Fig. 5: SPI1 was nominated as candidate gene associated with increased DPW and AUD.

A Locus zoom plot showing DPW, AUD, and mQTL (Fetal brain) associations at 11p.11.2. X-axis represents the positions along chromosome 11 and y-axis represents the −log10 (P) values of each SNP at this locus. P-values for the DPW GWAS (Liu et al, 2019) and AUD GWAS are obtained from aggregated weighted Z statistics. P-values for mQTL meta-analysis were obtained using conventional inverse-variance-weighted meta-analysis. Color of each dot presents the R² for LD at the locus (Red = 0.8–1.0; Orange 0.6–0.79; Green 0.4–0.59; Blue 0.2–0.39 and dark blue <2.0). Yellow line represents the position of rs56030824 identified as a functional variant co-localized with AUD, DPW, and mQTLs in the fetal brain. The tracks show the peaks for promoter marks in 4 major cell types of the brain. Rs56030824 was found to overlap with promoter-specific marks (H3K4me3 and H3K27ac), specifically in microglia. B Effect sizes for DPW GWAS and SPI1 expression in CD14+ monocytes were found to be correlated i.e. decreased alcohol intake was associated with decreased SPI1 expression. Rs56030824 showed the strongest association with DPW and mQTL in the common variant category. The shaded area around trend-line depicts the 95% confidence level intervals plotted using “geom_smooth(method = “lm”)” from ggplot2. C rs56030824 is a strong eQTL and associated with SPI1 expression in CD14+ monocytes. The box in the Box Plot is extending from the 25th percentile to the 75th percentile, with median horizontal line within the box. The whiskers are extending to one and a half times the interquartile range.