Table 2.

Characteristics of the interacting variants at SNCA locus.

PD-associated taxa	Interacting SNP at SNCA	Interaction P	Effect allele	Effect allele freq.	a. Association with PD		b. Association with gene expression
					Present study OR (P)	GWAS OR (P)	Gene	eQTL P	Tissue studied	Source
Corynebacterium_1	rs356229_T/C	2E−3	C	0.4	1.3 (0.04)	1.3 (3E−42)	SNCA	1E−13	Whole blood	eQTLGen
							SNCA	9E−5	Esophagus mucosa	GTEx
							SNCA-AS1	2E−7	Pituitary	GTEx
							RP11-115D19.1	3E−14	Skin	GTEx
							MMRN1	5E−5	Spleen	GTEx
							MMRN1	4E−9	Whole Blood	eQTLGen
Porphyromonas	rs10029694_G/C	6E−3	C	0.1	1.1 (0.62)	1.1 (2E−14)	RP11-115D19.1	1E−5	Skin	GTEx
							RP11-115D19.2	7E−6	Skin	GTEx
Prevotella	rs6856813_T/C	0.01	T	0.6	0.9 (0.43)	—	SNCA	3E−49	Whole blood	eQTLGen
							SNCA	2E−5	Artery-Tibial	GTEx
							SNCA	1E−4	Artery-Aorta	GTEx
							MMRN1	3E−11	Whole blood	eQTLGen

Test of statistical interaction nominated three different and independent single nucleotide variants (SNPs) at SNCA region as modifiers of the relative increase of three opportunistic pathogens in PD gut microbiome. (a) Two of the variants were detected in prior GWAS as being directly associated with PD. Association of rs356229_T/C with PD was detected in a GWAS meta-analysis conducted in 2014 with ~19,000 PD cases and ~100,000 controls²³. Association of rs10029694 with PD was detected in a larger GWAS meta-analysis conducted in 2019 with 37,688 PD cases and 1.4 million controls³. (b) All three SNPs are expression quantitative loci (eQTL) for SNCA, lncRNA antisense to SNCA known to regulate SNCA expression (SNCA-AS1, RP11-115D19.1), lncRNA RP11-115D19.2 which is embedded in and antisense to SNCA, and MMRN1, a protein coding gene (mutimerin 1) upstream of 5′ SNCA which is often multiplicated along with SNCA multiplication in familial PD. Data were obtained from eQTL databases GTEx and eQTLGen. Important to note that the names of genera are not standardized across reference databases and caution should be exercised when comparing results from different studies; these genera were defined using SILVA reference database. Effect allele: variant of interacting SNP that is associated with increased differential abundance of the taxon in PD vs. controls. pdgene.org: catalogue of PD-associated genes. RP11-115D19.1 is denoted as AC093866.1 in Fig. 1, RP11-115D19.2 is denoted as AC097478.2 in Fig. 1.