Routine measurement of brain RNA integrity was introduced to supplement the measurement of brain pH that has been undertaken for many years. RIN is tightly correlated to brain pH and is largely affected by events in the agonal period (Barton, Pearson, Najlerahim, & Harrison, 1993; Durrenberger et al., 2010; Monoranu et al., 2009). Brain pH is negatively correlated with the number and severity of hypoxic events in the pre-mortem period (Hardy et al., 1985). Low pH or RNA measurements from brain tissue are a proxy for a more severe agonal period and in the case of AUD, liver cirrhosis and hepatic encephalopathy (D. Sheedy, Say, Stevens, Harper, & Kril, 2012). Their effects on gene expression can exceed the disease itself and are therefore important confounders or covariates in transcriptomic studies (Sutherland, Sheedy, Sheahan, Kaplan, & Kril, 2014).
