Figure 1.
Manhattan Plot and QQ Plot of GWAIS.
Panel A depicts the Manhattan plot for the GWAIS (joint test of association and interaction with coffee, 2df, adjusted for sex, age, PC1 and PC2). The novel spike on chromosome 16 corresponds to 12 GRIN2A SNPs that were genotyped. Imputed SNPs achieved P2df<5×10−8 (see Table 4). Additive model is shown here, Dominant and Recessive are in Figure S1. Dominant and Additive models yielded similar results for top hits (see Table 1). Panel B is the QQ plot where the observed P values (red line) are plotted against the expected P values under no association (straight black line). The plots were made first by including all genotyped SNPs (red), then excluding those in the SNCA, HLA and MAPT regions (green) and finally by excluding GRIN2A (blue).
Table 1.
GRIN2A was the most significant signal in GWAIS.
Figure 2.
GWAS in heavy coffee-drinkers.
Panel A depicts GWAS in heavy coffee drinkers with GRIN2A achieving the lowest P values. The P values in stratified GWAS are for genotyped SNP's main effect on PD risk, adjusted for sex, age, PC1 and PC2. Imputed SNPs (not shown here) achieved P = 3×10−8 (see Table 4). Additive model is shown here; see Figure S1 for Dominant model. Dominant and additive models yielded similar results for top hits (see Table 2). Panel B is the QQ plot for heavy coffee drinkers where the observed P values (red line) are plotted against the expected P values under no association (straight black line). The plots were made first by including all SNPs (red), then excluding SNCA, HLA and MAPT (green) and finally by excluding GRIN2A (blue). Unlike the QQ plot for GWAIS, the effects of SNCA, HLA and MAPT are unnoticeable. The only deviation is seen at the extreme <10−5 which is primarily due to GRIN2A.
Figure 3.
GWAS in light coffee-drinkers.
Neither the Manhattan plot (Panel A) nor the QQ plot (Panel B) exhibit evidence of association between GRIN2A and PD among individuals who drink little or no coffee.
Table 2.
GRIN2A was the most significant result in GWAS in heavy coffee-drinkers.
Table 3.
PD risk conditioned on GRIN2A genotype and coffee use.
Table 4.
GWAIS and GWAS results on combined genotyped and imputed data.