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Chunk #33 — 4. ACHIEVING A SYSTEMS-BASED APPROACH TO STUDYING AD — 4.1 The Need for Genomewide Systems-based Studies of AD

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The genetics of alcohol dependence: advancing towards systems-based approaches.
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and the transcriptome of select tissue as a whole, we would obtain effects that are more robust. For instance, recent studies that have examined the covariation between variation in the genome and the transcriptome, and the proteome suggest modest correlations between them (Colantuoni et al., 2011; Ghazalpour et al., 2011). For example, Colantuoni et al’s (2011) examination of how genomewide sequence variation affects gene expression in the prefrontal cortex (PFC) showed that across different racial/ethnic groups, individual SNPs can alter the expression of individual genes in the PFC; furthermore, although the level of gene expression in the PFC varies across the lifespan, it is a consistent set of genes that is expressed. Thus, for future studies, the joint analysis of the genome, transcriptome, and proteome will be essential to understanding the structural and functional changes in our brain and metabolism. A recent example of this approach in alcohol research involved the use of RNA-Seq, ChIP-Seq, and histone H3 lysine 4 trimethylation (H3K4me3) data to identify expression differences in post-mortem hippocampus tissue collected from alcohol and cocaine dependent cases and matching controls (Zhou et al., 2011). Similarly, Schumann et al. (2011) followed up on their GWAS findings that pointed to AUTS2