HealthRec | Addiction SNP-Behavior Intelligence

A1 allele reduces striatal D2 receptor density ~30-40%, creating reward deficiency that drives addiction vulnerability across substances and behaviors.

ANKK1 Taq1A shares rs1800497 with DRD2 and contributes to reward deficiency through both receptor density and kinase signaling mechanisms.

DRD4 7-repeat allele reduces D4 receptor sensitivity ~3-fold, driving novelty-seeking, impulsivity, and elevated substance use/ADHD risk.

DAT1 10-repeat allele increases dopamine transporter expression, accelerating dopamine clearance and driving stimulant vulnerability and ADHD.

COMT Val158Met creates either prefrontal dopamine deficiency (Val/Val) or stress/pain hypersensitivity (Met/Met), producing distinct but convergent addiction vulnerability pathways.

DDC rs3837091 impairs DOPA decarboxylase activity, reducing both dopamine and serotonin synthesis efficiency and increasing addiction vulnerability.

TH rs10770141 limits dopamine synthesis at the rate-limiting step, creating constitutive hypodopaminergic vulnerability dependent on cofactor status.

5-HTTLPR S allele reduces serotonin transporter expression, creating stress-reactive serotonin dysregulation and anxiety-driven addiction vulnerability with reduced SSRI efficacy.

HTR2A T102C C allele increases 5-HT2A receptor density, altering serotonergic modulation of reward circuits and psychedelic/alcohol sensitivity.

HTR1B G861C C allele impairs serotonin autoreceptor feedback, increasing impulsive aggression, alcohol preference, and antisocial addiction phenotypes.

MAOA VNTR creates either impulsive/aggressive vulnerability (low-activity) or depressive self-medication risk (high-activity), with trauma exposure dramatically amplifying low-activity effects.

MAOB rs1799836 modulates dopamine catabolism and influences tobacco dependence treatment response to MAOB inhibitors like selegiline.

TPH2 rs4570625 T allele reduces brain serotonin synthesis capacity, creating depressive/anxious vulnerability that drives alcohol and opioid self-medication.

OPRM1 A118G G allele increases mu-opioid receptor sensitivity and confers ~3x better naltrexone response — the best-validated pharmacogenomic interaction in addiction medicine.

OPRD1 T921C modulates delta-opioid receptor function, influencing negative-affect tolerance during withdrawal and relapse vulnerability.

OPRK1 rs6473797 modulates kappa-opioid receptor function, influencing stress-induced craving and relapse vulnerability in opioid and cocaine use disorders.

GABRA2 rs279858 C allele reduces GABA-A inhibitory tone, enhancing alcohol reward, increasing benzodiazepine sensitivity, and driving impulsive/externalizing addiction phenotypes.

GABRB3 rs4906902 alters GABA-A beta-3 subunit function, increasing benzodiazepine sensitivity and contributing to alcohol/benzodiazepine dependence risk.

GRIN2B rs2058878 modulates NMDA glutamate receptor function, affecting addiction memory formation, withdrawal seizure risk, and acamprosate efficacy.

GRIN2A rs1969060 affects NMDA receptor subunit composition, contributing to cognitive vulnerability in addiction through impaired executive function.

CYP2D6 *4 Poor Metabolizer eliminates metabolism of codeine, tramadol, and many antidepressants — critical pharmacogenomic safety and efficacy determinant in addiction medicine.

CYP3A4 *1B variant alters metabolism of all frontline OUD medications — methadone, buprenorphine, and fentanyl.

CYP2A6 *2 slows nicotine clearance — slow metabolizers smoke less, quit more easily, and respond better to NRT than varenicline.

ALDH2 rs671 (*2) causes acetaldehyde buildup after drinking — protective against AUD but disulfiram is dangerous and cancer risk is high if drinking continues.

ADH1B His48 variant speeds acetaldehyde production after drinking, providing mild natural protection against AUD — most Europeans lack this protective allele.

ADH1C Ile350 fast-metabolizer variant increases acetaldehyde production with alcohol, linking AUD to elevated cancer risk.

CRHR1 rs110402 T allele amplifies stress-induced relapse circuitry — especially dangerous in trauma survivors with substance use disorders.

FKBP5 rs1360780 T allele creates trauma-activated epigenetic HPA dysregulation — the strongest known gene-environment interaction in addiction-PTSD comorbidity.

BDNF Val66Met reduces activity-dependent neuroplasticity — Met carriers have sticky drug cue memories and higher relapse risk.

NR3C1 BclI variant alters glucocorticoid receptor sensitivity, modifying stress reactivity and addiction vulnerability.

NR3C2 (mineralocorticoid receptor) rs5522 modifies stress appraisal and resilience, contributing to compound HPA-addiction vulnerability.

CNR1 rs1049353 alters CB1 receptor expression — G allele carriers have elevated cannabis dependence risk and modified endocannabinoid tone.

FAAH C385A A allele reduces enzyme activity, naturally elevating anandamide — creating stress resilience but modifying cannabis pharmacodynamics.

MGLL rs604300 affects 2-AG degradation — part of the endocannabinoid system triad shaping cannabis dependence risk and opioid cross-tolerance.

ADRA2A rs1800544 G allele reduces alpha-2A receptor expression — creates ADHD-stimulant vulnerability overlap and makes guanfacine a targeted treatment option.

DBH rs1611115 T allele produces low DBH enzyme activity — dopamine excess and NE deficiency creates stimulant vulnerability and elevated cocaine craving.

SLC6A2 (NET) rs2242446 modifies norepinephrine reuptake efficiency — relevant to ADHD pharmacotherapy dosing and stimulant use disorder vulnerability.

CHRNA5 rs16969968 A allele is the strongest single genetic predictor of nicotine dependence severity — A/A homozygotes need maximum-intensity cessation intervention.

CHRNB2 rs2072661 G allele predicts severe nicotine withdrawal — pre-cessation pharmacotherapy is essential for G allele carriers.

CHRNA3 rs1051730 T allele tags the 15q25 nicotine dependence locus — works with CHRNA5 to create composite nAChR vulnerability score.

CHRNA4 rs2273504 modifies alpha-4/beta-2 nicotinic receptor properties — relevant to varenicline pharmacodynamics and cessation response.

MTHFR C677T reduces enzyme activity 35-70%, impairing methylation, neurotransmitter synthesis, and homocysteine clearance — one of the most actionable variants in addiction-depression overlap.

MTHFR A1298C reduces enzyme activity and BH4 production — compound heterozygosity with C677T creates significant methylation deficiency affecting all neurotransmitter pathways.