Meta-analysis of epigenome-wide association studies of major depressive disorder
Abstract Epigenetic mechanisms have been hypothesized to play a role in the etiology of major depressive disorder (MDD). In this study, we performed a meta-analysis between two case–control MDD cohorts to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-22744-6 |
| _version_ | 1798044392271904768 |
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| author | Qingqin S. Li Randall L. Morrison Gustavo Turecki Wayne C. Drevets |
| author_facet | Qingqin S. Li Randall L. Morrison Gustavo Turecki Wayne C. Drevets |
| author_sort | Qingqin S. Li |
| collection | DOAJ |
| description | Abstract Epigenetic mechanisms have been hypothesized to play a role in the etiology of major depressive disorder (MDD). In this study, we performed a meta-analysis between two case–control MDD cohorts to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs) in MDD. Using samples from two Cohorts (a total of 298 MDD cases and 63 controls with repeated samples, on average ~ 1.8 samples/subject), we performed an EWAS meta-analysis. Multiple cytosine-phosphate-guanine sites annotated to TNNT3 were associated with MDD reaching study-wide significance, including cg08337959 (p = 2.3 × 10–11). Among DMPs with association p values less than 0.0001, pathways from REACTOME such as Ras activation upon Ca2+ influx through the NMDA receptor (p = 0.0001, p-adjusted = 0.05) and long-term potentiation (p = 0.0002, p-adjusted = 0.05) were enriched in this study. A total of 127 DMRs with Sidak-corrected p value < 0.05 were identified from the meta-analysis, including DMRs annotated to TNNT3 (chr11: 1948933 to 1949130 [6 probes], Sidak corrected P value = 4.32 × 10–41), S100A13 (chr1: 153599479 to 153600972 [22 probes], Sidak corrected P value = 5.32 × 10–18), NRXN1 (chr2: 50201413 to 50201505 [4 probes], Sidak corrected P value = 1.19 × 10–11), IL17RA (chr22: 17564750 to 17565149, Sidak corrected P value = 9.31 × 10–8), and NPFFR2 (chr4: 72897565 to 72898212, Sidak corrected P value = 8.19 × 10–7). Using 2 Cohorts of depression case–control samples, we identified DMPs and DMRs associated with MDD. The molecular pathways implicated by these data include mechanisms involved in neuronal synaptic plasticity, calcium signaling, and inflammation, consistent with reports from previous genetic and protein biomarker studies indicating that these mechanisms are involved in the neurobiology of depression. |
| first_indexed | 2024-04-11T23:03:00Z |
| format | Article |
| id | doaj.art-c0f27d942d0a4ef293505e04dd36dd85 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T23:03:00Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c0f27d942d0a4ef293505e04dd36dd852022-12-22T03:58:05ZengNature PortfolioScientific Reports2045-23222022-11-0112111110.1038/s41598-022-22744-6Meta-analysis of epigenome-wide association studies of major depressive disorderQingqin S. Li0Randall L. Morrison1Gustavo Turecki2Wayne C. Drevets3Neuroscience, Janssen Research and Development, LLCNeuroscience, Janssen Research and Development, LLCDouglas Mental Health University Institute, McGill UniversityNeuroscience, Janssen Research and Development, LLCAbstract Epigenetic mechanisms have been hypothesized to play a role in the etiology of major depressive disorder (MDD). In this study, we performed a meta-analysis between two case–control MDD cohorts to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs) in MDD. Using samples from two Cohorts (a total of 298 MDD cases and 63 controls with repeated samples, on average ~ 1.8 samples/subject), we performed an EWAS meta-analysis. Multiple cytosine-phosphate-guanine sites annotated to TNNT3 were associated with MDD reaching study-wide significance, including cg08337959 (p = 2.3 × 10–11). Among DMPs with association p values less than 0.0001, pathways from REACTOME such as Ras activation upon Ca2+ influx through the NMDA receptor (p = 0.0001, p-adjusted = 0.05) and long-term potentiation (p = 0.0002, p-adjusted = 0.05) were enriched in this study. A total of 127 DMRs with Sidak-corrected p value < 0.05 were identified from the meta-analysis, including DMRs annotated to TNNT3 (chr11: 1948933 to 1949130 [6 probes], Sidak corrected P value = 4.32 × 10–41), S100A13 (chr1: 153599479 to 153600972 [22 probes], Sidak corrected P value = 5.32 × 10–18), NRXN1 (chr2: 50201413 to 50201505 [4 probes], Sidak corrected P value = 1.19 × 10–11), IL17RA (chr22: 17564750 to 17565149, Sidak corrected P value = 9.31 × 10–8), and NPFFR2 (chr4: 72897565 to 72898212, Sidak corrected P value = 8.19 × 10–7). Using 2 Cohorts of depression case–control samples, we identified DMPs and DMRs associated with MDD. The molecular pathways implicated by these data include mechanisms involved in neuronal synaptic plasticity, calcium signaling, and inflammation, consistent with reports from previous genetic and protein biomarker studies indicating that these mechanisms are involved in the neurobiology of depression.https://doi.org/10.1038/s41598-022-22744-6 |
| spellingShingle | Qingqin S. Li Randall L. Morrison Gustavo Turecki Wayne C. Drevets Meta-analysis of epigenome-wide association studies of major depressive disorder Scientific Reports |
| title | Meta-analysis of epigenome-wide association studies of major depressive disorder |
| title_full | Meta-analysis of epigenome-wide association studies of major depressive disorder |
| title_fullStr | Meta-analysis of epigenome-wide association studies of major depressive disorder |
| title_full_unstemmed | Meta-analysis of epigenome-wide association studies of major depressive disorder |
| title_short | Meta-analysis of epigenome-wide association studies of major depressive disorder |
| title_sort | meta analysis of epigenome wide association studies of major depressive disorder |
| url | https://doi.org/10.1038/s41598-022-22744-6 |
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