rs35859249

Also known as the R125W variant, rs35859249 is a SNP in the TBC1D1 gene that has been associated with familiar - but not nonfamilial - obesity in several studies. The (C) allele encodes the (R), arginine, and the (T) allele encodes the (W), tryptophan. In the first study to be published about this SNP, an analysis of primarily Utah families with obesity implicated the rs35859249(T) allele as a predisposing factor. This allele segregated with affected females in a majority of the chromosome 4p15–14-linked obesity-prone pedigrees, was enriched on disease-associated haplotypes (P=0.000007), accounted for the majority of the linkage evidence at 4p15–14, and appeared to be the causal variant. This study also implied a gene-gene interaction including another obesity predisposition locus further down the same chromosome at 4q34–35. Subsequently, a study of 9,714 French Caucasian individuals, combining family-based and general population studies, confirmed an association with familial obesity, yet did not find any association with body mass index or obesity in a large population-based cohort.