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Chunk #39 — Discussion

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Differential sensitivity of human neurons carrying μ opioid receptor (MOR) N40D variants in response to ethanol.
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The approach of using human iN cells to investigate the synaptic impact of acute and chronic ethanol application on human neurons with a major functional OPRM1 SNP is novel for two reasons: 1) Human studies aimed at understanding the correlation of MOR N40D and an AUD suggest that the G allele confers genetic vulnerability to alcohol dependence (Anton et al., 2008; Bart et al., 2005; Chamorro et al., 2012; Hendershot, Claus, & Ramchandani, 2016; Oslin et al., 2003; Ray & Hutchison, 2004, 2007). However, some clinical studies have not discovered an association between the A118G SNP and alcohol dependence (Arias, Feinn, & Kranzler, 2006; Bergen et al., 1997; Gelernter et al., 2007; Ooteman et al., 2009; Rouvinen-Lagerström et al., 2013; Tidey et al., 2008). Comparisons made between individuals who carry the MOR N40D SNP, which comes from different ethnic backgrounds, can potentially influence the phenotype. Our study employs isogenic stem cell lines, which allows us to specifically study the impact of MOR N40D, without known contributions from any differences in the genetic background or those that can be attributed to