rs324420

This is a variant in the FAAH gene that changes a proline to an threonine.

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GWAS Catalog Trait Associations (13)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

N-palmitoylglycine measurement

Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)
Allele A
OR 0.50
p 2.0e-131
N 6,136
Large GWAS
European
Hysi PG et al. “Metabolome Genome-Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels.” Metabolites 12(1) (2022)
Allele A
OR 0.39
p 5.0e-96
N 8,809
Large GWAS
European
Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)
Allele A
OR 0.34
p 1.0e-76
N 8,236
Large GWAS
European
Feofanova EV et al. “Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations.” Nature Communications 14(1):3111 (2023)
Allele A
OR 0.44
p 9.0e-123
N 7,733
Large GWAS
multi-ancestry
Schlosser P et al. “Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine.” Nature Genetics 55(6):995-1008 (2023)
Allele A
OR 0.20
p 2.0e-41
N 4,918
Large GWAS
European

metabolite measurement

Tahir UA et al. “Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals.” Nature Communications 13(1):4923 (2022)
Allele A
OR 0.71
p 3.0e-123
N 2,466
Large GWAS
multi-ancestry
Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)
Allele A
OR 0.14
p 5.0e-13
N 8,106
Large GWAS
European
Schlosser P et al. “Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine.” Nature Genetics 55(6):995-1008 (2023)
Allele A
OR 0.25
p 7.0e-21
N 4,912
Large GWAS
European

oleoyl ethanolamide measurement

Feofanova EV et al. “Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations.” Nature Communications 14(1):3111 (2023)
Allele A
OR 0.40
p 5.0e-104
N 7,867
Large GWAS
multi-ancestry
Hysi PG et al. “Metabolome Genome-Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels.” Metabolites 12(1) (2022)
Allele A
OR 0.36
p 1.0e-83
N 8,809
Large GWAS
European
Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)
Allele A
OR 0.27
p 2.0e-47
N 8,243
Large GWAS
European
Schlosser P et al. “Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine.” Nature Genetics 55(6):995-1008 (2023)
Allele A
OR 0.24
p 6.0e-30
N 4,772
Large GWAS
European

N-linoleoyltaurine measurement

Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)
Allele A
OR 0.50
p 1.0e-74
N 6,136
Large GWAS
European

oleoyl glycine measurement

Tahir UA et al. “Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals.” Nature Communications 13(1):4923 (2022)
Allele A
OR 0.55
p 6.0e-64
N 2,466
Large GWAS
multi-ancestry
Rhee EP et al. “Trans-ethnic genome-wide association study of blood metabolites in the Chronic Renal Insufficiency Cohort (CRIC) study.” Kidney International 101(4):814-823 (2022)
Allele A
OR 0.39
p 2.0e-14
N 822
Small GWAS
European

linoleoyl ethanolamide measurement

Hysi PG et al. “Metabolome Genome-Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels.” Metabolites 12(1) (2022)
Allele A
OR 0.32
p 8.0e-59
N 8,809
Large GWAS
European
Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)
Allele A
OR 0.22
p 2.0e-30
N 7,214
Large GWAS
European

N-oleoyltaurine measurement

Feofanova EV et al. “Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations.” Nature Communications 14(1):3111 (2023)
Allele A
OR 0.26
p 3.0e-40
N 7,112
Large GWAS
multi-ancestry
Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)
Allele A
OR 0.24
p 2.0e-35
N 7,375
Large GWAS
European
Schlosser P et al. “Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine.” Nature Genetics 55(6):995-1008 (2023)
Allele A
OR 0.21
p 7.0e-24
N 3,985
Large GWAS
European

N-oleoylserine measurement

Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)
Allele A
OR 0.23
p 2.0e-32
N 7,591
Large GWAS
European
Feofanova EV et al. “Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations.” Nature Communications 14(1):3111 (2023)
Allele A
OR 0.21
p 1.0e-22
N 5,807
Large GWAS
multi-ancestry
Schlosser P et al. “Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine.” Nature Genetics 55(6):995-1008 (2023)
Allele A
OR 0.13
p 2.0e-16
N 4,617
Large GWAS
European

oleoyl serine measurement

Tahir UA et al. “Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals.” Nature Communications 13(1):4923 (2022)
Allele A
OR 0.38
p 4.0e-32
N 2,466
Large GWAS
multi-ancestry

X-16570 measurement

Surendran P et al. “Rare and common genetic determinants of metabolic individuality and their effects on human health.” Nature Medicine 28(11):2321-2332 (2022)
Allele A
OR 0.13
p 7.0e-24
N 14,296
Large GWAS
European
Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)
Allele A
OR 0.16
p 9.0e-15
N 6,136
Large GWAS
European
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ClinVar annotation

Likely Benign★☆☆☆
4 submitters6 publications

FAAH POLYMORPHISM; FAAH-related disorder; PAIN SENSITIVITY QUANTITATIVE TRAIT LOCUS 1 (PAINQTL1); Polysubstance abuse, susceptibility to (PSAB)

View on ClinVar →
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Research that mentions this SNP (6)

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Genetic variation in the endocannabinoid system and response to Cognitive Behavior Therapy for child anxiety disorders
AssociationN=1,309Kathryn J. Lester et al.(2017)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

This study investigated genetic variation in the endocannabinoid system (CNR1, CNR2, FAAH genes) as a predictor of response to cognitive behavior therapy for childhood anxiety disorders in 1,309 children aged 5-17 years. Six SNPs showed nominal associations (P<0.05) with treatment response during follow-up: rs806365 (CNR1, P=0.004), rs2501431 (CNR2), rs2070956 (CNR2), rs7769940 (CNR1), rs2209172 (FAAH) associated with poorer response, and rs6928813 (CNR1) with better response. Only rs806365 survived multiple testing corrections in the fear-based anxiety disorder subset (P=0.0011). The authors conclude there is very limited evidence for genetic variation in endocannabinoid system genes predicting CBT treatment response.

