Imaging Genetics Study of Specific Reading Disability: The Role of Semaphorin6d

The current thesis focused on imaging genetics of specific reading disability (SRD), to better understand the biological risk factors that contribute to SRD. Part 1 of the thesis was a systematic review focusing on summarizing the current imaging genetics literature and characterizing effect sizes of these results, revealing significant associations between reading disability risk genes and brain phenotypes. A Fisher’s test revealed promising results for risk genes that had been replicated, including as DCDC2, KIAA0319, FOXP2, SLC2A3, and ROBO1. Part 2 of the thesis specifically examined associations of the novel candidate gene Semaphorin 6d (SEMA6D) on reading-related regions of interest and reading, revealing associations with white matter volume in the left transverse temporal gyrus, which was significantly associated with reading performance measures. Other phenotypes related to SEMA6D SNPs included cortical thickness in the fusiform gyrus and gyrification in the supramarginal gyrus, but these regions were not related to reading in the current sample. It is possible that the transverse temporal gyrus was more related to reading in this sample due to young participants who are still developing reading skills, with greater reliance on auditory processing for reading. Part 3 applied the imaging genetics literature to a clinical case to determine whether risk factors were related to SRD in a family consisting of twins discordant for SRD and an older sibling with reading difficulty. Results indicated that SNPs in the genes ZNF385D, LPHN3, CNTNAP2, FGF18, NOP9, CMIP, MYO18B, and RBFOX2 corresponded with SRD. Furthermore, cortical thickness in reading-related regions of interest was more similar among the siblings with SRD compared to the twins, with specific asymmetry differences in the transverse temporal and superior temporal gyri. The siblings with SRD also demonstrated reduced leftward asymmetry of grey matter volume and cortical surface area in the fusiform gyrus, supramarginal gyrus, and transverse temporal gyrus. Overall, the current thesis summarized and added to the imaging genetics of SRD literature, demonstrated promising effects of a previously unstudied gene, SEMA6D, and used a clinical application to understand factors that may be related to SRD risk within a single family. Future research in this field using integrative imaging genetics methodology to understand and predict risk of SRD can better early identification and intervention to have a valuable clinical impact on children with SRD.