Abstract Context Genome-wide association studies have identified >450 single nucleotide polymorphisms (SNPs) for type 2 diabetes (T2D). Objective To facilitate use of these SNPs in future genetic risk score (GRS)-based analyses, we aimed to classify the SNPs based on physiology. We also sought to validate GRS associations with insulin-related traits in deeply-phenotyped Mexican Americans. Design, Setting, and Participants 457 T2D SNPs from the literature were assigned physiologic function based on association studies and cluster analyses....

Modern humans have more fragile skeletons than other hominins, which may result from physical inactivity. Here we test whether reproductive effort also compromises bone strength, by measuring using computed tomography thoracic vertebral bone mineral density (BMD) and fracture prevalence among physically active Tsimane forager-horticulturalists. Earlier onset of reproduction and shorter interbirth intervals are associated with reduced BMD for women. Tsimane BMD is lower versus Americans, but only for women, contrary to simple predictions relying on...