Written and verbal language are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits—specifically reading disability (RD) and language impairment (LI)—are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic, and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR=1.81, p=5.45 × 10−7) and COL4A2 (OR=1.71, p=7.59×10−7). Markers within NDST4 showed the strongest associations with LI individually (OR=1.827, p=1.40×10−7). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (p=0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.
Subject motion during brain magnetic resonance spectroscopy (MRS) acquisitions generally reduces the magnetic field (B0) homogeneity across the volume of interest, or voxel. This is the case even if prospective motion correction ensures that the voxel follows the head. We introduce a novel method for rapidly mapping linear variations in B0 across a small volume using two-dimensional excitations. The new field mapping technique was integrated into a prospectively motion-corrected single-voxel 1H MRS sequence. Interference with the MRS measurement was negligible and there was no penalty in scan time. Frequency shifts were also measured continuously, and both frequency and first-order shim corrections were applied in real time. Phantom experiments and in vivo studies demonstrated that the resulting motion- and shim-corrected sequence is able to mitigate line broadening and maintain spectral quality even in the presence of large-amplitude subject motion.
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