Figure 1
Flow chart presenting the selection of the studies included in the current review.
Table 1
Gene, chromosome position, possible mechanisms of function, total number of studies (with comparison between ET cases and Controls), number of studies with association, number of studies without association and sample characteristics for the most examined genes for association with ET (Data from GWASs not included).
| Gene | Chromosome position*1 | Possible Mechanisms | Number of studies | Studies with association | Studies without association | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total | With association | Without association | In Caucasians/North Americans | In Asians | Total Cases | Total Controls | In Caucasians/North Americans | In Asians | Total Cases | Total Controls | |||
| LINGO1 | Chromosome 15: 77,613,027–77,820,900 | neurite outgrowth, axonal regeneration, regulation of the myelination and neuronal survival | 11 | 7 | 4 | 5 | 2 | 2,751 | 3,073 | 2 | 2 | 711 | 2,186 |
| DRD3 | Chromosome 3: 114,128,652–114,199,407 | dopamine receptor | 8 | 3 | 5 | 3 | 0 | 507 | 516 | 4 | 1 | 919 | 1,266 |
| SLC1A2 | Chromosome 11: 35,251,205–35,420,063 | regulates glutamate at synaptic cleft and extracellularly | 5 | 2 | 3 | 0 | 2 | 630 | 2,204 | 2 | 1 | 749 | 1,657 |
| LRRK2 | Chromosome 12: 40,196,744–40,369,285 | elevated LRRK2 kinase activity leads to neuronal toxicity | 5 | 1 | 4 | 0 | 1*2 | 450 | 827 | 1 | 3 | 1,165 | 3,650 |
| FUS/TLS | Chromosome 16: 31,180,110–31,194,871 | ALS and FTD pathways | 5*3 | 1 | 4 | 0 | 1 | 513 | 6,169 | 3 | 1 | 729 | 1,251 |
| SNCA | Chromosome 4: 89,724,099–89,838,315 | PD pathways | 3 | 1 | 2 | 1 | 0 | 46 | 100 | 2 | 0 | 767 | 1,406 |
| MAPT | Chromosome 17: 45,894,382–46,028,334 | PD pathways | 3 | 1 | 2 | 1 | 0 | 356 | 409 | 2 | 0 | 449 | 528 |
| HMOX1 | Chromosome 22: 35,380,361–35,394,207 | heme catabolism, lead toxicity | 3 | 1 | 2 | 1 | 0 | 202 | 747 | 1 | 1 | 427 | 447 |
| HMOX2 | Chromosome 16: 4,474,690–4,510,347 | heme catabolism, lead toxicity | 3 | 2 | 1*4 | 2 | 0 | 404 | 965 | 0 | 1 | 225 | 229 |
ET, essential tremor; LINGO1, leucine-rich repeat and lg domain containing nogo receptor-interacting protein 1; SLC1A2, solute carrier family 1 member 2; LRRK2, leucine-rich repeat kinase-2; FUS/TLS, Fused in Sarcoma/Translocated in Liposarcoma; DRD3, dopamine D3 receptor; SNCA, a-synuclein; MAPT, microtubule associated protein tau; HMOX1, Heme Oxygenase 1; HMOX2, Heme Oxygenase 2; ALS, amyotrophic lateral sclerosis; FTD, frontotemporal dementia; PD, Parkinson’s disease; GWASs, genome-wide association studies.
*1 Based on https://www.ensembl.org/index.html.
*2 90% Asians.
*3 Rajput et al. (2014) and Merner et al. (2012) are not included.
*4 The interaction of ALAD rs1800435 with the HMOX2 rs1051308 could be weakly associated with the familial ET.
Table 2
Results from meta-analyses of the LINGO1 rs9652490, LINGO1 rs11856808, SLC1A2 rs3794087, STK32B rs10937625and PPARGC1A rs17590046 for association with ET.
| Gene | Polymorphism | Number of studiesRef. | Population | Heterogeneity | Meta-analysis model | Test for overall effect | ||
|---|---|---|---|---|---|---|---|---|
| I2 | PQ | OR (95% CI) | P-value | |||||
| LINGO1 | rs9652490 | 10 [283133343537383940] | Mixed | 58% | 0.01 | Random | 1.12 (0.97–1.30) | 0.11 |
| LINGO1 | rs11856808 | 7 [313435383940] | Mixed | 53% | 0.05 | Random | 1.06 (0.91–1.24) | 0.43 |
| SLC1A2 | rs3794087 | 6 [5051525354] | Mixed | 67% | 0.01 | Random | 0.95 (0.77–1.16) | 0.60 |
| STK32B | rs10937625 | 2 [5556] | Asian | 61% | 0.11 | Fixed | 0.80 (0.65–0.99) | 0.04 |
| PPARGC1A | rs17590046 | 2 [5556] | Asian | 59% | 0.12 | Fixed | 0.79 (0.61–1.03) | 0.09 |
[i] ET, essential tremor; LINGO1, leucine-rich repeat and lg domain containing nogo receptor-interacting protein 1; SLC1A2, solute carrier family 1 member 2; PPARGC1A, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha; RIT2, Ras like without CAAX 2; STK32B, serine/threonine kinase 32B; OR, odds ratio; CI, confidence interval.
Figure 2
Forest Plots presenting the results from meta-analyses.
Table 3
Results from the sensitivity meta-analyses of the LINGO1 rs9652490 for association with ET.
| Omitted study | Heterogeneity | Meta-analysismodel | Test for overall effect | ||
|---|---|---|---|---|---|
| I2 | PQ | OR (95% CI) | P-value | ||
| Clark et al., (2010) [31] | 58% | 0.01 | Random | 1.10 (0.94–1.29) | 0.22 |
| Thier et al., German (2010) [40] | 33% | 0.15 | Fixed | 1.04 (0.95–1.14) | 0.43 |
| Thier et al., French (2010) [40] | 56% | 0.02 | Random | 1.10 (0.95–1.26) | 0.21 |
| Villarino-Guell et al., 2 (2010) [28] | 52% | 0.04 | Random | 1.16 (0.99–1.36) | 0.06 |
| Zuo et al., (2010) [35] | 62% | 0.007 | Random | 1.14 (0.97–1.33) | 0.10 |
| Tan et al., (2010) [33] | 59% | 0.01 | Random | 1.11 (0.94–1.30) | 0.21 |
| Lorenzo-Betancor et al., (2011) [34] | 57% | 0.02 | Random | 1.16 (0.99–1.35) | 0.06 |
| Wu et al., (2011) [37] | 62% | 0.008 | Random | 1.14 (0.98–1.33) | 0.10 |
| Bourasa et al., (2011) [39] | 62% | 0.007 | Random | 1.14 (0.97–1.34) | 0.11 |
| Radovica et al., (2011) [38] | 62% | 0.007 | Random | 1.13 (0.97–1.33) | 0.11 |
[i] ET, essential tremor; LINGO1, leucine-rich repeat and lg domain containing nogo receptor-interacting protein 1; OR, odds ratio; CI, confidence interval.