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Table 2 External validation of metabolites previously associated with PD in an untargeted, comprehensive profiling with 226 metabolite features: Shao et al, 2021 [7] reported 50 metabolites which were differential to PD. Of these 34 were also detected and annotated at high confidence to the same metabolite in our population. Results for 20 of the 34 metabolites associated with PD are shown here, including individual study findings and combined results

From: Untargeted serum metabolomics reveals novel metabolite associations and disruptions in amino acid and lipid metabolism in Parkinson’s disease

Metabolite

Shao et al. 2021 Table S4

Current Study

amanida Meta-Analysisa

metaDEA Meta-Analysisb

Validation

p value

Fold change

p value

Fold change

95% CI

Combined FC

Adj combined p-value

Mean FC

SD

pseudo t-score

p-Cresol glucuronide

0.0021

2.15

1E-05

3.80

2.10, 6.90

3.14

7.5E-06

2.86

1.50

3.688

Direction, Significance, & Magnitude

p-Cresol sulfate

0.0278

1.08

8E-05

1.55

1.25, 1.93

1.37

2.3E-04

1.29

1.29

1.426

Direction, Significance, & Magnitude

FFA 20:3

0.0000

0.63

0.000

1.23

1.10, 1.36

0.98

1.8E-06

0.88

1.60

-0.381

Significance

FFA 20:4

0.0004

0.65

0.002

1.18

1.06, 1.31

0.97

1.4E-04

0.88

1.52

-0.445

Significance

Uridine

0.0300

0.91

0.003

1.18

1.06, 1.31

1.08

3.0E-03

1.04

1.20

0.274

Significance

Phenylacetyl-L-glutamine

0.0023

1.57

0.008

1.27

1.06, 1.51

1.36

1.5E-03

1.41

1.16

3.254

Direction, Significance, & Magnitude

FFA 18:2

0.0106

0.73

0.01

1.17

1.04, 1.31

1.00

3.3E-03

0.92

1.40

-0.334

Significance

Trigonelline

0.0119

0.53

0.03

0.73

0.55, 0.97

0.66

9.5E-03

0.62

1.25

-2.966

Direction, Significance, & Magnitude

Ubiquinone 1

0.0030

0.73

0.03

1.16

1.01, 1.34

0.99

3.3E-03

0.92

1.39

-0.359

Significance

FFA 14:1

0.0100

0.77

0.04

1.25

1.01, 1.53

1.06

9.5E-03

0.98

1.41

-0.079

Significance

Kynurenine

0.0113

0.86

0.05

0.93

0.86, 1.00

0.91

1.3E-02

0.89

1.06

-2.855

Direction & Significance

Biliverdin

0.0003

0.7

0.08

0.74

0.52, 1.04

0.73

1.8E-03

0.72

1.04

-11.837

Direction, Significance, & Magnitude

Pantothenic acid

0.0174

0.85

0.09

0.79

0.61, 1.03

0.81

2.2E-02

0.82

1.05

-5.440

Direction, Significance, & Magnitude

FFA 20:2

0.0090

0.76

0.09

1.12

0.98, 1.28

0.98

1.6E-02

0.92

1.32

-0.415

Significance

Indolelactic acid

0.0109

0.81

0.09

0.91

0.82, 1.02

0.88

1.7E-02

0.86

1.09

-2.620

Direction & Significance

FFA 22:5

0.0002

0.63

0.17

1.09

0.97, 1.22

0.91

2.3E-03

0.83

1.47

-0.686

Significance

FFA 19:1

0.0179

0.78

0.18

1.15

0.94, 1.40

1.01

3.3E-02

0.95

1.32

-0.280

Significance

Cortisol

0.0165

1.21

0.19

1.12

0.94, 1.33

1.15

3.3E-02

1.16

1.06

3.932

Direction & Significance

FFA 20:0

0.0307

0.87

0.19

0.88

0.72, 1.07

0.88

5.1E-02

0.87

1.01

-23.371

Direction & Significance

cis-Aconitic acid

0.0078

0.83

0.25

0.90

0.75, 1.08

0.88

2.9E-02

0.86

1.06

-3.602

Direction & Significance

  1. aAmanida: meta-analysis done using amanida R package, designed to combine results when only the fold change, p-value, and sample size are available. For significance evaluation using the statistic result p-value, amanida uses a weighted p-values combination, which is a variant of Fisher’s method. “A gamma distribution is used to assign non-integral weights proportional to study size to each p-value. The logarithmically transformed fold-change values are averaged with weighting by study size.” Amanida reference [23]
  2. bmetaDE: meta-analysis done using metaDEA R package, which averages the study-specific log2FCs and calculates the SD. The "pseudo t-score" is the ratio of mean log2FC to the SD of the log2FCs divided by the square root of the number of comparisons. “This statistic is negative for metabolites with lower abundance and positive for higher abundance and its absolute value will be higher for those metabolites with high and consistent changes across comparisons, and lower for inconsistent and variable fold changes (e.g., upregulated in some datasets and downregulated in others) that are found only in a few comparisons.” metaDEA reference [24]
  3. Significance: individual study p<0.25 and combined p-value<0.05
  4. Direction: individual study fold changes are at least ±5% and directions match between the two studies
  5. Magnitude: Combined log2FC > 0.25 or < -0.25
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Molecular Neurodegeneration

ISSN: 1750-1326