rs1421085
| obesity risk |
| Orientation | plus |
| Stabilized | plus |
| Geno | Mag | Summary |
|---|---|---|
| (C;C) | 3.1 | ~1.7x increased obesity risk |
| (C;T) | 2.5 | ~1.3x increased obesity risk |
| (T;T) | 0.1 | normal obesity risk |
| Reference | GRCh38 38.1/141 |
| Chromosome | 16 |
| Position | 53767042 |
| Gene | FTO |
| is a | snp |
| is | mentioned by |
| dbSNP | rs1421085 |
| dbSNP (classic) | rs1421085 |
| ClinGen | rs1421085 |
| ebi | rs1421085 |
| HLI | rs1421085 |
| Exac | rs1421085 |
| Gnomad | rs1421085 |
| Varsome | rs1421085 |
| LitVar | rs1421085 |
| Map | rs1421085 |
| PheGenI | rs1421085 |
| Biobank | rs1421085 |
| 1000 genomes | rs1421085 |
| hgdp | rs1421085 |
| ensembl | rs1421085 |
| geneview | rs1421085 |
| scholar | rs1421085 |
| rs1421085 | |
| pharmgkb | rs1421085 |
| gwascentral | rs1421085 |
| openSNP | rs1421085 |
| 23andMe | rs1421085 |
| SNPshot | rs1421085 |
| SNPdbe | rs1421085 |
| MSV3d | rs1421085 |
| GWAS Ctlg | rs1421085 |
| GMAF | 0.2479 |
| Max Magnitude | 3.1 |
| ? | (C;C) (C;T) (T;T) | 28 |
|---|---|---|
|
| ||
rs1421085 is a SNP located in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16. This SNP showed the most association with obesity in the original work by Dina et al [PMID 17496892].
[PMID 26287746
] The rs1421085 T-to- C single-nucleotide alteration underlies the association between FTO and obesity by disrupting ARID5B-mediated repression of IRX3 and IRX5. This disruption leads to a developmental shift from browning to whitening programs and loss of mitochondrial thermogenesis
Within the FTO gene, many SNPs appear to be co-inherited. The SNP showing the strongest association with body weight (i.e. body mass index, BMI) is not rs1421085, although this SNP is one of co-inherited SNPs in the FTO gene region. For more information, refer to the FTO gene or the most studied of FTO SNPs, rs9930506. [PMID 17658951]
However, in one study of 583 extremely obese women with several FTO SNPs, the strongest association was indeed with rs1421085 (p=3.04x10-10, OR = 1.75, CI: 1.47-2.08).[PMID 18218107]
- Note: The three FTO SNPs, rs1421085, rs17817449, and rs9939609, are in strong linkage disequilibrium (pairwise r2>0.97), and there are two primary haplotypes, C-G-A (42.0 %) and T-T-T (55.5 %).
[PMID 18719664] This SNP is also associated with adult obesity in Mexicans.
[PMID 19153581] rs17782313(C) more snacking, however rs1421085(C) did not influence eating behavior
[PMID 18551112] rs1421085(C) and rs17817449(G) significantly associated with increased BMI. Our results suggest that FTO may be one of the worldwide obesity-risk genes.
| GWAS snp | |
|---|---|
| PMID | [PMID 19151714] |
| Trait | Obesity |
| Title | Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations |
| Risk Allele | C |
| P-val | 1E-28 |
| Odds Ratio | 1.39 [1.27-1.51] |
[PMID 19322589] Analysis of FTO gene variants with measures of obesity and glucose homeostasis in the IRAS Family Study
[PMID 19818665] Apolipoprotein E genotype is associated with serum C-reactive protein but not abdominal aortic aneurysm
[PMID 20373279] FTO Genotype and Weight Gain in Obese and Normal Weight Adults From a Norwegian Population Based Cohort (the HUNT Study)
[PMID 20502638] Risk of Type 2 Diabetes and Obesity Is Differentially Associated with Variation in FTO in Whites and African-Americans in the ARIC Study
[PMID 21248310] Examining Overweight and Obesity as Risk Factors for Common Mental Disorders Using Fat Mass and Obesity-Associated (FTO) Genotype-Instrumented Analysis: The Whitehall II Study, 1985-2004
[PMID 21796137] Association of variations in the FTO, SCG3 and MTMR9 genes with metabolic syndrome in a Japanese population
[PMID 22590636] Prevalence and Determinants of Metabolic Syndrome among Women in Chinese Rural Areas
[PMID 17928949] FTO polymorphisms in oceanic populations.
[PMID 18159244] Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants.
[PMID 18379722] Variations in the FTO gene are associated with severe obesity in the Japanese.
[PMID 18487448] Common variation in the fat mass and obesity-associated (FTO) gene confers risk of obesity and modulates BMI in the Chinese population.
[PMID 18572014] FTO gene associates to metabolic syndrome in women with polycystic ovary syndrome.
[PMID 18599522] FTO variants are associated with obesity in the Chinese and Malay populations in Singapore.
[PMID 18647953] Fat mass-and obesity-associated (FTO) gene variant is associated with obesity: longitudinal analyses in two cohort studies and functional test.
[PMID 19079261] Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.
[PMID 19255736] Combined effects of MC4R and FTO common genetic variants on obesity in European general populations.
[PMID 19557161] Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
[PMID 20075150] Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study.
[PMID 20080751] Long-range gene regulation links genomic type 2 diabetes and obesity risk regions to HHEX, SOX4, and IRX3.
[PMID 20127379] From monogenic to polygenic obesity: recent advances.
[PMID 20381893] The genetics of obesity: FTO leads the way.
[PMID 20404173] A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly.
[PMID 20421936] Two new Loci for body-weight regulation identified in a joint analysis of genome-wide association studies for early-onset extreme obesity in French and german study groups.
