rs838133

badMag 3.5

This is a intergenic variant variant in the FUT2 gene.

Key Literature Trait Associations

Sweet Food Preference

Each copy of the A allele at rs838133 is associated with increased preference for sweet-tasting foods and higher sugar intake. This variant lies in the FUT1/FUT2 locus encoding fucosyltransferases involved in gut mucosal glycosylation and microbiome composition, which may influence taste perception and dietary behavior. The association was identified in a GWAS meta-analysis of 91,114 European ancestry participants from the CHARGE consortium.

Frayling TM et al. “A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure.” Cell Reports (2018)

Allele A

OR —

p —

N 451,099

Preliminary work

European

Merino J et al. “Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the cohorts for heart and aging research in genomic epidemiology consortium.” Molecular Psychiatry 24(12):1920-1932 (2019)

Allele A

OR —

β 0.080

p 2.4e-8

Meta-analysisMajor Consortium Study

Chu AY et al. “Novel locus including FGF21 is associated with dietary macronutrient intake.” Human Molecular Genetics 22(9):1895-902 (2013)

Allele A

OR —

p 7.9e-9

N 71,893

Large GWAS

multi-ancestry

Janzi S et al. “Single Nucleotide Polymorphisms in Close Proximity to the Fibroblast Growth Factor 21 (FGF21) Gene Found to Be Associated with Sugar Intake in a Swedish Population.” Nutrients (2021)

Allele A

OR —

p 6.8e-7

N 22,794

Small GWAS

Swedish

Søberg S et al. “FGF21 Is a Sugar-Induced Hormone Associated with Sweet Intake and Preference in Humans.” Cell Metabolism (2017)

Allele A

OR —

p —

N 6,514

Preliminary work

Danish

Carbohydrate intake

The A allele at rs838133 consistently associates with a higher proportion of calories derived from carbohydrates across large GWAS and meta-analyses. The CHARGE/DietGen meta-analysis (n>71,000) reached genome-wide significance (p=7.9×10⁻⁹) for this phenotype, and the association was replicated in 451,099 UK Biobank participants. Mendelian randomization analyses using this locus confirm that FGF21 signaling causally influences macronutrient selection, with higher FGF21 activity linked to reduced carbohydrate preference and the A allele blunting that suppression. The effect appears to operate through FGF21's role as a sucrose-responsive hepatokine that modulates hypothalamic sweet-taste reward circuits.

Chu AY et al. “Novel locus including FGF21 is associated with dietary macronutrient intake.” Human Molecular Genetics 22(9):1895-902 (2013)

Allele A

OR —

p 7.9e-9

N 71,893

Large GWAS

multi-ancestry

Ramne S et al. “Distinct genetic signals at the FGF21 locus complicate studies of FGF21's role in diet regulation using human cohort data.” Molecular Metabolism (2024)

Allele A

OR —

p —

N 157,508

Preliminary work

European

Alcohol intake

The A allele at rs838133 has been associated with higher alcohol intake in multiple studies, although the signal is generally nominally significant rather than genome-wide in most individual cohorts. Søberg et al. (2017) observed nominal associations with increased alcohol intake alongside candy consumption in the Inter99 cohort. Larsson & Gill (2021) found the protective G allele associated with lower alcohol intake in Mendelian randomization analyses. Ramne et al. (2024) used genetic fine-mapping to show the rs838133 diet signal is distinct from the FGF21 protein pQTL, and that higher circulating FGF21 reduces alcohol intake, suggesting the A allele's effect may partly operate through reduced FGF21 signaling efficiency.

