(Core C) The purpose of this core is to obtain genotypes for ~5,000 DNA samples derived from rats that are phenotyped by Projects 1, 2, and 3. In addition, we will perform RNA Sequencing (RNASeq) in support of Research Projects 1 and 2. Finally, we use these data to perform genome wide association studies (GWAS) and a number of related analyses. In the prior funding period, Dr. Palmer was the PI of both this core and a research project that developed techniques for genetic analysis. In this renewal application, those two functions have been consolidated into this core. One of the critical technical advances that made this center possible was our development of genotyping- by-sequencing (GBS) for use in rats. Only three SNP genotyping microarrays have ever been developed for use in rats. All three are expensive (>$300 per sample) and none are currently in production. The lack of affordable genotyping platforms was a major impediment to the use of GWAS and related quantitative genetic approaches in rats. In the past funding period, our P50 center has turned the tide by further improving and widely deploying GBS for use in rats. We have continued to refine our GBS techniques, and are now able to obtain ~3.7 million SNPs for less than $50 per sample. Thus, we have increased our output by more than 30-fold while cutting the costs in half. In addition to obtaining genotypes and performing RNASeq, this core will perform genetic analyses, which include GWAS, phenome-wide association analyses (PheWAS), transcriptome wide association analyses (TWAS), heritability estimates, genetic correlations, and a new approach that we call polygenic transcriptomic risk score (PTRS) prediction. All of these analyses are routinely performed in our laboratory and have been the subjects of prior publications that used rats, mice, and humans.
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