rs1121980

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This is a intron variant variant in the FTO gene.

Key Literature Trait Associations

Obesity Risk

Each copy of the T allele at rs1121980 in intron 1 of FTO is associated with a ~20% increased odds of obesity. This variant is in strong linkage disequilibrium with rs9939609, the lead FTO obesity signal identified in a GWAS of 38,759 participants. The FTO intronic risk haplotype influences BMI through altered regulation of nearby genes including IRX3 and IRX5.

“FTO gene polymorphisms and obesity risk: a meta-analysis”
Allele T
OR 1.34
p 1.0e-7
N 111,571
Meta-analysisSmall GWAS
multi-ancestry
Frayling TM et al. “A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity.” Science (new York, N.y.) 316(5826):889-894 (2007)
Allele T
OR 1.20
p 5.0e-8
Preliminary work
“Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry”
Allele T
OR —
p 3.0e-3
N 111,421
Preliminary work
European
“FTO genetic variation and association with obesity in West Africans and African Americans”
Allele T
OR —
p —
N 1,485
Preliminary work
African American and West African

Body mass index

The rs1121980 A allele is associated with higher BMI in large population studies. In a European prospective cohort of 20,374 adults, each A allele conferred a 0.31 BMI-unit increase (p<0.001) and a 0.77 cm wider waist circumference. This effect was substantially larger in physically inactive individuals (0.44 BMI units/allele) versus active individuals (0.25 BMI units/allele; interaction p=0.004). GWAS Catalog data report a beta of ~0.06 SD at genome-wide significance (p=4×10⁻⁸), consistent with the variant's well-established modest but highly replicated BMI effect across cohorts.

Vimaleswaran KS et al. “Physical activity attenuates the body mass index-increasing influence of genetic variation in the FTO gene.” The American Journal of Clinical Nutrition (2009)
Allele A
OR —
β 0.310
p 1.0e-3
N 20,374
Preliminary work
European
“Obesity-susceptibility loci have a limited influence on birth weight: a meta-analysis of up to 28,219 individuals”
Allele A
OR —
p —
N 28,219
Meta-analysis
European

Blood glucose

GWAS Catalog data show rs1121980 A allele is associated with higher fasting blood glucose (beta=0.0164 mmol/L, p=1×10⁻²⁰), reaching genome-wide significance in large metabolic trait studies. This association may be partly mediated through the variant's effect on adiposity and insulin resistance, as FTO locus SNPs in high LD influence glucose homeostasis. The effect is modest in absolute terms but highly significant given the large sample sizes of metabolic GWAS consortia (e.g., MAGIC consortium datasets).

Scott RA et al. “Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.” Nature Genetics (2012)
Allele A
OR —
β 0.016
p 1.0e-20
N 133,010
Large GWAS
European

Leptin levels

The rs1121980 A allele is associated with higher circulating leptin levels (beta=0.075 SD, p=1×10⁻¹⁵ per GWAS Catalog). This is likely partly mediated through the variant's effect on fat mass, since leptin is secreted by adipocytes proportional to body fat. The genome-wide significant association with leptin reinforces the biological link between the FTO locus and adipokine signalling pathways relevant to energy balance regulation.

Kilpeläinen TO et al. “Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.” Nature Communications 7:10494 (2016)
Allele A
OR —
β 0.075
p 1.0e-15
N 32,161
Major Consortium StudyLarge GWAS
European

Age at puberty

GWAS Catalog data report an association between rs1121980 G allele and earlier puberty onset (beta=0.0217 years earlier, p=3×10⁻¹¹) in large consortium studies of puberty timing. This is biologically plausible given FTO's established role in fat mass and the well-known link between adiposity and earlier pubertal development, particularly in girls. The effect size is small but the signal is genome-wide significant in studies with large sample sizes.

Perry JR et al. “Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.” Nature 514(7520):92-97 (2014)
Allele G
OR —
β 0.022
p 3.0e-11
N 182,416
Large GWAS
European

HDL cholesterol

GWAS Catalog data report the rs1121980 A allele is associated with lower HDL cholesterol (beta=−0.02 SD, p=7×10⁻⁹), reaching genome-wide significance in large lipid GWAS. The effect is modest but consistent with the broader metabolic consequences of FTO locus variation, including increased adiposity and associated dyslipidaemia. Reduced HDL in A-allele carriers has also been observed in smaller clinical studies of obese individuals.

