Genome-Wide Association Study of Multiple Sclerosis Confirms a Novel Locus at 5p13.1

Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80–0.89; p = 1.36×10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS

Analogue models of the effect of long-term basement fault movement on volcanic edifices

Long-term fault movement under volcanoes can control the edifice structure and can generate collapse events. To study faulting effects, we explore a wide range of fault geometries and motions, from normal, through vertical to reverse and dip-slip to strike-slip, using simple analogue models. We explore the effect of cumulative sub-volcanic fault motions and find that there is a strong influence on the structural evolution and potential instability of volcanoes. The variety of fault types and geometries are tested with realistically scaled displacements, demonstrating a general tendency to produce regions of instability parallel to fault strike, whatever the fault motion. Where there is oblique-slip faulting, the instability is always on the downthrown side and usually in the volcano flank sector facing the strike-slip sense of motion. Different positions of the fault beneath the volcano change the location, type and magnitude of the instability produced. For example, the further the fault is from the central axis, the larger the destabilised sector. Also, with greater fault offset from the central axis larger unstable volumes are generated. Such failures are normal to fault strike. Using simple geometric dimensionless numbers, such as the fault dip, degree of oblique motion (angle of obliquity), and the fault position, we graphically display the geometry of structures produced. The models are applied to volcanoes with known underlying faults, and we demonstrate the importance of these faults in determining volcanic structures and slope instability. Using the knowledge of fault patterns gained from these experiments, geological mapping on volcanoes can locate fault influence and unstable zones, and hence monitoring of unstable flanks could be carried out to determine the actual response to faulting in specific cases