rs1421085

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 . 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. 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). * Note: The three FTO SNPs, rs1421085, rs17817449, and rs9939609, are in strong linkage disequilibrium (pairwise r 2 >0.97), and there are two primary haplotypes, C-G-A (42.0 %) and T-T-T (55.5 %). This SNP is also associated with adult obesity in Mexicans. rs17782313(C) more snacking, however rs1421085(C) did not influence eating behavior rs1421085(C) and rs17817449(G) significantly associated with increased BMI. Our results suggest that FTO may be one of the worldwide obesity-risk genes. “Genetic associations with traits in 23andMe customers.” 23andMe White Paper.