Table 2 Summary of the characteristics of the 20 studies included in the review
First author and year | Country/ethnicity | Subjects (total n) | Sex (total n) | Age/age groups | Biologic matrix | Analytical platform | Statistics | Quality score |
|---|---|---|---|---|---|---|---|---|
Andraos S. 2021 [64] | Australia | 1166 1324 | 565 M 601 F 174 M 1150 F | 11.4 ± 0.5 11.5 ± 0.5 46.2 ± 6.4 43.6 ± 4.8 years (mean ± SD) | Plasma | UHPLC–MS/MS | Linear mixed-effects models Pearson’s correlation | 8 |
Caterino M. 2020 [35] | Italy | 291 | 152 M 139 F | (1–36 months) 1–6 months 7–12 months 13–24 months 25–36 months | Urine | GC–MS | Dunn’s test Kruskal–Wallis test Mann–Whitney U test | 7 |
Caterino M. 2021 [36] | Italy | 311 | 174 M 137 F | 48–72 h | DBS | LC–MS/MS | Spearman’s correlation PLS-DA VIP | 8 |
Chekmeneva E. 2018 [65] | USA | 132 | N. F. | 40–59 years | Urine | 1H NMR DI-nESI-HRMS UPLC–HRMS | PCA OPLS-DA | 10 |
De Paepe E. 2018 [66] | Belgium | 10 | 5 M 5 F | 25–41 years | Plasma Urine | UHPLC–MS/MS | CV-ANOVA PCA OPLS-DA | 7 |
Dunn W. B. 2014 [38] | UK | 1200 | N. F. | (19–81 years)  < 40 years 40–49 years 50–64 years  > 64 years | Serum | UPLC–MS (+) UPLC–MS (−) GC–MS | ANOVA Kruskal–Wallis test Mann–Whitney U test PLS-DA Random Forests | 10 |
Fan S. 2018 [67] | USA | 120 | 60 M 60 F | N. F. | Urine | GC–MS | Mann–Whitney U test PLS-DA PCA | 6 |
Jovè M. 2016 [68] | Spain | 146 | 68 M 78 F | 30–100 years | Plasma | LC–MS/MS (+) LC–MS/MS (−) | ANOVA PCA Student’s t-test | 7 |
Lau C.-H. E. 2018 [54] | UK France Spain Lithuania Norway Greece | (1192) 199 157 207 201 229 199 | (54.6% M 45.4% F) | 6–11 years | Serum Urine | 1H NMR FIA-MS/MS LC–MS/MS | MWAS with multiple linear regression PCA Pearson’s correlation | 8 |
Lawton K. A. 2008 [55] | Caucasian African-American Hispanic | (269) 61 135 73 | (131 M, 138 F) 20M, 41 F 69 M, 66 F 42 M, 31 F | (20–65 years) 20–35 years 36–50 years 51–65 years | Plasma | LC–MS (+) LC–MS (−) GC–MS | ANCOVA ANOVA | 9 |
Mittelstrass K. 2011 [24] | Germany | 3080 377 | 1452 M, 1552 F 197 M, 180 F | 32–81 years 55–79 years | Serum | LC–MS/MS | PLS Linear regression Partial correlation analysis | 7 |
Rist M. J. 2017 [56] | Germany | 200 | 99 M 101 F | 36–80 years | Plasma Urine | 1H NMR FIA-MS/MS GC(xGC)-MS HILIC-MS/MS UHPLC–MS/MS | Glmnet PLS SVM | 8 |
Ruoppolo M. 2014 [15] | Italy | 76 | 35 M 41 F | 20–45 years | Serum | HPLC LC–MS/MS | SAM Pearson’s correlation Spearman’s correlation | 6 |
Ruoppolo M. 2015 [57] | Italy | 3680 | 1856 M 1824 F | 48–72 h | DBS | LC–MS/MS | Mann–Whitney U test Linear regression PCA | 8 |
Saito K. 2016 [58] | Japan | 60 | 15 M 15 F 15 M 15 F | 25–35 years 25–35 years 55–64 years 55–65 years | Serum | GC–MS HILIC–MS (−) UHPLC–MS (+) UHPLC–MS (−) | Welch’s two-factor t-tests PCA | 9 |
Scalabre A. 2017 [59] | France | 90 | 66 M 24 F | (< 4 mo)  < 1 mo 1 months 2 months 3 months | Urine | 1H NMR | PCA O-PLS CV-ANOVA SRV | 7 |
Slupsky C. M. 2007 [60] | Canada | 60 | 30 M 30 F | 16–69 years | Urine | 1H NMR | ANOVA Mann–Whitney U test PCA PLS-DA | 6 |
Thévenot E. A. 2015 [61] | France | 183 | 100 M 83 F | 40.9 ± 10.3 years (mean ± SD) | Urine | UHPLC–MS(/MS) | Mann–Whitney U test O-PLS Spearman’s correlation | 7 |
Trabado S. 2017 [62] | France | 800 | 417 M 383 F | 18–86 years 37.6 ± 17.2 (mean ± SD) | Plasma | FIA-MS/MS LC–MS/MS | CV-ANOVA OPLS-DA PCA | 8 |
Vignoli A. 2018 [63] | Italy | 844 | 661 M 183 F | 41.0 ± 12.0 years (median ± SD) | Plasma | 1H NMR | PLS-DA Wilcoxon rank-sum test | 6 |