A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.     

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.     

A belt of moonlets in Saturn's A ring

The origin and evolution of planetary rings is one of the prominent unsolved problems of planetary sciences, with direct implications for planet-forming processes in pre-planetary disks. The recent detection of four propeller-shaped features in Saturn's A ring proved the presence of large boulder-sized moonlets in the rings. Their existence favours ring creation in a catastrophic disruption of an icy satellite rather than a co-genetic origin with Saturn, because bodies of this size are unlikely to have accreted inside the rings. Here we report the detection of eight new propeller features in an image sequence that covers the complete A ring, indicating embedded moonlets with radii between 30 m and 70 m. We show that the moonlets found are concentrated in a narrow 3,000-km-wide annulus 130,000 km from Saturn. Compared to the main population of ring particles (radius s < 10 m), such embedded moonlets have a short lifetime with respect to meteoroid impacts. Therefore, they are probably the remnants of a shattered ring-moon of Pan size or larger, locally contributing new material to the older ring. This supports the theory of catastrophic ring creation in a collisional cascade.