Rs9939609

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

[PMID 20337217] FTO polymorphisms are associated with obesity but not with diabetes in East Asian populations: a meta-analysis

[PMID 20377915] FTO variant rs9939609 is associated with body mass index and waist circumference, but not with energy intake or physical activity in European- and African- American youth

[PMID 20400278] Association of the FTO gene variant (rs9939609) with cardiovascular disease in men with abnormal glucose metabolism - The Finnish Diabetes Prevention Study

[PMID 20467478] The Common FTO Genetic Polymorphism rs9939609 is Associated with Increased BMI in Type 1 Diabetes but not with Diabetic Nephropathy

[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 20512162] The obesity-associated SNPs in intron 1 of the FTO gene affect primary transcript levels

[PMID 20511725] No association of obesity gene FTO with body composition at the age of 6 months. The Generation R Study

[PMID 20650268] Effects of common FTO gene variants associated with BMI on dietary intake and physical activity in Korean

[PMID 20702506] Life-Course Analysis of a Fat Mass and Obesity-Associated (FTO) Gene Variant and Body Mass Index in the Northern Finland Birth Cohort 1966 Using Structural Equation Modeling

[PMID 20811910] FTO influences on longitudinal BMI over childhood and adulthood and modulation on relationship between birth weight and longitudinal BMI

[PMID 20858286] Variant rs9939609 in the FTO gene is associated with body mass index among Chinese children

[PMID 20948226] Gene Expression of FTO in Human Subcutaneous Adipose Tissue, Peripheral Blood Mononuclear Cells and Adipocyte Cell Line

[PMID 20966902] Genome-Wide Association Study of Anthropometric Traits and Evidence of Interactions With Age and Study Year in Filipino Women

[PMID 21134343] Variants in the fat mass and obesity associated (FTO) gene are associated with obesity and C-reactive protein levels in Chinese Han populations

[PMID 21186106] Education modulates the association of the FTO rs9939609 polymorphism with body mass index and obesity risk in the Mediterranean population

[PMID 21246032] Influences of the Common FTO rs9939609 Variant on Inflammatory Markers Throughout a Broad Range of Body Mass Index

[PMID 20057365] Meta-analysis added power to identify variants in FTO associated with type 2 diabetes and obesity in the Asian population

GWAS snp
PMID	[PMID 21102462]
Trait
Title	Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
Risk Allele	A
P-val	3E-8
Odds Ratio	2.1000 [1.32-2.88] week decrease

[PMID 21318054] variant of the fat mass and obesity-associated gene and trunk obesity in adolescents.

[PMID 21411553] Associations between a Single Nucleotide Polymorphism of the FTO Gene (rs9939609) and Obesity-Related Characteristics over Time during Puberty in a Dutch Children Cohort

[PMID 21443588] Association between the FTO gene and overweight in Japanese children and adolescents

[PMID 21637715] Detailed Analysis of Variants in FTO in Association with Body Composition in a Cohort of 70-Year-Olds Suggests a Weakened Effect among Elderly

[PMID 21720422] Differences in the Heritability of Growth and Growth Velocity During Infancy and Associations With FTO Variants

[PMID 21741858] The rs7204609 Polymorphism in the Fat Mass and Obesity-Associated Gene is Positively Associated With Central Obesity and Microalbuminuria in Patients With Type 2 Diabetes From Southern Brazil

[PMID 21796137] Association of variations in the FTO, SCG3 and MTMR9 genes with metabolic syndrome in a Japanese population

[PMID 21798115] Dietary fatty acid distribution modifies obesity risk linked to the rs9939609 polymorphism of the fat mass and obesity-associated gene in a Spanish case-control study of children

[PMID 21818152] Polymorphisms in the NPY2R Gene Show Significant Associations With BMI That Are Additive to FTO, MC4R, and NPFFR2 Gene Effects

[PMID 21842748] [The study of polymorphism rs9939609 FTO gene in patients with overweight and obesity]

[PMID 21913894] rs9939609 in the FTO Gene is Associated with Obesity but not with Several Biochemical Parameters in Sardinian Obese Children

[PMID 21868005] Variations in the fat mass and obesity-associated (FTO) gene are related to glucose levels and higher lipid accumulation product in postmenopausal women from southern Brazil

[PMID 21986706] The association of variants in the FTO gene with longitudinal body mass index profiles in non-Hispanic white children and adolescents

[PMID 21989907] Association of the FTO rs9939609 polymorphism with obesity in roma/gypsy population

[PMID 21673421] Genetic factors in risk assessment for the development of type 2 diabetes mellitus in a small case series

[PMID 22030988] FTO Risk Haplotype Among Early Onset and Severe Obesity Cases in a Population of Western Spain

[PMID 22051089] Associations of Obesity Genes with Obesity-related Outcomes in Multiethnic Children

[PMID 22069379] Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children

[PMID 22090522] PS2-41: The FTO Gene, Its Variants and Post-menopausal Breast Cancer

[PMID 22132335] An Obesity-Related FTO Variant and the Risk of Preeclampsia in a Finnish Study Population

[PMID 22141579] FTO gene is related to obesity in Chilean Amerindian children and impairs HOMA-IR in prepubertal girls

[PMID 21749608] Genetic variants and the metabolic syndrome: a systematic review

[PMID 22189607] Associations of the FTO rs9939609 variant with discrete body fat depots and dietary intake in a multi-ethnic cohort

[PMID 22234326] Genome wide analysis reveals association of a FTO gene variant with epigenetic changes

[PMID 22391885] Variations in the obesity genes FTO, TMEM18 and NRXN3 influence the vulnerability of children to weight gain induced by short sleep duration

[PMID 22421923] Associations of variants in FTO and near MC4R with obesity traits in South Asian Indians

[PMID 22421893] Association Between FTO Variant and Change in Body Weight and Its Interaction With Dietary Factors: The DiOGenes Study