Structural forms of the human amylase locus and their relationships to SNPs, haplotypes and obesity

Abstract

Steven McCarroll, Joel Hirschhorn and colleagues identify eight common structural forms of the human amylase locus. They measured amylase gene copy number in ~3,500 individuals and detected no association with BMI and obesity. Hundreds of genes reside in structurally complex, poorly understood regions of the human genome1,2,3. One such region contains the three amylase genes (AMY2B, AMY2A and AMY1) responsible for digesting starch into sugar. Copy number of AMY1 is reported to be the largest genomic influence on obesity4, although genome-wide association studies for obesity have found this locus unremarkable. Using whole-genome sequence analysis3,5, droplet digital PCR6 and genome mapping7, we identified eight common structural haplotypes of the amylase locus that suggest its mutational history. We found that the AMY1 copy number in an individual's genome is generally even (rather than odd) and partially correlates with nearby SNPs, which do not associate with body mass index (BMI). We measured amylase gene copy number in 1,000 obese or lean Estonians and in 2 other cohorts totaling ∼3,500 individuals. We had 99% power to detect the lower bound of the reported effects on BMI4, yet found no association.