Table 1.

Select Values for five factors entered into the P_REDIGT score formula

Factor E: Exposome
Type of modifier (or surrogate)	Nature of risk modifier (if known)	Assigned value	Select ref(s) used to create value
Association with elevated risk
Neurotoxin	i.v. MPTP exposure (each event)	1	Langston et al., Science 1983
	i.v. Mn2+ exposure (each event)	0.5	Stepens et al., NEJM 2008
	Pesticide exposure (cumulative)	0.25	Bellou et al., Parkins Rel Dis 2016
	Farm life before age 20 years	0.25	Bellou et al., Parkins Rel Dis 2016
Head trauma	Concussive events (cumulative)	1	Mez et al., Alz Res Therap 2015
	(Sub)concussive events (cumulative)	0.5	Mez et al., Alz Res Therap 2015
Xenobiotic exposure	Encephalitis (select pathogens)	2	Jang et al., Biochim Biophys Acta 2008
	Chronic infection (e.g. H. pylori)	1	Bu et al., Park Rel Dis 2015
Chronic constipation	Lasting for ≥ 20 years	1	Ross et al., Park Rel Dis 2012
	Lasting for 10–19 years	0.5	Ross et al., Park Rel Dis 2012
	Lasting for 5–9 years	0.25	Ross et al., Park Rel Dis 2012
Reduced olfaction	Anosmia (UPSIT score ≤ 28/40)	1	Muirhead et al., The Otolaryngol 2013
	Hyposmia (UPSIT score 29–33/40)	0.5	Muirhead et al., The Otolaryngol 2013
No known association with risk modulator	Little cumulative pathogen exposure
	Age of proband
	≤ 50 years	0
	51–59 years	0.005
	60–69 years	0.0075
	70–79 years	0.02
	≥ 80 years	0.03
Association with lower risk
Smoking history	Current smoker for ≥ 20 years	−0.75	Ritz et al., Arch Neurol 2007
	Current smoker for 11–19 years	−0.5	Ritz et al., Arch Neurol 2007
	Past smoker for ≥ 20 years	−0.25	Ritz et al., Arch Neurol 2007
	Past smoker for 11–19 years	−0.125	Ritz et al., Arch Neurol 2007
	Any smoking history ≤ 10 years	−0.0625	Ritz et al., Arch Neurol 2007
Caffeine intake	≥ 2 cups/day (recent)	−0.25	Palacios et al., Mov Dis 2012
	≥ 1 cup/day (recent)	−0.125	Palacios et al., Mov Dis 2012
Physical exercise	Regular for ≥ 20 years	−0.25	Bellou et al., Parkins Rel Dis 2016
	Irregular for ≥ 20 years	−0.125	Bellou et al., Parkins Rel Dis 2016
	Regular for ≤ 19 years	−0.125	Bellou et al., Parkins Rel Dis 2016

Factor D: DNA (Genetics)
Gene (locus)/Family history	Type of genetic variant	Assigned value	Select ref(s) used to create value
Association with elevated risk
SNCA	Gene triplication (n = 4 alleles)	1	Trinh et al., JAMA Neurol 2014
	Gene duplication (n = 3 alleles)	0.75	Trinh et al., JAMA Neurol 2014
	Mutation (e.g. p.A53T; p.A30P)	0.75	Trinh et al., JAMA Neurol 2014
	Rep1 repeat expansion (5′)	0.5	Markopoulou et al., Parkins Rel Dis 2014
	Other risk variants as per GWAS	0.25	Nalls et al., Lancet Neurol 2014
PARKIN or DJ‐1 or PINK1	Point mutation (het)	1	Kitada et al., Nature 1998
	Copy number variant (het)	1	Pankratz et al., PLOS One 2011
	Exon deletion (het)	1	Kitada et al., Nature 1998
GBA	Point mutation (het; homo)	0.5	Alcalay et al., JAMA Neurol 2014
LRRK2	Point mutation (het; homo)	0.5	Trinh et al., JAMA Neurol 2014
Other risk loci identified by GWAS	Single‐nucleotide polym. (SNPs)	0.1–0.25	Nalls et al., Lancet Neurol 2015
Family history of disease
No known family history	Overall low genetic risk	0.01	Elbaz et al., Neurology 2003
Positive family history	1st degree relative with bona fide PD	0.5	Sveinbjoernsdottir et al., NEJM 2000
Positive family history	2nd degree relative with bona fidePD	0.25	Sveinbjoernsdottir et al., NEJM 2000
Positive family history	3rd degree relative with bona fide PD	0.125	Sveinbjoernsdottir et al., NEJM 2000
Association with lower risk
LRRK2	Bona fide protective SNPs	−0.5	Ross et al., Lancet Neurol 2011