[PMID 20442772] Common SNPs in FTO gene are associated with obesity related anthropometric traits in an island population from the eastern Adriatic coast of Croatia.
[PMID 20703240] Polymorphisms in NRXN3, TFAP2B, MSRA, LYPLAL1, FTO and MC4R and their effect on visceral fat area in the Japanese population.
[PMID 21102551] Analysis of FTO gene variants with obesity and glucose homeostasis measures in the multiethnic Insulin Resistance Atherosclerosis Study cohort.
[PMID 21283731] FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome.
[PMID 21317302] FTO polymorphisms are associated with adult body mass index (BMI) and colorectal adenomas in African-Americans.
[PMID 21318054] Rs9939609 variant of the fat mass and obesity-associated gene and trunk obesity in adolescents.
[PMID 22187296] Variants of the FTO gene in obese children and their impact on body composition and metabolism before and after lifestyle intervention.
[PMID 22189543] Genetic variants in FTO associated with metabolic syndrome: a meta- and gene-based analysis.
[PMID 22513296] Obesity susceptibility loci and dietary intake in the Look AHEAD Trial.
[PMID 23136261] Fat mass and obesity gene and cognitive decline: The Atherosclerosis Risk in Communities Study
[PMID 23342142] Association of FTO Polymorphisms with Obesity and Obesity-Related Outcomes in Portuguese Children.
[PMID 23341774] A Systematic Mapping Approach of 16q12.2/FTO and BMI in More Than 20,000 African Americans Narrows in on the Underlying Functional Variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) Study
| GWAS snp | |
|---|---|
| PMID | [PMID 23636237]
|
| Trait | Dietary macronutrient intake |
| Title | Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake. |
| Risk Allele | C |
| P-val | 1E-9 |
| Odds Ratio | .10 [0.061-0.139] % increase |
[PMID 24106974] Association between fat mass and obesity-associated (FTO) gene and hip fracture susceptibility
| GWAS snp | |
|---|---|
| PMID | [PMID 23563607]
|
| Trait | Obesity |
| Title | Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. |
| Risk Allele | C |
| P-val | 6E-39 |
| Odds Ratio | 1.45 [NR] |
| GWAS snp | |
|---|---|
| PMID | [PMID 23563609]
|
| Trait | Obesity (early onset extreme) |
| Title | Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity. |
| Risk Allele | C |
| P-val | 3E-28 |
| Odds Ratio | 1.44 [1.35-1.54] |
[PMID 24348519] EMR-linked GWAS study: investigation of variation landscape of loci for body mass index in children
[PMID 22761283] Multigene interactions and the prediction of depression in the Wisconsin Longitudinal Study.
[PMID 22801903] Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome: a systematic review and meta-analysis.
[PMID 23849767] Effects of FTO RS9939906 and MC4R RS17782313 on obesity, type 2 diabetes mellitus and blood pressure in patients with hypertension.
[PMID 24863145] FTO genotype and aging: pleiotropic longitudinal effects on adiposity, brain function, impulsivity and diet
“Genetic associations with traits in 23andMe customers.” 23andMe White Paper.
[PMID 25074273] Association of obesity with rs1421085 and rs9939609 polymorphisms of FTO gene
[PMID 26935496] The Frequencies of Haplotypes of FTO Gene Variants and Their Association with the Distribution of Body Fat in Non-Obese Poles.
| ClinVar | |
|---|---|
| Risk | Rs1421085(C;C) |
| Alt | Rs1421085(C;C) |
| Reference | Rs1421085(T;T) |
| Significance | Other |
| Disease | OBESITY (BMIQ14) |
| Variation | info |
| Gene | FTO |
| CLNDBN | OBESITY (BMIQ14), SUSCEPTIBILITY TO |
| Reversed | 0 |
| HGVS | NC_000016.9:g.53800954T>C |
| CLNSRC | OMIM Allelic Variant |
| CLNACC | RCV000201907.1, |
[PMID 28451524] Fat Mass and Obesity Associated Gene Polymorphism and the Risk of Polycystic Ovary Syndrome: A Meta-analysis.
[PMID 28585683] The age of developing diabetes and FTO polymorphisms (rs9939609, rs1421085, and rs9930506).
[PMID 29466028] Analysis of the Impact of Common Polymorphisms of the FTO and MC4R Genes with the Risk of Severe Obesity in Saudi Arabian Population.
[PMID 30091126] Association of type 2 diabetes susceptible genes GCKR, SLC30A8, and FTO polymorphisms with gestational diabetes mellitus risk: a meta-analysis.
[PMID 30124167] A fat mass and obesity-associated gene polymorphism influences fat mass in exercise-trained individuals.
[PMID 30496407] Bidirectional Mendelian randomization to explore the causal relationships between body mass index and polycystic ovary syndrome.
[PMID 30537186] Genetic variation of FTO: rs1421085 T>C, rs8057044 G>A, rs9939609 T>A, and copy number (CNV) in Mexican Mayan school-aged children with obesity/overweight and with normal weight.
[PMID 30822753] Effects of fat mass and obesity-associated (FTO) gene polymorphisms on binge eating in women with binge-eating disorder: The moderating influence of attachment style.
[PMID 30871540] FTO haplotyping underlines high obesity risk for European populations.
[PMID 32076432] FTO Variant rs1421085 Associates With Increased Body Weight, Soft Lean Mass, and Total Body Water Through Interaction With Ghrelin and Apolipoproteins in Arab Population.
[PMID 32316277] FTO Intronic SNP Strongly Influences Human Neck Adipocyte Browning Determined by Tissue and PPARγ Specific Regulation: A Transcriptome Analysis.
[PMID 32874676] Differences in brain structure and function in children with the FTO obesity-risk allele.
