Rs9939609

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

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).

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.

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.

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.


 * 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 %).

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)

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.

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

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.

This SNP is also associated with adult obesity in Mexicans.

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.

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.

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.