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Chunk #8 — GENE EXPRESSION IN CULTURED CELLS

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5. Collaborative Study on the Genetics of Alcoholism: Functional genomics.
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To dissect genetic risk‐associated differences in gene expression from those caused by exposure to ethanol, McClintick et al. 10 examined the effects of 24 h ethanol exposure (75 mM) on lymphoblastoid cell lines (LCLs). A paired design (each cell served as its own control in comparing ± ethanol) allowed detection of small differences between cells generated from COGA participants, 21 with and 21 without AUD. 99% of the genes detectably expressed in these LCLs are also expressed in brain. Differences between participants with and without AUD included 13 genes previously identified as associated with AUD or related traits, including KCNA3, DICER1, ZNF415, CAT, SLC9A9, and PPARGC1B. The ethanol exposure altered expression of 51% of the unique genes expressed in these cells, but the differences were modest. Genes affected included ANK3, EPHB1, SLC1A1, SLC9A9, NRD1, and SH3BP5, which were reported to be associated with AUD or related phenotypes in two GWAS. 17 , 18