What you carry at this position in your DNA and what research says about it.
Mental Health Risk: 9/10 evidence, 32 publications.
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Sample genotype (not yours): A/A
Typical Risk of Psychiatric Conditions
Carrying two copies of the A allele is associated with baseline susceptibility to mood and psychiatric conditions. This genotype allows for typical processing of brain-derived neurotrophic factor.
What this genotype means: Typical BDNF maturation; Baseline risk of psychiatric conditions; Typical sleep patterns.
Sample genotype (not yours): G/A
Slightly Elevated Risk of Psychiatric Conditions
Carrying one copy of the G allele is linked to a slight increase in the risk of developing mood and psychiatric conditions. This allele reduces the maturation of a key brain-growth protein.
What this genotype means: Slightly reduced BDNF maturation; Slightly higher risk of mood conditions; Increased susceptibility to insomnia.
Sample genotype (not yours): G/G
Elevated Risk of Psychiatric Conditions
Carrying two copies of the G allele is associated with the lowest levels of mature BDNF, leading to an increased risk of psychiatric and mood conditions.
What this genotype means: Reduced BDNF maturation; Elevated risk of psychiatric conditions; Higher likelihood of insomnia.
Gene function and biological role
Gene Function: The FES gene region, which overlaps with the regulatory boundaries of the neighboring FURIN gene, plays a critical role in brain development and synaptic plasticity. This genomic locus is highly active in the central nervous system, where it influences how neurons grow and communicate [1]. Specifically, the region regulates the production of the FURIN enzyme, which is responsible for cutting precursor proteins into their active forms [2]. One of the most vital proteins processed by this enzyme is brain-derived neurotrophic factor, or BDNF, which supports brain cell survival and learning [1]. Consequently, genetic variations in this area can have widespread effects on neurodevelopment and emotional regulation.
Variant Impact: The rs4702 variant is a single-nucleotide change located in the 3 prime untranslated region of the genetic sequence. This specific region acts as a regulatory landing pad where small molecules called microRNAs bind to control how much protein is produced. The G allele creates a highly compatible binding site for a specific microRNA known as miR-338-3p, which leads to the downregulation of FURIN expression [1]. Because FURIN levels drop, the brain is less efficient at converting precursor BDNF into its active, mature form [1]. Conversely, the protective A allele prevents this microRNA from binding efficiently, allowing typical levels of FURIN and mature BDNF to be maintained [1].
Key Insight: The risk allele at this locus acts like a genetic dimmer switch, allowing a specific microRNA to bind and suppress a key enzyme, which ultimately reduces the maturation of the brain-growth protein BDNF.
Location: FURIN. Chromosome 15 · 15q26.1 · 90.9 Mb
Estimated prevalence by population
Global 15.0%; European 20.0%; African 1.3%; East Asian 23.3%; South Asian 24.9%; Americas 16.3%; Ashkenazi 21.0%; Finnish 22.9%; Middle Eastern 25.0%; Amish 13.6%.
Estimated GG genotype frequency.
Global 41.3%; European 49.4%; African 20.3%; East Asian 49.9%; South Asian 50.0%; Americas 48.1%; Ashkenazi 49.7%; Finnish 49.9%; Middle Eastern 50.0%; Amish 46.6%.
Estimated GA genotype frequency.
Global 43.7%; European 30.6%; African 78.4%; East Asian 26.7%; South Asian 25.1%; Americas 35.6%; Ashkenazi 29.3%; Finnish 27.2%; Middle Eastern 25.0%; Amish 39.8%.
Estimated AA genotype frequency.
Showing effects for A/A genotype
Neurology & Mental Health
Psychotic Disorders
Schizophrenia. Evidence: 9/10. Source: PMID 25056061. Typical Risk.
Mood Disorders
Depression. Evidence: 8/10. Source: PMID 31835028. Typical Risk.
Bipolar Disorder. Evidence: 8/10. Source: PMID 31835028. Typical Risk.
Sleep & Circadian Rhythm
Insomnia. Evidence: 8/10. Source: PMID 30804565. Typical Risk.
Addiction & Reward
Opioid Use Disorder. Evidence: 8/10. Source: PMID 36171425. Typical Risk.
