Table 3 Statistical results of clinical and omics-based phenotype analysis. Variables that demonstrated non-normality via Shapiro Wilk were log transformed before running one-way ANCOVA (corrected for sex) and post-hoc Tukey’s to assess cluster-specific trends

Age at Onset

0.983, 0.22

2.160, 0.121

1 vs. 2; 0.107, 1 vs. 3; 0.622, 2 vs. 3; 0.569

Age at Death

0.976, 0.042

2.979, 0.055

1 vs. 2; 0.051, 1 vs. 3; 0.988, 2 vs. 3; 0.168

Disease Duration (years)

0.943; 3.5E-04

4.211; 0.018

1 vs. 2; 0.036, 1 vs. 3; 0.092, 2 vs. 3; 0.890

Post-mortem Delay

0.951, 4.4E-04

0.178, 0.837

1 vs. 2; 0.997, 1 vs. 3; 0.851, 2 vs. 3; 0.855

mtDNA Coverage

0.944, 3.2E-04

1.886, 0.157

1 vs. 2; 0.988, 1 vs. 3; 0.145, 2 vs. 3; 0.294

mtDNA Copy Number

0.966; 9.9E-03

1.643, 0.199

1 vs. 2; 0.231, 1 vs. 3; 0.458, 2 vs. 3; 0.945

Telomere Length

0.972, 0.028

2.451, 0.092

1 vs. 2; 0.810, 1 vs. 3; 0.074, 2 vs. 3; 0.350

Biological Age Acceleration

0.971, 0.025

3.858, 0.025

1 vs. 2; 0.110, 1 vs. 3; 0.414, 2 vs. 3; 0.020

RNA Age Acceleration

0.981, 0.142

2.847, 0.063

1 vs. 2; 0.055, 1 vs. 3; 0.973, 2 vs. 3; 0.203

TargetALS (motor cortex)

Phenotype

Normality (Shapiro-Wilk W, p-value)

One-Way ANCOVA (F-statistic, p-value)

Post-Hoc Analysis (Tukey p-value)

Age at Onset

0.977, 7.1E-03

2.463, 0.088

1 vs. 2; 0.075, 1 vs. 3; 0.968, 2 vs. 3; 0.194

Age at Death

0.984, 0.053

4.456, 0.013

1 vs. 2; 0.009, 1 vs. 3; 0.765, 2 vs. 3; 0.089

Diagnostic Delay

0.776, 2.9E-14

0.926, 0.398

1 vs. 2; 0.840, 1 vs. 3; 0.373, 2 vs. 3; 0.867

Disease Duration (years)

0.705, 2.2E-16

2.403, 0.094

1 vs. 2; 0.114, 1 vs. 3; 0.944, 2 vs. 3; 0.110

Post-mortem Delay

0.883, 6.8E-10

1.176, 0.311

1 vs. 2; 0.892, 1 vs. 3; 0.405, 2 vs. 3; 0.349

RNA Age Acceleration

0.989, 0.292

6.004, 3.1E-03

1 vs. 2; 0.002, 1 vs. 3; 0.420, 2 vs. 3; 0.092

Zucca (blood)

Phenotype

Normality (Shapiro-Wilk W, p-value)

One-Way ANCOVA (F-statistic, p-value)

Post-Hoc Analysis (Tukey p-value)

Age at Onset

0.926, 0.242

0.078, 0.926

1 vs. 2; 0.926, 1 vs. 3; 0.987, 2 vs. 3; 0.986

RNA Age Acceleration

0.990, 0.999

0.178, 0.839

1 vs. 2; 0.868, 1 vs. 3; 0.936, 2 vs. 3; 0.992

van Rheenen (blood)

Phenotype

Normality (Shapiro-Wilk W, p-value)

One-Way ANCOVA (F-statistic, p-value)

Post-Hoc Analysis (Tukey p-value)

Age at Onset

0.975, 2.0E-06

2.282, 0.103

1 vs. 2; 0.100, 1 vs. 3; 0.738, 2 vs. 3; 0.634

Disease Duration (years)

0.815; < 2.2E-16

0.00950, 0.991

1 vs. 2; 0.990, 1 vs. 3; 1.000, 2 vs. 3; 0.992

RNA Age Acceleration

0.973, 9.1E-07

2.788, 0.063

1 vs. 2; 0.082, 1 vs. 3; 0.479, 2 vs. 3; 0.787