Brain & Mental Health

Key neurotrophin variant that controls activity-dependent BDNF release, affecting memory consolidation, neuroplasticity, and stress resilience

Reduces dopamine D2 receptor density in the striatum, affecting reward processing, reinforcement learning, and addiction susceptibility

Promoter variant that modulates dopamine D4 receptor expression in the prefrontal cortex, influencing novelty seeking and cognitive flexibility

Strongest known genetic determinant of dopamine beta-hydroxylase activity, controlling the dopamine-to-norepinephrine ratio

Influences episodic memory performance and hippocampal function through the KIBRA protein's role in synaptic plasticity

Co-chaperone of the glucocorticoid receptor that regulates cortisol feedback — the T allele impairs stress recovery and, combined with early adversity, strongly increases risk of PTSD and depression

Most-studied oxytocin receptor variant, influencing empathy, social sensitivity, stress resilience through social buffering, and emotional regulation

Promoter variant affecting brain serotonin synthesis enzyme; influences emotional reactivity, anxiety, and depression risk

Regulatory variant in serotonin 2A receptor gene affecting SSRI side effects and potentially treatment response

GABA-A receptor alpha-2 subunit variant affecting alcohol response, anxiety, and addiction vulnerability

Affects anandamide levels through altered FAAH enzyme stability, influencing pain sensitivity, stress response, fear extinction, and mood regulation

X-linked monoamine oxidase A variant affecting enzyme activity and neurotransmitter breakdown

Promoter SNP near 5-HTTLPR that modifies serotonin transporter expression and antidepressant response

Intronic glucocorticoid receptor variant affecting cortisol sensitivity and stress response regulation

Nicotinic receptor variant strongly associated with heavy smoking, nicotine dependence, and increased lung cancer risk

Second strongest genetic risk factor for Alzheimer's disease after APOE, associated with increased tau pathology and accelerated cognitive decline

Intronic variant in clusterin gene affecting Alzheimer's disease risk through regulation of amyloid-beta clearance

Rare missense variant in microglial receptor TREM2 that significantly increases late-onset Alzheimer's disease risk through impaired microglial function and amyloid clearance

Variant in the PICALM gene affecting amyloid-beta clearance across the blood-brain barrier and Alzheimer's disease risk

Parkinson's disease GWAS risk variant affecting alpha-synuclein expression and neuronal differentiation

Haplotype-tagging variant distinguishing MAPT H1 and H2 clades, affecting risk for Parkinson disease, progressive supranuclear palsy, and other tauopathies

Common variant in the Nav1.7 sodium channel affecting pain sensitivity and pain threshold

Capsaicin receptor variant affecting heat and pain sensitivity

Promoter variant affecting GTP cyclohydrolase 1 expression and pain sensitivity, with opposite effects in European vs African populations

Intronic variant affecting thermal pain sensitivity and central pain signal transmission

Loss-of-function variant in the P2X7 receptor that reduces inflammatory response and may modulate pain sensitivity

Common noncoding variant upstream of LRRK2 that increases gene expression in microglia and Parkinson's disease risk

L-type calcium channel gene variant affecting mood regulation, emotional processing, and psychiatric disorder risk

Upstream regulatory variant of the cold-sensing TRPM8 channel that modulates migraine susceptibility, cold pain sensitivity, and brown adipose thermogenesis

Missense variant in the orexin/hypocretin receptor 1 that alters G-protein signaling, increasing susceptibility to migraine, panic disorder, mood dysregulation, and heightened arousal responses

Promoter variant in neuropeptide Y that modulates NPY expression under stress, affecting stress resilience, anxiety vulnerability, appetite regulation, and migraine susceptibility

Promoter/5' UTR variant in the serotonin 5-HT5A receptor gene affecting receptor expression, linked to schizophrenia susceptibility and executive function

The most common cause of autosomal recessive nonsyndromic hearing loss in Europeans; homozygous deletion eliminates connexin 26 function and causes severe-to-profound congenital deafness

Connexin 26 missense variant causing partial loss of cochlear gap junction function; the leading cause of mild-to-moderate hereditary hearing loss in East Asian populations

Near-gene variant tagging the TMPRSS3 hearing loss locus on chromosome 21, associated with susceptibility to sensorineural hearing loss and carrier status for DFNB8/10 deafness

ADH1B variant encoding a ~100x faster alcohol dehydrogenase enzyme, causing rapid acetaldehyde accumulation, the "Asian flush" response, and strong protection against alcoholism — but elevated esophageal cancer risk in carriers who drink

3'UTR variant in the cannabinoid receptor 1 gene that regulates CB1 expression in the brain and modulates vulnerability to cannabis, alcohol, nicotine, and cocaine dependence, as well as impulsivity and emotional reactivity

SNCA 3′-region regulatory variant that upregulates alpha-synuclein expression and independently increases Parkinson's disease risk, earlier onset, and cognitive decline

