Unraveling the Function of FTO Variants

Body-mass index (BMI), which represents a complex trait with high heritability, is a clinically relevant surrogate for obesity.1 Genomewide association studies have identified nearly 10,000 genetic polymorphisms in single-nucleotide variants (SNVs) associated with various human disorders and traits. However, approximately 90% of these variants are in genomic regions that do not map to coding regions and, therefore, do not directly affect protein synthesis or translation.2 However, risk-associated loci containing noncoding variants can alter gene expression by modulating the activity of neighboring cis-regulatory elements — that is, noncoding DNA sequences in or near a gene that can modify the expression . . .