Chunk #15 — Results — Total CHRNA5 mRNA level in frontal cortex is strongly associated with variants located upstream of the gene in individuals of both African and European ancestry
The insertion-deletion variant rs3841324 within the putative promoter region of CHRNA5 is highly correlated with rs880395 and rs588765 (r2>0.8; Figure S1a) in our brain samples of European ancestry, however it is very weakly correlated with rs880395 (r2 = 0.12) and rs588765 (r2 = 0.16) in brain samples of African ancestry (Figure S1b). rs588765 has a modest correlation with rs880395 in samples of African ancestry (r2 = 0.63; Figure S1b). To test whether the associations of CHRNA5 mRNA expression with rs3841324 and with rs588765 are due to the LD with rs880395, we performed conditional analyses. When the effect of rs880395 on CHRNA5 mRNA expression was included as a covariate, the association between rs3841324 or rs588765 and CHRNA5 expression level was no longer significant in samples of African ancestry or in samples of European ancestry. Conversely, in conditional analysis controlling for the effect of rs3841324, the association of rs880395 with CHRNA5 mRNA expression remains statistically significant in samples of African ancestry (p = 1.79×10−5) and in samples of European ancestry (p = 1.99×10−3). Similarly, conditional analysis showed rs880395 remains significantly associated with