Behavioral & Personality Traits
Risk-Taking Behavior. Evidence: 8/10. Source: PMID 30643258. Typical.
Showing effects for G/A genotype
Schizophrenia. Evidence: 9/10. Source: PMID 25056061. Slightly Increased.
Depression. Evidence: 8/10. Source: PMID 31835028. Slightly Increased.
Bipolar Disorder. Evidence: 8/10. Source: PMID 31835028. Slightly Increased.
Insomnia. Evidence: 8/10. Source: PMID 30804565. Slightly Increased.
Opioid Use Disorder. Evidence: 8/10. Source: PMID 36171425. Slightly Increased.
Risk-Taking Behavior. Evidence: 8/10. Source: PMID 30643258. Slightly Increased.
Showing effects for G/G genotype
Schizophrenia. Evidence: 9/10. Source: PMID 25056061. ~1.08x Risk.
Depression. Evidence: 8/10. Source: PMID 31835028. Increased Risk.
Bipolar Disorder. Evidence: 8/10. Source: PMID 31835028. ~1.06x Risk.
Insomnia. Evidence: 8/10. Source: PMID 30804565. Increased Risk.
Opioid Use Disorder. Evidence: 8/10. Source: PMID 36171425. ~1.07x Risk.
Risk-Taking Behavior. Evidence: 8/10. Source: PMID 30643258. Increased Tendency.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Having two copies of the protective A allele means the regulatory region of the gene functions at a standard baseline. This prevents a specific microRNA from binding and suppressing the expression of the FURIN enzyme [1]. Consequently, brain cells can efficiently process precursor molecules into mature brain-derived neurotrophic factor (BDNF), which supports healthy neural connections and synaptic plasticity [1]. Large-scale genomic studies show that individuals with this genotype have a typical baseline risk for several psychiatric conditions, including schizophrenia and major depressive disorder [2]. They also tend to show typical patterns of sleep quality and risk-taking behavior [3]. This genetic profile represents the most common baseline in many global populations, providing standard neurotrophic support to the brain.
Typical BDNF maturation; Baseline risk of psychiatric conditions; Typical sleep patterns.
Sample genotype: GA (Heterozygous)
Having one copy of the G allele introduces a binding site for a microRNA that suppresses the expression of the FURIN gene, leading to a partial reduction in mature brain-derived neurotrophic factor (BDNF) [1]. BDNF is vital for maintaining synaptic plasticity and healthy neural connections across brain regions [2]. This reduction in neurotrophic support is associated with a slightly higher susceptibility to psychiatric conditions, including schizophrenia, major depression, and bipolar disorder [3]. Research indicates that carriers may also experience a minor increase in risk-taking behaviors and sleep disturbances like insomnia [4]. While the genetic influence is real, it represents only a small piece of the overall risk puzzle, which is heavily shaped by environmental factors.
Slightly reduced BDNF maturation; Slightly higher risk of mood conditions; Increased susceptibility to insomnia.
Sample genotype: GG (Homozygous)
Individuals with the G/G genotype have two copies of the risk allele, which maximizes the microRNA-mediated suppression of FURIN expression in the brain [1]. This suppression significantly impairs the processing of precursor BDNF into its active, mature form, which is essential for healthy brain development and synaptic plasticity [1]. Consequently, this genotype is consistently linked to the highest genetic risk at this locus for schizophrenia, major depressive disorder, and bipolar disorder [2]. It is also associated with an increased likelihood of sleep issues such as insomnia and a higher tendency toward risk-taking behaviors [3]. Despite this genetic predisposition, having this genotype does not guarantee the development of any condition, as lifestyle, coping strategies, and environmental factors play massive roles.
Reduced BDNF maturation; Elevated risk of psychiatric conditions; Higher likelihood of insomnia.
Variants with shared genetic architecture
rs17514846 · FURIN Gene · Chr 15 · Heart Disease Risk
rs1006737 · CACNA1C Gene · Chr 12 · Mental Health Risk
rs1042779 · ITIH1 Gene · Chr 3 · Bipolar Disorder Risk
Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders.
Multi-trait analysis for genome-wide association study of five psychiatric disorders.
Content updated August 2026.
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