Synonymous exon 4 variant in the cannabinoid receptor 1 gene; near an exon splice enhancer, it alters CB1 mRNA stability and modulates vulnerability to cannabis-induced brain changes, PTSD after trauma, and antidepressant treatment response

Intronic MAPT variant that regulates tau exon 3 splicing via hnRNP F/Q binding, distinguishing H1 (risk) from H2 (protective) haplotypes for Parkinson's disease, PSP, corticobasal degeneration, and Alzheimer's disease

Intronic MAPT variant tagging the H1c sub-haplotype within the H1 clade, independently elevating risk for progressive supranuclear palsy and corticobasal degeneration through increased 4-repeat tau expression

Intronic variant in the anti-apoptotic gene BCL2 that affects BCL2 expression levels, intracellular calcium homeostasis, and rate of age-related gray matter loss in key brain regions

Gain-of-function missense variant in the P2X7 ATP-gated receptor that increases receptor expression and ion channel activity, heightening neuroinflammation and linked to mood disorders, pain sensitization, and infection severity

Gain-of-function variant in the P2X7 receptor that increases ATP-gated pore formation, IL-1β release, and microglial neuroinflammation, associated with mood disorders and chronic pain severity

P2RX7 variant with a unique dual mechanism — gain-of-function in channel opening and loss-of-function in pore formation — associated with chronic pain susceptibility, neuroinflammation, and modulation of microglial signaling

CHRNA3 synonymous variant in the nicotinic receptor gene cluster strongly associated with heavy smoking, nicotine dependence, lung cancer, and COPD, with independent effects in non-European populations

Stop-gain mutation eliminating connexin 26 function; the most common GJB2 deafness allele in South Asian populations and the ancestral founder mutation carried into European Romani communities

The most common GJB2 deafness allele in the Ashkenazi Jewish population (~4% carrier frequency); frameshift deletion eliminates connexin 26 function and causes congenital sensorineural hearing loss in homozygotes or compound heterozygotes

Frameshift deletion eliminating connexin 26 function; the most common GJB2 deafness allele in East Asian populations causing severe-to-profound prelingual sensorineural hearing loss

Connexin 26 missense variant causing partial loss of cochlear gap junction function; the main mild-severity GJB2 deafness allele in European populations, with reduced penetrance and typically mild-to-moderate hearing loss

Frameshift deletion in TMPRSS3 causing premature stop at codon 88; a severe pathogenic allele and Slovenian founder mutation causing DFNB8/10 autosomal recessive sensorineural hearing loss

Pathogenic missense variant at the TMPRSS3 autocatalytic cleavage site causing serine protease domain dysfunction and autosomal recessive sensorineural hearing loss (DFNB8/DFNB10); originally identified in consanguineous Turkish families

ADH1B*3 variant encoding a superactive alcohol dehydrogenase found almost exclusively in people of African descent, providing strong independent protection against alcoholism by accelerating the conversion of ethanol to acetaldehyde

ADH1C variant defining the fast (ADH1C*1, Arg272) vs slow (ADH1C*2, Gln272) alcohol dehydrogenase isoforms; ADH1C*1 metabolizes ethanol ~2.5x faster, elevating cancer risk in heavy drinkers, while ADH1C*2 slows metabolism and reduces alcohol use disorder risk

Intronic SNCA variant (intron 4) associated with Parkinson's disease risk and cognitive impairment; the G allele upregulates alpha-synuclein protein levels and is independent of rs356219

SNCA 3′-region variant in the extended 3′ UTR that affects alpha-synuclein mRNA stability and expression, consistently associated with Parkinson's disease risk across Asian and European populations

Missense variant in the C-terminal domain of the P2X7 receptor that disrupts normal receptor dimerisation when coexpressed with the wild-type allele, with the G (Arg460) allele associated with major depressive disorder in a large meta-analysis and with higher multiple sclerosis severity scores; the A (Gln460, low-activity) allele is independently linked to rapid cycling in bipolar disorder

Cis-regulatory enhancer variant at 15q25.1 that drives CHRNA3 and CHRNA5 expression via chromatin looping, independently associated with nicotine dependence and lung cancer risk — particularly informative in non-European populations

Intronic variant near CHRNA3 at 15q25.1 that acts as an eQTL for nicotinic receptor genes and is independently associated with heavy smoking and lung cancer risk

Hypomorphic missense variant in the TMPRSS3 serine protease catalytic domain; the most common TMPRSS3 pathogenic allele worldwide, causing DFNB8 progressive or DFNB10 congenital hearing loss depending on the second allele; a founder mutation in Korean, Chinese, Dutch, and German populations

Intronic MAPT variant whose T allele co-defines the H1c sub-haplotype, independently conferring OR 1.85 for progressive supranuclear palsy and OR 2.07 for corticobasal degeneration in the same meta-analysis validating rs242557

Intronic MAPT variant that directly regulates tau exon 3 splicing via differential hnRNP F/Q binding; the G allele (H1 haplotype) reduces exon 3 inclusion, elevating 4-repeat tau isoforms and increasing risk for Parkinson's disease, PSP, and corticobasal degeneration