Table 2.

Clinical features of mutation carriers vs. mutation-negative index cases

	LRRK2	PRKN	GBA1 a	Mutation-negative b	LRRK2		PRKN		GBA1
	N = 30	N = 26	N = 70	N = 431	Beta (95% CI)	P-value	Beta (95% CI)	P-value	Beta (95% CI)	P-value
Age at onset (mean ± sd)	57.7 (13.4)	28.3 (8.7)	49.1 (14.5)	52.3 (15.0)	3.98 (-0.87, 8.84)	0.108	−13.3 (-18.8, -7.82)	2.50E−06	−2.2 (−5.46, 1.13)	0.197
Motor features (mean ± sd)
MDS-UPDRS Part III	25.2 (14.7)	29.7 (16.5)	27.2 (14.7)	26.5 (17.4)	−0.85 (−7.67, 5.97)	0.806	−4.5 (−13.0, 3.90)	0.290	−0.47 (−5.53, 4.58)	0.855
Motor Severity Score	6.8 (9.9)	1.8 (1.7)	6.2 (5.8)	6.3 (6.7)	0.33 (−2.68, 3.35)	0.829	−4.34 (−7.51, −1.16)	0.008	−0.19 (−2.29, 1.90)	0.856
Motor subtype (%)
Tremor-dominant	18.2	41.2	24.4	39.1
PIGD-dominant	77.3	58.8	65.8	52.1	1.14 (0.00, 2.27)	0.049	−0.46 (−1.67, 0.75)	0.457	0.68 (−0.12, 1.49)	0.096
Intermediate	4.5	0	9.8	8.8	0.03 (−2.22, 2.29)	0.976	NA	NA	0.58 (−0.69, 1.84)	0.371
Hoehn and Yahr stage (%)
0–1.5	43.5	16.7	31.8	38.2
2 or 2.5	30.4	38.9	40.9	37.8	−0.38 (−1.43, 0.66)	0.475	0.06 (−1.57, 1.70)	0.939	−1.79 (−0.62, 0.96)	0.673
3+	26.1	44.4	27.3	24	−0.11 (−1.23, 1.00)	0.843	0.71 (−1.12, 2.55)	0.445	0.17 (−0.77, 1.10)	0.726
Motor complications (%)
Dyskinesias	43.5	35.3	27.5	26	1.06 (0.13, 1.96)	0.022	−0.94 (−2.38, 0.36)	0.175	−0.20 (−1.08, 0.61)	0.646
Motor fluctuations	66.7	56.2	43.6	43.4	1.22 (0.25, 2.28)	0.016	−1.63 (−3.24, −0.15)	0.037	−0.29 (−1.12, 0.50)	0.480
Off dystonia	27.3	35.3	20	24	0.58 (−0.53, 1.57)	0.274	−1.15 (−2.58, 0.14)	0.095	−0.52 (−1.51, 0.35)	0.267
Motor aspects of daily living (mean ± sd)	13.1 (7.8)	9.8 (7.2)	13.7 (8.4)	13.5 (9.2)	−0.12 (−3.24, 3.00)	0.939	−9.1 (−12.7, −5.5)	1.14E−06	−0.49 (−2.69, 1.70)	0.658
Autonomic dysfunction (%)
Orthostatic hypotension	42.9	38.5	46.2	48.6	−0.21 (−1.01, 0.57)	0.607	−0.89 (−1.83, 0.00)	0.056	−0.13 (−0.67, 0.41)	0.642
Constipation	50	34.6	65.2	49.1	−0.05 (−0.83, 0.74)	0.906	−0.82 (−1.83, 0.11)	0.092	0.72 (0.17, 1.29)	0.012
Urinary dysfunction	64.3	48	64.6	64.2	−0.07 (−0.87, 0.78)	0.865	−0.82 (−1.80, 0.12)	0.090	0.03 (−0.53, 0.61)	0.917
REM sleep behaviour disorder (%)	46.4	48	54.7	39.9	0.32 (−0.45, 1.09)	0.412	−0.46 (−1.40, 0.45)	0.323	0.58 (0.02, 1.13)	0.041
Neuropsychiatric symptoms (%)
Apathy	26.1	27.8	27.7	30.7	−0.12 (−1.17, 0.81)	0.813	−0.84 (−2.11, 0.29)	0.165	−0.22 (−0.96, 0.45)	0.528
Depression	4.3	11.1	10.4	14.8	−1.19 (−4.09, 0.43)	0.253	−0.91 (−2.85, 0.53)	0.270	−0.56 (−1.69, 0.37)	0.281
Anxiety	17.4	27.8	16.7	20.8	−0.15 (−1.42, 0.88)	0.796	−0.03 (−1.31, 1.12)	0.958	−0.38 (−1.27, 0.40)	0.368
Dopamine dysregulation syndrome	23.8	16.7	21.3	13.2	0.96 (−0.23, 2.01)	0.088	−0.58 (−2.18, 0.73)	0.417	0.46 (−0.39, 1.25)	0.266
Hallucinations	17.4	11.1	27.1	15.5	0.27 (−1.01, 1.33)	0.637	−1.36 (−3.36, −0.14)	0.112	0.61 (−0.17, 1.33)	0.110
MoCA score (mean ± sd)	26.7 (2.9)	26.6 (2.6)	25.5 (3.1)	26.3 (3.4)	0.53 (−0.85, 1.92)	0.451	0.02 (−1.57, 1.62)	0.976	−0.87 (−1.73, −0.02)	0.045

NA not applicable.

^aExcludes cases not investigated with WGS (n = 3) and GBA1 mutations that coexist with pathogenic mutations in LRRK2 (n = 1), PRKN biallelic (n = 2), PRKN monoallelic (n = 3), PINK1 monoallelic (n = 1) and GCH1 (n = 1). Variants classified as ‘severity unknown’ are included.

^bExcludes mutation-negative cases not investigated with both WGS and MLPA (n = 122), carriers of GBA1 variants and of monoallelic pathogenic PRKN and PINK1 mutations. Mutation carriers vs. mutation-negative PD were compared with linear, logistic or multinomial regression as appropriate, after adjustment for sex, age and disease duration (except age at onset, which was adjusted only for sex and disease duration, and motor severity, which was adjusted only for sex and age). Significance level set at <0.05. MDS-UPDRS items were used to define the following clinical features: dyskinesias (items 4.1 + 4.2 > 0); motor fluctuations (items 4.3 + 4.4 + 4.5 > 0); off-dystonia (item 4.6 > 0); orthostatic hypotension (item 1.12 > 0); constipation (item 1.11 > 0); urinary dysfunction (item 1.10 > 0); apathy (item 1.5 > 0); depression (item 1.3 > 1); anxiety (item 1.4 > 1), impulse control disorder (item 1.6 > 0); hallucinations (item 1.2 > 0 and <4). Motor severity scores are MDS-UPDRD part III scores divided by disease duration in years. Motor subtypes were defined according to Stebbins et al.⁸². Motor aspects of daily living scores are the sum of MDS-UPDRS part II items. REM sleep behaviour disorder was defined as RBDSQ score >5.

Bold font indicates statistical significance (P-value <0.05).