Figure 4. Genetic associations of NAc and AMY cell populations with psychiatric disease and addiction phenotypes.

(A) MAGMA associations of 12 GWAS for each of 24 cell classes profiled in human NAc.

(B) MAGMA-computed, gene-level Z scores, compared to their reported significant PASCAL scores, for “SmkInit” from Liu et al. (2019). Genes are colored if they were statistically significant for pairwise marker tests, for the corresponding NAc cell class, and additionally labeled if that cell class was Bonferroni significant in MAGMA association with the phenotype.

(C) MAGMA associations for each of 16 cell classes profiled in human AMY.

(D) Same as (B) but for “DrnkWk” and colored/labeled by AMY pairwise cell class markers (no MAGMA-gene set analysis result restriction).

For the MAGMA heatmaps: displayed numbers are the effect size (b) for significant associations (controlled for false discovery rate [FDR] < 0.05), on a Z (standard normal) distribution. Bolded numbers are those that additionally satisfy a strict Bonferroni correction threshold of p < 3.89e–5. Heatmap is colored by empirical log10(p value) for each association test.

AD, Alzheimer’s disease; ADHD, attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; BIP, bipolar disorder; MDD, major depressive disorder; PTSD, posttraumatic stress disorder; SCZ, schizophrenia. The suffix for these (e.g., “.PGC2”) reference the specific study (see STAR Methods). For the Liu et al. (2019) phenotypes: “addxn.,” addiction; “AgeSmk,” age of initiation of regular smoking; “CigDay,” number of cigarettes per day; “DrnkWk,” number of drinks per week; “SmkInit,” whether regular smoking was ever reported (binary variable); “SmkCes,” if so, had an individual stopped smoking (binary variable).