Project 6 Project VI of the Florida LDRC, titled Imaging genetics in SRD: Mega- and meta-analyses, is designed in response to the RFA-HD-17-006's stipulation to obtain converging evidence through the utilization of multiple methodologies?neuroimaging and genetic in the case of Project VI?in order to both discover and highlight the most robust and replicable facets of the genome-brain connection in Specific Reading Disabilities (SRD). Project VI is contextualized by the overall premise of the P50 to reflect on the status of science in the field of learning disabilities (LD) in general and SRD in particular and, therefore, is framed to generate such a reflection in the subfield of imaging genetics of SRD. With that in mind, we propose a set of imaging-genetic meta-analytic studies. Specifically, we are proposing to establish a merged data set that combines behavior, neuroimaging, and genetic (GWAS) data generated by a group of USA and European investigators.
Specific Aim 1 (SA1) of Project VI is committed to the construction of such a database; it establishes the procedures for data merging, quality control, deposition, and manipulation. At the time of submission, we have a firm commitment from contributing investigators to generate a dataset of 1,202 individuals. We have secured three more tentative commitments that have the potential to substantially increase the dataset. Moreover, we have a set of additional investigators who have expressed interest, but with whom we have not yet followed up to appraise the general compatibility of both the brain and genetic data (i.e., the recruitment, collection, and analyses parameters). SA2 is a continuation and extension of the activities of Project VI over two previous cycles of funding.
This aim will provide an opportunity to interrogate the genetic findings assembled in Project VI so far for their robustness, replicability, and generalizability using these merged data. Thus, SA2 assures the continuity of the work carried out by Project VI throughout the two generations of the Florida LDRC. In contrast, SA3 is exploratory and innovative, both to the field of SRD and to Project VI. It proposes a reversed GWAS (or set of GWASes) that capitalizes on the availability of multiple neuroimaging phenotypes in the large merged dataset that we will assemble in SA1. Importantly, to maintain the spirit and the scope of the proposed work, we will utilize behavioral data only for the purpose of grouping or controlling for level of performance in SA2 and SA3. In summary, this iteration of Project VI corresponds to the general theme of the third-generation Florida LDRC: it capitalizes on its own trajectory developed throughout the two previous cycles of funding, proposes a set of mega- and meta-analytic studies, and creates an opportunity to utilize and further develop a curated communal resource that has the potential to become a platform for reproducibility tests in the field of SRD.
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