We included age, sex, ethnicity, brain weight, brain pH, PMI, tissue hemisphere, cause of death, blood toxicology, smoking status, neuropathology and liver pathology as covariates in analysis. Neuropathology and brain weight were both significantly associated with expression level in the NAc; no covariates were associated with expression level in the PFC (Supplementary Table S7). We detected no difference in expression level between AD cases and controls in either NAc (p=0.75) or PFC (p=0.23) (Figure 6A,B and Supplementary Table S7A,B). After controlling for covariates, expression of LOC339975 is significantly reduced in carriers of the associated non-reference allele in NAc (p=0.003, Figure 6C, Supplementary Table S7C) but did not differ by genotype in PFC (p=0.54, Figure 6D, Supplementary Table S7D). Alternative regulation in NAc and PFC is consistent with the presence of several distinct transcription factor binding sites upstream of lncRNA genes (Alam et al., 2014). Although we do not detect case/control differences in expression, our data suggest the associated allele of rs11726136 has functional consequence based on the reduced LOC339975 expression observed in the NAc in heterozygotes.
