Rs9939609

From SNPedia

rs9939609 is a SNP in the fat mass and obesity associated FTO gene, aka the "Fat Gene" [1]. The original paper describing it is here [PMID 17434869].

[2] The researchers identified 10 different FTO SNPs in the first intron of the gene that associated with both BMI and type-2 diabetes. Because they all correlated with each other, they chose to examine one of the SNPs (rs9939609) in detail.

rs9939609 has also been reported in a large study to be associated with type-2 diabetes. The risk allele (oriented to the dbSNP entry) is (A); the odds ratio associated with heterozygotes is 1.34 (CI 1.17-1.52), and for homozygotes, 1.55 (CI 1.3-1.84). [PMID 17554300]

In a different study, this SNP was found in a linkage block in the FTO gene with rs1121980; see rs1121980 for the association of this block with early onset obesity since it showed the strongest association.[PMID 18159244]

The increases in body mass index associated with rs9939609(A) carriers appears to begin at a young age and are maintained throughout adulthood, according to a study of 5,600+ Utah families.[PMID 18239580]

This SNP did not show any association with obesity, type-2 diabetes or any other related traits in a study of 3,210 Chinese subjects. Furthermore, the minor allele frequency was much lower in Chinese populations compared to populations of European descent.[PMID 17959933]

• 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 18437351] 1,638 type 2 diabetes patients and 1,858 controls

• rs9939609 in FTO (OR 1.14, 95% CI: 1.04-1.25, p = 0.006)

[PMID 18583465] A study of 3,000+ UK children indicated that (A;A) genotypes were less satieted (i.e. had greater appetite) than other genotypes, indicating this risk allele for obesity is likely to influence appetite.

[PMID 18379722] This SNP is also associated with (severe) obesity in a study of 927 Japanese patients.

[PMID 18948966] This SNP may contribute to variation in plasma C-reactive protein (CRP) levels independently of obesity; average CRP levels may be 12-14% higher per rs9939609(A) allele.

[PMID 18719664] This SNP is also associated with adult obesity in Mexicans.

[PMID 19158205] A longitudinal study of Finnish children concluded that the effect of rs9939609 on BMI only becomes evident after age 7, and that the FTO gene is not directly associated with energy intake or physical activity.

[PMID 19214238] Independent of fatness, the A-allele of the FTO SNP appears to increase mortality of a magnitude similar to smoking, but without a particular underlying disease pattern barring an increase in the risk of diseases of the nervous system.

[PMID 18787525] Each copy of the risk-allele A at rs9939609 was significantly associated with 0.45 kg/m(2) increase in BMI (95% confidence interval (CI): 0.16-0.74; P = 0.004) and 0.97 cm increase in waist circumference (95% CI: 0.21-0.65; P = 0.0002). Similar results were observed for rs8050136. may confer a modest susceptibility to obesity in an ethnicity-specific manner, but may be unlikely to contribute to a clinically significant diabetes risk.

GWAS
SNP	rs9939609
PubMedID	[PMID 17434869]
Condition	Body mass index
Gene	FTO
Risk Allele	A
pValue	2.00E-020
OR	0.36
95% CI	NR) kg/m2 per copy in adult

[PMID 18839134] Assessing gene-treatment interactions at the FTO and INSIG2 loci on obesity-related traits in the Diabetes Prevention Program

[PMID 18855084] The FTO obesity gene. Genotyping and gene expression analysis in morbidly obese patients

[PMID 19265514] FTO gene variation and measures of body mass in an African population

GWAS snp
PMID	[PMID 19079261]
Trait	Body mass index
Title	Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
Risk Allele	A
P-val	4E-51
Odds Ratio	0.33 [0.27-0.39] kg/m2 increase

GWAS snp
PMID	[PMID 19396169]
Trait	Biomedical quantitative traits
Title	A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits
Risk Allele	A
P-val	2E-7
Odds Ratio	0.24 [0.14-0.32] kg/m2 increase

[PMID 19322589] Analysis of FTO gene variants with measures of obesity and glucose homeostasis in the IRAS Family Study

[PMID 19587359] Regulation and function of FTO mRNA expression in human skeletal muscle and subcutaneous adipose tissue

[PMID 19687793] Macronutrient-specific effect of FTO rs9939609 in response to a 10-week randomized hypo-energetic diet among obese Europeans

[PMID 19726594] Fat and carbohydrate intake modify the association between genetic variation in the FTO genotype and obesity

[PMID 19793853] Postprandial responses in hunger and satiety are associated with the rs9939609 single nucleotide polymorphism in FTO

[PMID 19828706] The FTO gene rs9939609 obesity-risk allele and loss of control over eating

[PMID 19859840] Association of the common rs9939609 variant of FTO gene with polycystic ovary syndrome in Chinese women

[PMID 20031593] The FTO Gene Is Associated With an Atherogenic Lipid Profile and Myocardial Infarction in Patients With Type 2 Diabetes: A Genetics of Diabetes Audit and Research Study in Tayside Scotland (Go-DARTS) Study

[PMID 20051647] Association of the Common Fat Mass and Obesity Associated (FTO) Gene Polymorphism with Obesity in a Japanese Population

[PMID 20075932] Association of gene polymorphism of the fat-mass and obesity-associated gene with insulin resistance in Japanese

[PMID 20090391] Effects of the FTO Gene on Lifestyle Intervention Studies in Children

[PMID 20092643] Large effects on body mass index and insulin resistance of fat mass and obesity associated gene (FTO) variants in patients with polycystic ovary syndrome (PCOS)

[PMID 20181787] A Variant in the Fat Mass and Obesity-Associated Gene (FTO) and Variants near the Melanocortin-4 Receptor Gene (MC4R) Do Not Influence Dietary Intake

[PMID 20186840] A genetic variation in the fat mass- and obesity-associated gene is associated with obesity and newly diagnosed type 2 diabetes in a Chinese population