Table 1. GRIN2A was the most significant signal in GWAIS.

								Dominant					Additive
					MAF	MAF	HWE	SNP		Interaction		2df	SNP		Interaction		2df
CHR	Gene	SNP	BP	Minor/Major Allele	Case	Control	P	OR (SE)	P	OR (SE)	P	P	OR (SE)	P	OR (SE)	P	P
Novel PD-association identified via interaction with coffee
16	GRIN2A	rs4998386	9978046	T/C	0.08	0.12	0.54	0.82 (0.12)	0.17	0.49 (0.11)	2×10−3	1×10−6	0.84 (0.11)	0.19	0.50 (0.11)	1×10−3	1×10−6
16	GRIN2A	rs17569693	9987686	G/A	0.08	0.12	0.54	0.79 (0.11)	0.10	0.51 (0.12)	4×10−3	1×10−6	0.80 (0.10)	0.09	0.54 (0.12)	5×10−3	2×10−6
16	GRIN2A	rs8043728	10003004	T/C	0.09	0.12	0.88	0.82 (0.12)	0.16	0.53 (0.12)	5×10−3	8×10−6	0.82 (0.11)	0.13	0.57 (0.12)	0.01	8×10−6
16	GRIN2A	rs8056683	10052710	T/C	0.09	0.13	1.00	0.82 (0.12)	0.17	0.52 (0.12)	3×10−3	4×10−6	0.83 (0.11)	0.14	0.55 (0.11)	4×10−3	4×10−6
16	GRIN2A	rs9927926	10057405	C/T	0.09	0.13	1.00	0.82 (0.12)	0.17	0.52 (0.12)	3×10−3	4×10−6	0.83 (0.11)	0.14	0.55 (0.11)	4×10−3	4×10−6
16	GRIN2A	rs17671033	10068727	A/G	0.09	0.13	1.00	0.85 (0.12)	0.24	0.50 (0.11)	2×10−3	3×10−6	0.85 (0.11)	0.20	0.53 (0.11)	2×10−3	4×10−6
16	GRIN2A	rs9933111	10072100	G/A	0.09	0.13	0.88	0.85 (0.12)	0.24	0.49 (0.11)	2×10−3	2×10−6	0.85 (0.11)	0.20	0.53 (0.11)	2×10−3	2×10−6
16	GRIN2A	rs13331465	10077968	T/C	0.09	0.13	0.88	0.85 (0.12)	0.23	0.49 (0.11)	2×10−3	2×10−6	0.85 (0.11)	0.19	0.53 (0.11)	2×10−3	2×10−6
16	GRIN2A	rs13336632	10078155	C/A	0.09	0.13	0.88	0.85 (0.12)	0.23	0.49 (0.11)	2×10−3	2×10−6	0.85 (0.11)	0.19	0.52 (0.11)	2×10−3	2×10−6
16	GRIN2A	rs1448270	10082819	T/G	0.09	0.13	0.77	0.86 (0.12)	0.29	0.49 (0.11)	2×10−3	5×10−6	0.86 (0.11)	0.24	0.53 (0.11)	2×10−3	5×10−6
16	GRIN2A	rs11866570	10113676	C/T	0.11	0.15	0.18	0.89 (0.12)	0.35	0.51 (0.11)	1×10−3	8×10−6	0.92 (0.11)	0.46	0.54 (0.11)	2×10−3	3×10−5
16	GRIN2A	rs1448253	10128367	C/T	0.09	0.13	0.67	0.83 (0.11)	0.18	0.52 (0.12)	3×10−3	4×10−6	0.84 (0.11)	0.18	0.55 (0.11)	3×10−3	5×10−6
Well-established PD-associated genes identified via their main effect
4	SNCA	rs356220	90860363	T/C	0.43	0.35	0.77	1.37 (0.16)	0.01	1.25 (0.23)	0.23	3×10−5	1.36 (0.11)	2×10−4	1.05 (0.14)	0.69	3×10−6
4	SNCA	rs356168	90893454	G/A	0.51	0.44	0.89	1.33 (0.17)	0.03	1.33 (0.26)	0.16	1×10−4	1.28 (0.10)	3×10−3	1.09 (0.14)	0.51	5×10−5
17	MAPT	rs199533	42184098	T/C	0.17	0.22	0.15	0.65 (0.08)	2×10−4	1.10 (0.21)	0.63	7×10−5	0.68 (0.07)	2×10−4	1.10 (0.18)	0.57	7×10−5
6	HLA	rs3129882	32517508	G/A	0.46	0.40	0.78	1.25 (0.15)	0.07	1.26 (0.24)	0.22	2×10−3	1.24 (0.10)	0.01	1.08 (0.14)	0.54	5×10−4

Also see Figure 1. GWAIS analysis was [SNP+SNP*coffee] test with 2 df adjusting for sex, age, PC1 and PC2. The test examines the significance of the SNP main effect and its interaction with coffee, without introducing the significant effect of coffee on PD. Results for GRIN2A were equally significant under Dominant and Additive models. Recessive model had no clear signal (see Figure S1). Also shown are the results obtained with the same dataset and under the same analytic model for the known PD genes SNCA, MAPT and HLA. SNCA and HLA had reached P<5×10⁻⁸ in our GWAS. The fall in significance in GWAIS is due in part to 1/3 reduction in sample size due to unavailability of coffee data, and also the penalty imposed by the added degree of freedom. GRIN2A did not have a strong main effect to be noticed in GWAS, but in GWAIS, the inclusion of coffee and interaction placed GRIN2A higher than SNCA, HLA and MAPT.