in susceptibility to schizophrenia and subtle variations in how brain networks coordinate. General medication response typically remains within the normal range.
What this genotype means: Approximately 1.1x higher relative risk for schizophrenia; Minor variations in prefrontal brain network connectivity; Typical response to standard antipsychotic treatments.
Sample genotype (not yours): C/C
Typical Risk of Psychosis and Standard Brain Connectivity
Two copies of the protective C allele are associated with a baseline risk for schizophrenia and typical patterns of brain network communication. Antipsychotic medication response is expected to be standard.
What this genotype means: Baseline relative risk for schizophrenia and psychosis; Typical structural and functional brain connectivity patterns; Standard response profile to antipsychotic medications.
Gene function and biological role
Gene Function: The ZNF804A gene encodes zinc finger protein 804A, a protein highly active in the developing human brain, particularly in the prefrontal cortex and temporal lobes [1]. This protein acts as a transcription factor, regulating the expression of several other genes critical for neural development, synaptic plasticity, and chemical signaling [2]. Research suggests it plays a pivotal role in maintaining the structural integrity of white matter tracts and modulating functional communication between distant brain regions [3]. Alterations in its expression are thought to influence susceptibility to major psychiatric conditions by subtly shifting early neurodevelopmental trajectories [4].
Variant Impact: The rs1344706 variant is an intronic change within the ZNF804A gene that acts as a cis-regulatory element, directly influencing how the gene is transcribed [5]. Carrying the risk-associated A allele is linked to altered expression levels of ZNF804A during critical windows of fetal brain development [4]. This molecular shift is associated with downstream changes in brain structure, including variations in cortical thickness and reduced white matter tract integrity [6]. It is widely recognized as one of the very first genetic markers to reach genome-wide significance for psychosis and schizophrenia risk in large-scale genetic studies [7].
Key Insight: This variant was the first in genetic history to cross the strict statistical threshold for genome-wide significance in schizophrenia, and it influences how different parts of the brain communicate during complex social tasks.
Location: ZNF804A. Chromosome 2 · 2q32.1 · 184.9 Mb
Estimated prevalence by population
Global 50.4%; European 37.3%; African 84.1%; East Asian 25.2%; South Asian 41.5%; Americas 41.4%; Ashkenazi 41.5%; Finnish 35.5%; Middle Eastern 55.0%; Amish 37.7%.
Estimated AA genotype frequency.
Global 38.5%; European 47.5%; African 15.2%; East Asian 50.0%; South Asian 45.9%; Americas 45.9%; Ashkenazi 45.8%; Finnish 48.2%; Middle Eastern 38.3%; Amish 47.4%.
Estimated AC genotype frequency.
Global 11.2%; European 15.1%; African 0.7%; East Asian 24.9%; South Asian 12.7%; Americas 12.7%; Ashkenazi 12.6%; Finnish 16.4%; Middle Eastern 6.7%; Amish 14.9%.
Estimated CC genotype frequency.
Showing effects for A/A genotype
Neurology & Mental Health
Psychotic Disorders
Schizophrenia. Evidence: 7/10. Source: PMID 18677311. ~1.2x Higher Risk.
Addiction & Reward
Substance Use Risk. Evidence: 6/10. Source: PMID 41057643. Increased Risk.
Neurodevelopmental Traits
Brain Connectivity. Evidence: 4/10. Source: PMID 29527501. Altered Connectivity.
Anxiety & Stress Disorders
Obsessive-Compulsive Disorder. Evidence: 6/10. Source: PMID 36137488. Slightly Increased.
Pharmacogenomics
Antidepressant & Psychiatric Drug Response
Antipsychotic Response. Evidence: 5/10. Source: PMID 21892778. Poorer Response.
Showing effects for A/C genotype
Schizophrenia. Evidence: 7/10. Source: PMID 18677311. ~1.1x Higher Risk.
