Table 2 Blood-based genome-wide meQTL studies (sample size > 100) in whole blood or blood-derived cell samples
From: Genetic impacts on DNA methylation: research findings and future perspectives
Ref. | Sample sizea | Methylation assay | Genotyping assay | Significant CpGsb | Significance thresholdc | Remarks |
|---|---|---|---|---|---|---|
[50] | 27,750 | Illumina 450K | 1000Gd | cis (≤ 1 Mbp), 43.5% trans (> 1 Mbp), 4.5% | pcis<1×10−8,ptrans<1×10−14 | Study design: two-phase meta-analysis in a total of 36 cohorts. Additional analysis: replication of 188,017 meQTLs in external sample (76% for cis and 79% for trans). |
[35] | 4170 | Illumina 450K | Affymetrix 500K and 50K MIP, 1000Gd | cis (≤ 1 Mbp), 29.3% trans (> 1 Mbp), 3.3% | FWER1 < 5% (pcis<2×10−11,ptrans<1.5×10−14) | Additional analysis: replication of effect direction in two external samples (81–99%). |
[136] | 429 | Illumina 450K | GOLDN studye | cis (≤ 1 Mbp), 0.3% | FWER1 < 5% (p<5.6×10−10) | Study design: response meQTL, with log transformed post-/pre-treatment methylation values. |
[38] | 1111 | Illumina EPIC | Illumina CoreExome, 1000Gd | trans, 12.2% | FWER1 < 5% (p<6.5×10−14) | Effect size: mean methylation change per additional reference allele of 3.46% (s=3.01%). |
[60] | 156 [monocytes] (two samples) | Illumina EPIC | Illumina Omni, WGS, 1000Gd | cis (≤ 100 kbp), 12.6% | FDR3 < 5% (p<1×10−5) | Study design: separate meQTLs discovery for the two samples, joint results reported. Additional analysis: trans association restricted to SNPs in TFs genes vicinity. |
[53] | 1980 (two samples) | Illumina 450K | Illumina 610-Quad | cis (≤ 2 Mbp), 15.4–15.7% trans (> 2 Mbp), 0.5–0.6% | FWER1 < 5% (pcis<1×10−11,ptrans<1×10−13) | Study design: separate meQTLs discovery for the two samples. Additional analysis: replication of CpGs in both samples (13.3% for cis and 0.5% for trans). |
[93] | 337 | Illumina 450K | Illumina CytoSNP, 1000Gd | cis (≤ 500 kbp), 18.3% | FDR3 < 1% |  |
[157] | 729 | Illumina 450K | Illumina Exome, Hap300 and Omni, 1000Gd | cis (≤ 500 kbp), 12.1% | FWER1 < 5% (p<9.4×10−11) | Additional analysis: variance meQTLs. |
[85] | 460 [cord blood and whole blood] (two samples) | Illumina 450K | Illumina Omni, 1000Gd | cis (≤ 0.5–1 Mbp), 8.1–19.2% | FDR3 < 5% | Study design: separate meQTLs discovery for two samples with different parameters. Additional analysis: meQTLs co-localization with results from two published studies. |
[51] | 3,841 | Illumina 450K | CODAM34, LLD9, LLS38, NTR12, and RS studiese, GoNLd | cis (≤ 250 kbp), 34.4% | FDR3 < 5% (p<1.4×10−4) | Additional analysis: trans association restricted to 6111 informative SNPs. |
[65] | 744 [T cells and whole blood] (two samples) | MCC-seq, WGBS | WGS, Illumina Omni, inferred from WGBS, 1000Gd | cis (≤ 250 kbp), 16.0–18.1% | FDR4 < 10% | Study design: separate meQTLs discovery for the two samples. Additional analysis: meQTL in visceral adipose tissue samples, ASM analyses and genotype-independent tests, and validation on Illumina 450K. |
[78] | 525 [neutrophils, monocytes and T cells] (three samples) | Illumina 450K | WGS | cis (≤ 500 kbp), 9.9% | FWER1 < 5% | Study design: separate meQTLs discovery for the three samples, mean results reported. |
[37] | 3948 [cord blood and whole blood] (five samples) | Illumina 450K | Illumina Hap550 and 660W, 1000Gd | cis (≤ 1 Mbp), 6.1–8.0% trans(>1 Mbp), 0.5–0.7% | FWER1 < 0.2% (p<1×10−14) | Study design: separate meQTLs discovery for the five samples. Additional analysis: replication of CpGs in pairwise comparisons (83–98% for cis and 88–98% for trans). |
[54] | 850 | Illumina450K | Illumina Hap550, Exon510, 1M and 1M-Duo | cis (≤ 50 kbp), 13.8% | FWER1 < 5% (p<2.6×10−9) |  |
[55] | 1748 [lymphocytes] (cancer-case and control samples) | Illumina 450K | OFCCRe, Affymetrix 500K | cis (≤ 1 Mbp), 13.9% trans(> 1 Mbp), 0.5% | FDR4 < 5% (pcis<4.8×10−10,ptrans<3.2×10−13) | Study design: joint meQTLs discovery for the two samples; trans analysis excluded CpG sites with cis meQTLs. Additional analysis: replication of meQTL-CpG pairs in two external samples (83.6% for trans). |
[52] | 697 | MBD-seq | Affymetrix SNP 5.0 and 6.0, Illumina Omni, 1000Gd | cis (≤ 1 Mbp), 15% trans(> 1 Mbp), 0.1% | FDR4 < 1% | Additional analysis: replication of findings in one sample of schizophrenia cases (π1= 95% for cis, 98.7% for trans same chromosome, and 99.3% for trans different chromosome). |
[86] | 264 [cord blood and whole blood] (three samples) | Illumina 27K | Illumina Omni, Affymetrix SNP 5.0 and 6.0, HapMapd | cis (≤50 kbp), 0.7–1.5% | FWER2 <5% | Study design: separate meQTLs discovery for the three samples. Additional analysis: replication of meQTL-CpG pairs in pairwise comparisons (17.8–69.5%); meQTL in four brain regions samples. |
[59] | 177 [T cells and LCL] | Illumina 450K | Illumina Omni, 1000Gd | cis (≤ 5 kbp), 5.4–7.8% | FDR3 < 10% | Study design: separate meQTLs discovery for the two samples. Additional analysis: meQTL in fibroblasts sample. |
[32] | 171 | Illumina 27K | Illumina Hap300, 610-Quad, 1M-Duo and 1.2M-Duo, HapMapd | cis (≤ 50), 6.3% | FDR3 < 5% (p<1×10−5) |  |