rs324420

Chromosome : 1 , Position: 46405089

Most conditions are affected by anywhere from hundreds to millions of genetic variants (SNPs). A single SNP usually has a minor contribution to a person’s overall genetic risk for a certain condition. That is why you shouldn't consider or act on a SNP in isolation. Instead, we use SNPs to determine polygenic risk scores (PRSs), which are the basis of most health reports.

Reference Allele: C

Alternative Alleles: A

Associated Genes

FAAH

NSUN4

MKNK1

MOB3C

LURAP1

POMGNT1

PIK3R3

DMBX1

LRRC41

UQCRH

KNCN

RAD54L

TMEM275

EFCAB14

ATPAF1

P3R3URF

P3R3URF-PIK3R3

TEX38

TSPAN1

CYP4B1

Traits

Trait	Variant	PMID	Author (year)
Serum metabolite levels [N-palmitoylglycine]	A	Am J Hum Genet	Feofanova EV (2020)
Serum metabolite levels [oleoyl ethanolamide]	A	Am J Hum Genet	Feofanova EV (2020)
Serum metabolite levels [linoleoyl ethanolamide]	A	Am J Hum Genet	Feofanova EV (2020)
Serum metabolite levels [N-oleoyltaurine]	A	Am J Hum Genet	Feofanova EV (2020)
Serum metabolite levels [N-oleoylserine]	A	Am J Hum Genet	Feofanova EV (2020)
N-acyl ethanolamine levels [DHEA]	A	Hum Mol Genet	McGurk KA (2021)
N-acyl ethanolamine levels [LEA]	A	Hum Mol Genet	McGurk KA (2021)
N-acyl ethanolamine levels [PEA]	A	Hum Mol Genet	McGurk KA (2021)
N-acyl ethanolamine levels [VEA]	A	Hum Mol Genet	McGurk KA (2021)
N-acyl ethanolamine levels [sumEA]	A	Hum Mol Genet	McGurk KA (2021)

Summary

A=less likely to be dependent on cannabis [R]. A allele less likely to be cannabis dependent / C allele more likely to be dependent on cannabis & suffer more withdrawals [R]. A=lower FAAH. AA=high anandamide, 5X higher risk for substance abuse, does better with lower fat, more Slow wave sleep, lower risk of PTSD (fear extinction in amygdala) and less awake after 10mg amphetamines (but not 20mg).

Function

C encodes the more common Proline, while the A allele encodes the Threonine (R). The change displays normal enzymeproperties but an enhanced sensitivity to degradation (R). Functional in-vitro studies further revealed that the A alleledecreased the productionand activity of FAAH in humans(R). AA=half FAAH enzymatic activity (R), reduced FAAH production, increased degradation of the enzyme, and less cellular stability (R). These factors negatively impact FAAH, which increasesanandamide. (FAAH breaks anandamide down).

The Good

People with the A alleleare less anxious and are thus less inclined to like marijuana. They actually experience a decrease in happiness when smoking marijuana, compared with those with the normal FAAH gene, who find it pleasurable. If you naturally have more of the real thing you understandably have little use for marijuana (R).

Studies show that those with CCsuffer more severe withdrawal when they stop using cannabis (R).

For example, one community-based study of almost 2,100 healthy volunteers found that people with AAhad roughly half the rate (11 percent) of cannabis dependence than those one or more Cs(26 percent) (R).

Both mice and humans withthe A alleleshowed enhanced fear extinction(they learned more efficiently how to be unafraid) (R).

AA is calmer/less anxious, has lower enzyme activity, higher anandamide, enjoys pot less, less likely to get addicted to pot, does better with extinction therapy in PTSD (R). A has decreased threat-related amygdala reactivity and increased reward-related reactivity in the ventral striatumindicating its role in stress adaptation (R). Whenmice were genetically engineered to have the AA version of the gene, they were less anxious. The mice showed similar changes in the neural circuits involved in people with lower anxiety and fear(greater connectivity between the prefrontal cortex and the amygdala). A is less likely to develop cannabis dependence. In some studies (but not all), A is associated withobesity(R).