Larsson SC et al. “Genetic Evidence Supporting Fibroblast Growth Factor 21 Signalling as a Pharmacological Target for Cardiometabolic Outcomes and Alzheimer's Disease.” Nutrients (2021)

Allele A

OR —

p —

Candidate gene study

European

Ramne S et al. “Distinct genetic signals at the FGF21 locus complicate studies of FGF21's role in diet regulation using human cohort data.” Molecular Metabolism (2024)

Allele A

OR —

p —

N 157,508

Preliminary work

European

Søberg S et al. “FGF21 Is a Sugar-Induced Hormone Associated with Sweet Intake and Preference in Humans.” Cell Metabolism (2017)

Allele A

OR —

p —

N 6,514

Preliminary work

Danish

Waist-hip ratio

The A allele at rs838133 is paradoxically associated with lower total body-fat percentage but higher waist-hip ratio in 451,099 UK Biobank participants, indicating an unfavorable central fat distribution pattern. This dissociation suggests FGF21 influences not merely total adiposity but the regional partitioning of fat, with A allele carriers accumulating proportionally more abdominal fat. Mendelian randomization evidence from Larsson & Gill (2021) corroborates this, finding the protective G allele favorably associated with waist-to-hip ratio and cardiometabolic markers.

Frayling TM et al. “A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure.” Cell Reports (2018)

Allele A

OR —

p —

N 451,099

Preliminary work

European

Larsson SC et al. “Genetic Evidence Supporting Fibroblast Growth Factor 21 Signalling as a Pharmacological Target for Cardiometabolic Outcomes and Alzheimer's Disease.” Nutrients (2021)

Allele A

OR —

p —

Candidate gene study

European

Blood pressure

The A allele at rs838133 associates with elevated blood pressure in the UK Biobank (n=451,099), representing one of the most prominent cardiometabolic findings beyond dietary phenotypes at this locus. This association is stronger than the variant's effect on BMI or type 2 diabetes, suggesting blood pressure may be a key downstream consequence of FGF21 pathway dysregulation. Larsson & Gill (2021) confirmed via Mendelian randomization that the protective G allele (lower sugar/alcohol intake) associates with favorable blood pressure traits, providing causal support for this relationship.

Frayling TM et al. “A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure.” Cell Reports (2018)

Allele A

OR —

p —

N 451,099

Preliminary work

European

Larsson SC et al. “Genetic Evidence Supporting Fibroblast Growth Factor 21 Signalling as a Pharmacological Target for Cardiometabolic Outcomes and Alzheimer's Disease.” Nutrients (2021)

Allele A

OR —

p —

Candidate gene study

European

Metabolic dysfunction-associated steatohepatitis

A candidate-gene study by Gallego-Durán et al. (2024) found the A allele at rs838133 to be independently associated with MASH (metabolic dysfunction-associated steatohepatitis) and significant hepatic fibrosis in MASLD patients, across both estimation and validation cohorts. The biological rationale is compelling given FGF21's established hepatoprotective role, but the study was small (89 MASLD patients, 44 MASH patients, 28 controls) and requires replication in larger independent cohorts before clinical weight can be assigned.

Gallego-Durán R et al. “Fibroblast growth factor 21 is a hepatokine involved in MASLD progression.” United European Gastroenterology Journal (2024)

Allele A

OR —

p —

N 161

Candidate gene study

European

▶

GWAS Catalog Trait Associations (59)

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

▶

Research that mentions this SNP (1)

▶

Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway: a meta-analysis

Meta-analysisN=34,748McKeown NM et al.(2018)· Diabetologia

Meta-analysis of 34,748 European ancestry adults from 11 CHARGE Consortium cohorts examining sugar-sweetened beverage (SSB) intake associations with glycemic traits. SSB intake was associated with higher fasting glucose (β=0.014 mmol/l, p=1.5×10⁻³) and fasting insulin (β=0.030 log pmol/l, p=2.0×10⁻¹⁰). Although a suggestive interaction between SSB and KLB-rs1542423 was observed in discovery cohorts for fasting insulin (p=0.006), this was not confirmed in replication analysis.

rs838133

Key Literature Trait Associations

Sweet Food Preference

Carbohydrate intake

Alcohol intake

Waist-hip ratio

Blood pressure

Metabolic dysfunction-associated steatohepatitis

GWAS Catalog Trait Associations (59)

Research that mentions this SNP (1)

Community Wiki

Comments