Common variants in left/right asymmetry genes and pathways are associated with relative hand skill

Humans display structural and functional asymmetries in brain organization, strikingly with respect to language and handedness. The molecular basis of these asymmetries is unknown. We report a genome-wide association study meta-analysis for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)] (n = 728). The most strongly associated variant, rs7182874 (P = 8.68×10-9), is located in PCSK6, further supporting an association we previously reported. We also confirmed the specificity of this association in individuals with RD; the same locus was not associated with relative hand skill in a general population cohort (n = 2,666). As PCSK6 is known to regulate NODAL in the development of left/right (LR) asymmetry in mice, we developed a novel approach to GWAS pathway analysis, using gene-set enrichment to test for an over-representation of highly associated variants within the orthologs of genes whose disruption in mice yields LR asymmetry phenotypes. Four out of 15 LR asymmetry phenotypes showed an over-representation (FDR≤5%). We replicated three of these phenotypes; situs inversus, heterotaxia, and double outlet right ventricle, in the general population cohort (FDR≤5%). Our findings lead us to propose that handedness is a polygenic trait controlled in part by the molecular mechanisms that establish LR body asymmetry early in development. © 2013 Brandler et al.

The effect of supporting a surgeon's wrist on their hand tremor

Background. Operative tremor can greatly influence the outcome of certain, precise, microsurgical operations. Reducing a surgeons tremor may not only improve the operative results but decrease the operative time. Previous studies have only measured uni or bi directional tremor and therefore have been unable to calculate both the overall tremor amplitude and the tremor reduction by resting the wrists. Materials and methods. We measured the tremor of 21 neurologically normal volunteers while performing a micromanipulation task, with and without wrist support. Measurements were acquired in three dimensions using three accelerometers attached to the hand, allowing an overall tremor amplitude to be calculated. Results. Resting the wrist on a gelled surface decreases an individuals tremor by a factor of 2.67 (P = 0). Conclusions. Supporting the wrists significantly decreases the amplitude of the tremor. Surgeons should consider using wrist supports when performing parts of operations which necessitate a high degree of accuracy. © 2010 Wiley-Liss, Inc.