The Bad

AA is at higher risk for substance abuse. AC is normal risk (R). A has a synergistic effect on these conditions with the CB1 receptor gene (R).

In a study of 80 people and 1000 controls, AAwere 5X more likely to abuse drugs (p = 0.00003)(R,R2).

AA and AC have higher rate of anorexia (R).

One studyfound the exact opposite effect if some studies above and showed increased startle reaction in A carriers to unpleasant images (R).

The A allele was associated with lower HDL levels(R):

CC=40.5,
AC=39.1,
AA=34.8

Each 1 mg/dl reduction in circulating HDL level is known to be associated with a 6% increase in the risk for cardiovascular disease (R).

Diet Interactions

In 451 obese Europeans undergoing a 6 week trial of low-fat diet, subjects withAAexperienced greater reductions in circulating triglycerides and total cholesterol levels) (). After weight loss, CChad an improvement on insulin and insulin resistancescoreswith an enriched monounsaturated fat hypocaloric diet (R). People with anA allele lost less weight on thisenriched monounsaturated fat hypocaloric diet. People with an A lost only 2.7 kgfat mass (CC lost3.4 kg) (R).

Drug Interactions

Apsychoactiveingredient in cannabis helped people with IBS-C more when they had CC (R). The A allele is associated with antipsychotic-induced weight gain (R).

More Information

Linked to the FAAH gene. It is shown to be associated with drug abuse, and an increased risk for substance use disorders.

The A allele is associated with:

Early onset and adult obesity [R].
Anorexia nervosa and bulimia nervosa [R].
Lower HDL (high-density lipoprotein) levels [R].
Greater blood lipid reduction on a low fat diet [R].
Antipsychotic-induced weight gain (greatest in heterozygous AC genotype) [R, R].

The C allele is associated with:

Favourable response to cannabinoids in people with IBS [R].
Better response to a high monounsaturated fat hypocaloric diet [R].
Increased reward response to cannabinoids [R].

Population Alleles Frequency

ethhicity	frequency
African/African-American	0.3658
Latino/Admixed American	0.3404
Ashkenazi Jewish	0.1759
East Asian	0.1742
European	0.2339
Other (population not assigned)	0.2583

Frequently Asked Questions

Why Are Alleles for This SNP Different Elsewhere? Major vs. Reference Allele Is My Variant Good or Bad? SNP vs. Mutation

Unlock Personalized Results And So Much More!

Shipping Worldwide

30-Days Money-Back Guarantee*

HSA/FSA Eligible

Essential Bundle

SelfDecode DNA Kit

24/7 AI Health Coach
1250+ Comprehensive DNA Health Reports
Personalized Diet, Supplement, & Lifestyle Recommendations
Lifestyle Risk Assessments
Unlimited access to Labs Analyzer

$418

$376

Men's Health Month 10% Off

Essential

Bundle

Everything in essential
SelfDecode DNA Kit
Methylation Pathway
+130 Medical Reports
25+ Longevity Screener Risk Assessments

Odds ratios to evaluate your risk for 25+ medical conditions
10-year risk scores to prioritize health conditions
Lifetime risk scores to plan for long-term health

$667

$566

Men's Health Month 15% Off

Men's Health Month 30% Off

Ultimate Bundle

Everything in essential+
SelfDecode DNA Kit
Medication Check (PGx testing) for 50+ medications
40+ Family Planning (Carrier Status) Reports
Ancestry Percentages
Mitochondrial Ancestry

$894

$625

* SelfDecode DNA kits are non-refundable. If you choose to cancel your plan within 30 days you will not be refunded the cost of the kit.

We will never share your data

We follow HIPAA and GDPR policies

We have World-Class Encryption & Security

People Love Us

Rated 4.7/5 from 750+ reviews

People Trust Us

200,000+ users, 2,000+ doctors & 80+ businesses

SelfDecode is a personalized health report service, which enables users to obtain detailed information and reports based on their genome. SelfDecode strongly encourages those who use our service to consult and work with an experienced healthcare provider as our services are not to replace the relationship with a licensed doctor or regular medical screenings.

Policies

About

Support
Our Team
Affiliate Program
Privacy
Media