Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.

Domain Wall Propagation in Meso and Nanoscale Ferroelectrics

As part of an ongoing programme to evaluate the extent to which external morphology alters domain wall mobility in ferroelectrics, the electrical switching characteristics of single-crystal BaTiO3 nanorods and thin film plates have been measured and compared. It was found that ferroelectric nanorods were more readily switched than thin plates; increasing the shape constraint therefore appears to enhance switchability. This observation is broadly consistent with previous work, in which local notches patterned along the length of nanorods enhanced switching (McMillen et al 2010 Appl. Phys. Lett. 96 042904), while antinotches had the opposite effect (McQuaid et al 2010 Nano Lett. 10 3566). In this prior work, local enhancement and denudation of the electric field was expected at the notch and antinotch sites, respectively, and this was thought to be the reason for the differences in switching behaviour observed. However, for the simple nanorods and plates investigated here, no differences in the electric field distributions are expected. To rationalise the functional measurements, domain development during switching was imaged directly by piezoresponse force microscopy. A two-stage process was identified, in which narrow needle-like reverse domains initially form across the entire interelectrode gap and then subsequently coarsen through domain wall propagation perpendicular to the applied electric field. To be consistent with the electrical switching data, we suggest that the initial formation of needle domains occurs more readily in the nanorods than in the plates.