Table 2. Rare nonsynonymous variants in 22q11.2 deletion-associated early-onset Parkinson’s disease (22q11.2ds-pd) patients compared with 22q11.2 deletion patients with no Parkinson’s disease (22q11.2DS-NPD).

	Rare deleterious coding variant countsa
	22q11.2DS-PD			22q11.2DS-NPD						Analyses
Subject Identifier	PD1	PD2	PD3	NPD1	NPD2	NPD3	NPD4	NPD5	NPD6	PD Mean (SD)	NPD Mean (SD)	pb
Genome-wide total
Loss-of-function variants	9	7	14	22	17	22	13	9	11	10.0 (3.6)	15.7 (5.6)	0.06
Missense variants	97	98	117	102	79	95	90	82	89	104.0 (11.3)	89.5 (8.4)	0.07
Candidate gene-sets for 22q11.2DS-PD
22q11.2 deletion region genes (46 genes)	1c	0	1c	0	0	0	0	0	1c	0.7 (0.6)	0.2 (0.4)	0.14
Known PD candidate genes (43 genesd)	0	0	0e	0	0	0	0	0	0	-	-	-
PD-relevant genes (top 1000 candidate genesf)
Loss-of-function variants	1	1	0	1	0	1	1	3	0	0.7 (0.6)	1.7 (1.1)	0.29
Missense variants	12	7	11	3	4	4	5	8	5	10.0 (2.6)	4.8 (1.7)	0.03

^aRare (MAF<0.01) autosomal heterozygous deleterious variant counts. Only one homozygous variant was identified (missense variant in ZNF418, no apparent functional relevance to PD, in PD3)

^bNominal p value for one-sided independent t-test. Non-parametric Wilcoxon testing yielded the same pattern of results

^cMissense variants in three brain-expressed genes in the proximal typical deletion region, none of which are considered 22q11.2 PD candidate genes [2]: TRMT2A, tRNA methyltransferase 2 homolog A [S. cerevisiae] (PD1); DGCR2, DiGeorge syndrome critical region 2 (PD3); GNB1L, guanine nucleotide binding protein [G protein], beta-polypeptide 1-like (NPD6)

^dPD candidate causative and risk genes (S1 Table)

^eA false positive missense variant in PARK2 (subject PD3) was not confirmed: Sanger sequencing showed no mutation [2].

^fTop 1000 genome-wide genes ranked as potential PD-relevant genes using the genome-wide candidate gene prioritization tool, Endeavour