Traits studied:Anxiety disordersCBT treatment responseGeneralized anxiety disorderObsessive-compulsive disorderPanic disorderPost-traumatic stress disorderSeparation anxiety disorderSocial anxiety disorderSpecific phobia
PubMedDOIMetascience Observatory
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Risky alcohol consumption in young people is associated with the fatty acid amide hydrolase gene polymorphism C385A and affective rating of drug pictures
AssociationN=260Kora-Mareen Bühler et al.(2014)· Molecular Genetics and Genomics

This candidate gene association study examined 10 SNPs in addiction-related genes (CNR1, FAAH, DRD2, ANKK1, COMT, OPRM1) in university students and identified the FAAH C385A (rs324420) CC genotype as significantly associated with risky alcohol consumption (p=0.006, OR=2.38). The finding was replicated in an independent sample of 83 participants. Additionally, affective ratings of drug-related pictures were positively correlated with alcohol, tobacco, and cannabis consumption.

Traits studied:Affective rating of drug-related picturesAlcohol consumption (risky drinking)Cannabis consumptionTobacco consumption
PubMedDOIMetascience Observatory
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Promoter variants of the cannabinoid receptor 1 gene (CNR1) in interaction with 5‐HTTLPR affect the anxious phenotype
AssociationN=154Judit Lazary et al.(2009)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

This longitudinal study of 154 traumatized injury survivors examined associations between circulating endocannabinoids and CNR1/FAAH/MGLL genetic variants with depression severity at 6 months post-injury. Higher post-injury serum 2-arachidonylglycerol (2-AG) concentrations predicted greater depression severity at 6 months (β = 0.23, p = 0.007), and carriers of the minor allele (G) at CNR1 rs806371 experienced significantly greater depression (β = 0.19, p = 0.024), supporting a role for endocannabinoid system dysfunction in post-trauma depression risk.

Traits studied:DepressionMajor depressive disorder
PubMedDOIMetascience Observatory
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Intermediate cannabis dependence phenotypes and the FAAH C385A variant: an exploratory analysis
AssociationN=38Joseph P. Schacht et al.(2009)· Psychopharmacology

This candidate gene association study examined the FAAH C385A variant (rs324420) in 40 daily marijuana users to identify genetic influences on cannabis dependence phenotypes. The C allele was associated with greater withdrawal symptoms after 24-hour abstinence and increased happiness after smoking marijuana, while the A allele carriers showed higher heart rate reactivity 15 minutes post-smoking. Craving phenotypes showed no significant genotype associations.

Traits studied:Cannabis dependenceMarijuana cravingMarijuana withdrawalSensitivity to acute marijuana effects
PubMedDOIMetascience Observatory
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The functional Pro129Thr variant of the FAAH gene is not associated with various fat accumulation phenotypes in a population-based cohort of 5,801 whites
AssociationN=5,801Dorit P. Jensen et al.(2007)· Journal of Molecular Medicine

This case-control and quantitative trait study of 5,801 Danish whites examined the functional Pro129Thr variant (rs324420) of the FAAH gene in relation to obesity and metabolic traits. Despite previous reports of association between the homozygous Thr/Thr genotype and obesity, this large population-based study found no robust association after correcting for multiple testing, and no association with any obesity-related quantitative traits including BMI, waist circumference, or insulin resistance.

Traits studied:Body mass index (BMI)Fasting plasma glucoseHOMA-IRObesityOverweightSerum C-peptideSerum cholesterolSerum insulinSerum triglyceridesWaist circumferenceWaist-to-hip ratio
PubMedDOIMetascience Observatory
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The fatty acid amide hydrolase 385 A/A (P129T) variant: haplotype analysis of an ancient missense mutation and validation of risk for drug addiction
AssociationN=1,034Jonathan M. Flanagan et al.(2006)· Human Genetics

This case-control association study examined the FAAH P129T (c.385 C>A) missense mutation in 249 drug-addicted subjects and 785 controls across three ethnic groups. The P129T homozygote genotype showed significant association with multiple drug addiction (P=0.05, OR=2.25 in the case-control study; P=0.00003, OR=3.20 when combined with prior data). Haplotype analysis identified a single ancestral origin and estimated the P129T mutation age at 114,425-177,525 years.

Traits studied:alcohol addictioncocaine addictiondrug addictionecstasy addictionheroin addictionmethamphetamine addictionpolysubstance dependence
PubMedDOIMetascience Observatory

About FAAH

This gene encodes a protein that is responsible for the hydrolysis of a number of primary and secondary fatty acid amides, including the neuromodulatory compounds anandamide and oleamide. [provided by RefSeq, Jul 2008]

View all FAAH variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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