Table 1 Methylome-wide association studies of Anxiety meeting inclusion criteria.
From: A systematic review of methylome-wide associations with anxiety disorders
Study | Study Design / Cohort Type | Sample Sizea | Outcome/ Diagnostic Instrument | Ethnicity/ % Female | Mean age | DNAm Platform | MTC/ Inflation Reported | Covariates / Comorbidities | Main MWAS Findings | Internal Replication | Data Availability |
|---|---|---|---|---|---|---|---|---|---|---|---|
Iurato et al. [51] | Case-Control / Clinical | 165 (89/76) | Panic / SCID I & II | European/ 59% | Cases: 36.0; Controls: 37.0 | Illumina 450k | 5% FDR / Yes | Age, Sex, CTC, Smoking | No significant CpGs in both sexes. In females, cg07308824 in HECA hypermethylated in cases. | Replication of cg07308824 successful in independent sample of females | Iurato: available in GEO at GSE102468 |
Shimada-Sugimoto et al. [55] | Case-Control / Clinical | 96 (48/48) | Panic / MINI | Japanese/ 65% | Cases: 38.1; Controls: 38.2 | Illumina 450k | 5% FDR / Yes | Age, Sex, CTC, Smoking | 40 significant CpGs; Annotated to 42 genes. | Not attempted | Data available from the National Bioscience Database Center |
Ziegler et al. [56] | Case-Control / Clinical | 116 (56/60) | Panic / SCID I | European/ 78% | Cases: 34.0; Controls: 33.3 | Illumina EPIC | Bonferroni / Yes | Age, Smoking, CTC, 3 PCs from control probes | No significant CpGs identified. | Not attempted | No data availability statement. |
Petersen et al. [54] | Case-Control & Meta-Analysis / Clinical | 251 (133/118)b | Panic / SCID I & II or MINI | European & Japanese/ 61% | Cases: 37.8; Controls: 40.0 | Illumina 450k | Bonferroni / No | Age, Sex, CTC, Smoking, random effect of study | 61 significant CpGs; Annotated to 50 genes. | Not attempted | See respective studies |
Emeny et al. 2017 | Cohort / Pop. | 1,522 | GAD symptoms / GAD-7 | European/ 52% | 58.6 | Illumina 450k | Bonferroni / No | Age, Sex, CTC, BMI, Smoking, Alcohol | cg12701571 in ASB1 was hypermethylated | cg12701571 associated with panic symptoms in panic disorder patients | No data availability statement |
Ciuculete et al. [46] | Case-Control / Pop. | 221 (55, 164) | GAD symptoms / DAWBA | European/ 74% | Low symptom: 15.4; High symptom: 15.7 | Illumina 450k | Bonferroni / No | Age, Sex, CTC, BMI, analysis time point, 2 PCS from most variable CpGs | cg16333992 inSTK32B was hypermethylated | cg16333992 replicated in independent sample of adults | No data availability statement |
Guo et al. [49] | Case-Control and Meta-Analysis / Clinical | 460 (158, 302)c | GAD and OCD / SCID I | Han Chinese/ 50% | GAD: 36.9; OCD: 29.3; Controls: 24.5 | Illumina 450k and EPIC | Benjamini-Hochberg / No | Age, Sex, CTC, PCs to explain 95% of variance in linear model | 1,070 significant CpGs in case group of GAD & OCD; Annotated to 473 genes. 397 CpGs differentially methylated between GAD and OCD; Annotated to 166 genes. | Not attempted | No data availability statement |
Wiegand et al. [23] | Case-Control / Pop | 143 (66/77) | SAD and Severity / SCID & LSAS | European/ 66% | Ce: 25.0; CE: 27.0; Se: 23.9; SE: 28.0 | Illumina EPIC | 5% FDR / No | Age, Sex, CTC | 5 significant CpGs in SLC43A2 and 3 CpGs in TNXB | Not attempted | No data availability statement |
Ohi et al. [53] | Case-Control / Clinical and Pop | 143 SAD (66/77); 263 panicd (182/81) | SAD and Panic / SCID I & II | European/ 65% | SAD cases: 25.8; SAD controls: 25.8; Panic cases: 41.1; Panic controls: 41.4 | Illumina 450k and EPIC | pā<ā9āĆā10ā8 / No | Age, Sex, CTC, PCs related to slides | cg18515031 in ANAPC16 hypermethylated in individuals with SAD compared to controls. No CpG sites associated with panic disorder. | Not attempted | Data sets available upon reasonable request. IDAT files available on GEO |
Hettema et al. [50] | Case-Control / Clinical | 1132 (618/514) | Lifetime Anxiety / CIDI | European/ 65% | Cases; 41.9; Controls: 41.2 | MBD-seq | 10% FDR / Yes | Age, Sex, CTC, Smoking, Lab technical variables, 3 PCs for unmeasured variation / Depression | One significant CpG in APC2 in whole blood, 280 in monocytes, 82 in granulocytes. Annotated to 114 genes. No CpGs associated in T-cells or B-cells. | Replicated two CpGs in FZR1 in monocytes. Enrichment of Discovery findings in monocytes, T-cells and B-cells. | Full results available upon request. NESDA and GSMS data available through corresponding institutions |
Kwon et al. [52] | Case-Control / Clinical | 390 (66/207) | Current Anxietye / CIDI | Korean/ 55% | Cases: 43.0; Controls: 40.4 | Targeted Methyl-Seq | Benjamini-Hochberg / No | Age, Sex | 18 significant CpGs; Annotated to 11 genes. | Not attempted | Data available upon reasonable request |
Domschke et al. [47] | Case-Control / Clinical | 673 (378/295) | Current Anxietyf / CIDI | European/ 56% | Cases: 33.2; Controls: 35.2 | Illumina EPIC | Bonferroni / Yes | Age, Sex, 10 control probe PCs, CTC, Smoking / Depression | 148 significant CpGs; Annotated to 145 genes. | Not attempted | Full summary results available upon request |