Substance Use Risk. Evidence: 6/10. Source: PMID 41057643. Slightly Increased.
Antipsychotic Response. Evidence: 5/10. Source: PMID 21892778. Typical Response.
Showing effects for C/C genotype
Schizophrenia. Evidence: 7/10. Source: PMID 18677311. Typical Risk.
Substance Use Risk. Evidence: 6/10. Source: PMID 41057643. Typical Risk.
Brain Connectivity. Evidence: 4/10. Source: PMID 29527501. Typical Connectivity.
Obsessive-Compulsive Disorder. Evidence: 6/10. Source: PMID 36137488. Typical.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Inheriting two copies of the A allele correlates with a roughly 1.2-fold increase in the relative risk of developing schizophrenia and related psychotic disorders [1]. Neuroimaging studies show that this genotype is associated with reduced functional connectivity between the prefrontal cortex and the hippocampus, which are key regions for memory and executive control [2]. White matter microstructural integrity also tends to be lower in carriers of this genetic profile [3]. In clinical settings, individuals with this genotype who require antipsychotic treatment have sometimes demonstrated a less robust response to positive symptom management [4]. Additionally, large-scale genetic analyses link this variant to a slightly higher vulnerability to substance use disorders and obsessive-compulsive tendencies [5]. Despite these statistical associations, the absolute risk of developing any psychiatric condition remains low, as environmental factors and thousands of other genetic variants play a dominant role.
Approximately 1.2x higher relative risk for schizophrenia; Subtly reduced functional connectivity between key brain regions; Potentially less effective response to certain antipsychotic medications.
Sample genotype: AC (Heterozygous)
Carrying a single copy of the A allele is associated with a modest 1.1-fold increase in the relative risk of schizophrenia [1]. Brain imaging research indicates that even a single risk allele can influence the structural and functional wiring of the brain, particularly within the prefrontal-hippocampal network [2]. These subtle differences in neural circuitry may influence cognitive processes such as working memory and social cognition [3]. While the risk allele is also associated with broader psychiatric phenotypes like substance use susceptibility, having only one copy generally preserves a typical response to antipsychotic medications compared to those with two copies [4]. The vast majority of people carrying this common genotype do not develop psychiatric disorders, as the genetic influence of a single variant is exceptionally small compared to overall lifestyle, environment, and polygenic background.
Approximately 1.1x higher relative risk for schizophrenia; Minor variations in prefrontal brain network connectivity; Typical response to standard antipsychotic treatments.
Sample genotype: CC (Homozygous)
Carrying two copies of the C allele represents the baseline genetic profile for this locus, showing no elevated risk for schizophrenia or related psychotic disorders [1]. Brain imaging studies of individuals with this genotype demonstrate typical functional connectivity between the prefrontal cortex and the hippocampus, supporting standard cognitive processing and working memory [2]. White matter tract integrity in key brain networks is generally well-preserved in this group [3]. Furthermore, there is no genetic indication of reduced sensitivity to antipsychotic medications or elevated vulnerability to substance use disorders from this specific variant [4]. Because this genotype avoids the risk-associated expression changes in the ZNF804A gene, it serves as the standard reference point in neurodevelopmental genetics.
Baseline relative risk for schizophrenia and psychosis; Typical structural and functional brain connectivity patterns; Standard response profile to antipsychotic medications.
Variants with shared genetic architecture
rs2514218 · DRD2 Gene · Chr 11 · Mental Health Risk
rs1625579 · MIR137HG Gene · Chr 1 · Schizophrenia Risk
rs4129585 · TSNARE1 Gene · Chr 8 · Schizophrenia Risk
The ZNF804A gene: characterization of a novel neural risk mechanism for the major psychoses.
Identification of loci associated with schizophrenia by genome-wide association and follow-up.
Effect of rs1344706 in the ZNF804A gene on the brain network.
Genome-wide meta-analyses of cross substance use disorders in diverse populations.
Content updated August 2026.
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