Willer CJ et al. “Discovery and refinement of loci associated with lipid levels.” Nature Genetics 45(11):1274-1283 (2013)
Allele A
OR —
β -0.020
p 7.0e-9
N 188,577
Large GWAS
European

Triglyceride levels

The rs1121980 A allele is associated with higher fasting triglyceride levels (beta=0.021 mg/dL SD, p=3×10⁻⁸) at genome-wide significance per GWAS Catalog data, consistent with the metabolic dyslipidaemia profile associated with higher adiposity at the FTO locus. This effect mirrors the broader pattern of the FTO risk allele promoting unfavourable metabolic traits across multiple lipid and glucose parameters.

Willer CJ et al. “Discovery and refinement of loci associated with lipid levels.” Nature Genetics 45(11):1274-1283 (2013)
Allele A
OR —
β 0.021
p 3.0e-8
N 188,577
Large GWAS
European
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GWAS Catalog Trait Associations (11)

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

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Research that mentions this SNP (4)

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Genetic variation of FTO: rs1421085 T&gt;C, rs8057044 G&gt;A, rs9939609 T&gt;A, and copy number (CNV) in Mexican Mayan school‐aged children with obesity/overweight and with normal weight
ReviewLizbeth González‐Herrera et al.(2019)· American Journal of Human Biology

A literature review of 70 studies examining single nucleotide polymorphisms (SNPs) associated with obesity in Mexican populations published 2011-2021. The authors identified SNPs with differential behavior in Mexican compared to Caucasian populations, including rs17782313 (MC4R), rs6548238 (TMEM18), rs6265 (BDNF), rs7498665 (SH2B1), and notably rs6232 (PCSK1) associated with early-onset obesity in Mexican youth. The review emphasizes ethnicity-dependent genetic effects on BMI heritability (40-70%) and highlights genes involved in cholesterol metabolism and adipokine signaling pathways.

Traits studied:AdiposityBlood pressureBody mass index (BMI)Cardiovascular risk factorsDyslipidemiaInsulin resistanceMetabolic syndromeObesityOverweightType 2 diabetes
PubMedDOIMetascience Observatory
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Associations of polymorphisms in the genes of FGFR2, FGF1, and RBFOX2 with breast cancer risk by estrogen/progesterone receptor status
AssociationN=2,416Yu‐Ling Cen et al.(2013)· Molecular Carcinogenesis

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

Traits studied:Breast cancerBreast cancer riskER+/PR+ breast cancerER/PR negative breast cancerTriple negative breast cancer
PubMedDOIMetascience Observatory
▶
Susceptibility variants for obesity and colorectal cancer risk: The multiethnic cohort and PAGE studies
AssociationN=11,673Unhee Lim et al.(2012)· International Journal of Cancer

This case-control study of 2,033 colorectal cancer cases and 9,640 controls investigated whether BMI and waist size susceptibility variants are associated with colorectal cancer risk. Two obesity SNPs showed significant associations: KCTD15 rs29941 (OR = 0.90, p = 0.01) was protective, while MC4R rs17782313 (OR = 1.12, p = 0.02) increased risk. However, neither association remained significant after multiple comparisons correction, and overall obesity variants showed minimal effects on colorectal cancer.

Traits studied:Body mass index (BMI)Colorectal cancerWaist size
PubMedDOIMetascience Observatory
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Analysis of FTO gene variants with measures of obesity and glucose homeostasis in the IRAS Family Study
AssociationN=2,028Maria R. Wing et al.(2009)· Human Genetics

Analysis of 27 FTO gene variants in 1,424 Hispanic Americans and 604 African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS) found multiple SNPs associated with BMI, waist circumference, and subcutaneous adipose tissue (p-values 0.001-0.05 in Hispanics), confirming FTO's role in overall fat mass rather than visceral fat distribution. Key variants rs9939609, rs8050136, rs1121980, rs1421085, rs17817449, and rs3751812 showed consistent associations with adiposity measures, with effect sizes of 0.3-2.4 kg/m² per allele for BMI in Hispanic Americans.

Traits studied:Acute insulin responseBody mass index (BMI)Disposition indexFasting glucoseFasting insulinInsulin sensitivityObesitySubcutaneous adipose tissue (SAT)Visceral adipose tissue (VAT)Waist circumferenceWaist-hip ratio (WHR)
PubMedDOIMetascience Observatory

Gene information from NCBI Gene. Variant classifications from ClinVar.

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