Factor I: Initiation of tissue response
Type of pathophysiological effect	Outcome(s) of effect in cells/tissue	Assigned value	Select ref(s) used to create value
Pathophysiological response
α‐synuclein dysregulation	Accumulation (n = 4 SNCA alleles)	1	Kuo et al., Hum Mol Gen 2010
	Accumulation (e.g. p.A53T; p.A30P)	0.5	Kuo et al., Hum Mol Gen 2010
	Accumulation (n = 3 SNCA alleles)	0.5	Kuo et al., Hum Mol Gen 2010
	Accumulation (Rep1 repeat expansion)	0.25	Cronin et al., Hum Mol Gen 2009
	Accumulation (GBA1 mutation)	0.25	Cullen et al., Ann Neurol 2011
	Accumulation (select LRRK2 mutant)	0.25	Zimprich et al., Neuron 2004
Tau dysregulation	Accumulation (MAPT mutation)	1	Kumar et al., J Biol Chem 2014
	Accumulation (encephalitis)	0.5	Jang et al., Biochim Biophys 2008
	Accumulation (select LRRK2 mutation)	0.25	Zimprich et al., Neuron 2004
	Accumulation (concussive traumas)	0.5	Mez et al., Alz Res Therap 2015
	Accumulation (subconcuss. traumas)	0.25	Mez et al., Alz Res Therap 2015
Parkin deficiency	Redox change; mitoch. dysfunction	1	Palacino et al., J Biol Chem 2004
DJ‐1 deficiency	Redox change; mitoch. dysfunction	1	Rousseaux et al., PNAS 2012
Pink1 deficiency	Redox change; mitoch. dysfunction	1	Glasl et al., Exp Neurol 2012
Neurotoxicant (e.g. MPTP)	Mitochondria degeneration; ROS rise	1	Fornai et al, PNAS 2005
Chronic inflammation	Cytokine/immune cell dysregulation	0.25	Dzamko et al., Mov Dis 2016
Presence of anxiety/depression	Surrogate of disease process in CNS	0.25	Bellou et al., Parkins Rel Dis 2016
Presence of REM sleep disorder	Surrogate of disease process in CNS	0.25	Postuma et al., Sleep Med 2016
Paucity of pathophysiological response	Adjusting for age:
	≤ 50 years	0
	51–59 years	0.001
	60–69 years	0.002
	70–79 years	0.003
	≥ 80 years	0.004

Factor G: Sex (Gender)	Sex	Assigned value	Select ref(s) used to create value
General population
LRRK2 wild‐type	Male	1.2	Berg et al., Mov Dis 2015
	Female	0.8	Berg et al., Mov Dis 2015
Genotyped subjects
Bona fide LRRK2 mutation carrier	Male	0.8	Marder et al., Neurology 2015
	Female	1.2	Marder et al., Neurology 2015

Factor T: Time
Measurement of time	Years lived	Assigned value	Select ref(s) used to create value
Capturing ageing, latency, progression	Subject's actual age	1–100	Driver et al., Neurology 2009