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Chunk #20 — Results — DNMT3B SNP associations with DNAm and RNAexp

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Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence.
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Using a genome-wide meQTL study of 166 fetal brain samples,36 we found that rs910083-C associates with higher DNAm levels of the probe cg13636640, located 252 base pairs upstream of the DNMT3B gene (β=0.082, P=2.3×10−26). This probe was the only one observed in the region with significant mQTL variants (Supplementary Figure 4). There were a total of 140 SNPs associated with DNAm of this probe (smallest P=1.8×10−45), and we observed associations of these SNPs with nicotine dependence with meta-analysis p-values ranging from 3.66×10−8 for rs910083 to 0.0051 (Supplementary Table 4). To our knowledge, there are no similar data to assess cis-meQTL effects in brain tissues from adults with no psychiatric disease. However, we assessed the cis-acting effect of rs910083 on RNAexp across several adult brain tissues using two independent datasets, GTEx37 followed by Brain eQTL Almanac.38