GWAS studies of nicotine dependence-related phenotypes have reported associations to markers in GRM7 [39–42]. Examining gene expression levels of GRM7 in the GTEx portal (http://www.gtexportal.org/home/gene/GRM7) showed higher expression in different parts of brain including the cortex, hypothalamus and hippocampus (S7 Fig), which included 84.3% NHW and 13.7% African Americans in their expression analysis. Liu et al.[40] performed a combined analysis of pooled DNA samples from both European and African American subjects in a case-control study of substance dependence, and GRM7 was among the many genes showing some evidence of allele frequency differences between cases and controls. A related gene (GRM8 on chr. 7) was identified in another study of heroin addiction, but the relationship between quantitative measures of smoking behavior and other substance abuse remains tenuous [43]. This is the first study of polymorphic structural variants (CNVs) and quantitative measures of smoking behavior, and the first time any association between polymorphic CNVs on chromosome 3p26.1 has been reported to be associated with relatively heavy smokers among African American subjects.
