Mood & Behavior

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

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 variant near the MEF2C transcription factor locus associated with increased risk of major depressive disorder through altered neuronal synapse regulation

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

Intronic variant in the neurotrophin sorting receptor SORCS3, the top GWAS hit for major depression in the Howard et al. 2019 meta-analysis of 807,553 individuals; the G allele impairs glutamate receptor trafficking, fear extinction, and synaptic plasticity

Intronic variant in the BDNF-receptor trafficking gene SORCS3, associated with mood instability, neuroticism, reduced wellbeing, and cross-disorder psychiatric risk across multiple large GWAS

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

Intronic variant in SLC12A5 reducing KCC2 potassium-chloride cotransporter function, shifting GABA signaling from inhibitory to excitatory and increasing risk for depression and anxiety

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

3' UTR variant in the TrkB receptor gene affecting NTRK2 expression; associated with treatment-resistant depression susceptibility and lithium/mood-stabilizer response through BDNF signaling pathway effects

Intronic variant reducing SLC6A15 expression in hippocampus; AA carriers show increased susceptibility to major depression and hyperactive HPA stress responses

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

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

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

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

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

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

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

Intronic variant near the CNR1 exon 3 alternative promoter that modulates CB1 receptor mRNA isoform balance; the C (risk) allele is associated with greater hippocampal volume loss in heavy cannabis users, heightened cannabis withdrawal and craving, and participation in a female-specific nicotine dependence haplotype

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

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

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

Intronic variant in the presynaptic scaffold gene PCLO linked to altered monoaminergic neurotransmission, increased depression and anxiety risk, and heightened amygdala reactivity to emotional stimuli

Missense variant in the C2A calcium-binding domain of presynaptic scaffolding protein Piccolo, altering monoamine vesicle release efficiency and modulating HPA axis reactivity — associated with elevated depression risk and altered antidepressant treatment response

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

Intergenic tag SNP near NEGR1 associated with elevated BMI and major depression risk through hypothalamic NEGR1 expression — one of the most replicated obesity GWAS loci and a genome-wide significant depression locus

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

Intronic tag SNP in NEGR1 affecting neuronal cell adhesion, hippocampal neurogenesis, and monoaminergic neurotransmission — the G allele is associated with increased risk of major depression, anxiety disorders, and elevated BMI through shared hypothalamic circuits

Intronic/3'UTR variant in LHPP, a histidine phosphatase essential for stress resilience in the prefrontal cortex — the T allele is associated with increased risk for major depressive disorder, particularly following chronic stress

Intronic glucocorticoid receptor variant affecting cortisol sensitivity and stress response regulation

Intronic variant in the brain neurosteroid hydroxylase gene affecting DHEA and pregnenolone catabolism, linked to GABAergic tone and anxiety risk in GWAS

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

A 3'UTR regulatory variant where the G allele creates a miR-338-3p binding site that suppresses FURIN expression, reducing cleavage of proBDNF to mature BDNF and shifting neurotrophin signaling toward pro-apoptotic pathways

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

CHRNA3 3' UTR variant at 15q25.1 Locus 2 — mechanistically distinct from rs1051730, associated with blunted reward sensitivity to natural stimuli and heightened neural response to cigarette cues

Intronic eQTL in CHRNA5 that modulates alpha-5 nicotinic receptor mRNA expression levels, forming an independent risk signal for nicotine dependence and lung cancer distinct from the Asp398Asn coding variant (rs16969968)

Functional promoter variant in the serotonin 1A receptor gene that increases autoreceptor expression in raphe neurons and reduces serotonergic output, predicting poor antidepressant response

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

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

Intronic variant in the cannabinoid receptor 1 gene that modulates substance dependence vulnerability through a gene-gene interaction with rs806368; the G allele increases risk for drug and alcohol dependence and sits in a completely independent LD block from the rs806368/rs1049353 haplotype

Intronic variant in the neuronal membrane glycoprotein M6a gene — a stress-downregulated scaffold protein critical for dendritic spine formation and synaptic plasticity; G allele associated with anxiety disorders in a major multi-ancestry GWAS

Intronic variant in the gene encoding the inhibitory synaptic adhesion protein IgSF9b, which organizes GABAergic synapses in the centromedial amygdala and modulates anxiety-relevant inhibitory signaling

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

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

Regulatory variant near STK24 (MST3), a kinase essential for hippocampal neurogenesis and neuronal migration — the G allele is associated with disrupted HPA axis stress reactivity and anxiety-like phenotypes

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