A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients
Epigenetic dysregulation is implicated in the pathogenesis of lupus. We performed a longitudinal analysis to assess changes in DNA methylation in lupus neutrophils over 4 years of follow-up and across disease activity levels using 229 patient samples. We demonstrate that DNA methylation profiles in...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical investigation
2020-11-01
|
| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.143654 |
| _version_ | 1818599982008107008 |
|---|---|
| author | Patrick Coit Lourdes Ortiz-Fernandez Emily E. Lewis W. Joseph McCune Kathleen Maksimowicz-McKinnon Amr H. Sawalha |
| author_facet | Patrick Coit Lourdes Ortiz-Fernandez Emily E. Lewis W. Joseph McCune Kathleen Maksimowicz-McKinnon Amr H. Sawalha |
| author_sort | Patrick Coit |
| collection | DOAJ |
| description | Epigenetic dysregulation is implicated in the pathogenesis of lupus. We performed a longitudinal analysis to assess changes in DNA methylation in lupus neutrophils over 4 years of follow-up and across disease activity levels using 229 patient samples. We demonstrate that DNA methylation profiles in lupus are partly determined by ancestry-associated genetic variations and are highly stable over time. DNA methylation levels in 2 CpG sites correlated significantly with changes in lupus disease activity. Progressive demethylation in SNX18 was observed with increasing disease activity in African American patients. Importantly, demethylation of a CpG site located within GALNT18 was associated with the development of active lupus nephritis. Differentially methylated genes between African American and European American lupus patients include type I IFN–response genes such as IRF7 and IFI44, and genes related to the NF-κB pathway. TREML4, which plays a vital role in TLR signaling, was hypomethylated in African American patients and demonstrated a strong cis–methylation quantitative trait loci (cis-meQTL) effect among 8855 cis-meQTL associations identified in our study. |
| first_indexed | 2024-12-16T12:28:14Z |
| format | Article |
| id | doaj.art-9bde268ed6c2483eb816f978eb9ea2a9 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-12-16T12:28:14Z |
| publishDate | 2020-11-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-9bde268ed6c2483eb816f978eb9ea2a92022-12-21T22:31:47ZengAmerican Society for Clinical investigationJCI Insight2379-37082020-11-01522A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patientsPatrick CoitLourdes Ortiz-FernandezEmily E. LewisW. Joseph McCuneKathleen Maksimowicz-McKinnonAmr H. SawalhaEpigenetic dysregulation is implicated in the pathogenesis of lupus. We performed a longitudinal analysis to assess changes in DNA methylation in lupus neutrophils over 4 years of follow-up and across disease activity levels using 229 patient samples. We demonstrate that DNA methylation profiles in lupus are partly determined by ancestry-associated genetic variations and are highly stable over time. DNA methylation levels in 2 CpG sites correlated significantly with changes in lupus disease activity. Progressive demethylation in SNX18 was observed with increasing disease activity in African American patients. Importantly, demethylation of a CpG site located within GALNT18 was associated with the development of active lupus nephritis. Differentially methylated genes between African American and European American lupus patients include type I IFN–response genes such as IRF7 and IFI44, and genes related to the NF-κB pathway. TREML4, which plays a vital role in TLR signaling, was hypomethylated in African American patients and demonstrated a strong cis–methylation quantitative trait loci (cis-meQTL) effect among 8855 cis-meQTL associations identified in our study.https://doi.org/10.1172/jci.insight.143654Autoimmunity |
| spellingShingle | Patrick Coit Lourdes Ortiz-Fernandez Emily E. Lewis W. Joseph McCune Kathleen Maksimowicz-McKinnon Amr H. Sawalha A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients JCI Insight Autoimmunity |
| title | A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients |
| title_full | A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients |
| title_fullStr | A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients |
| title_full_unstemmed | A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients |
| title_short | A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients |
| title_sort | longitudinal and transancestral analysis of dna methylation patterns and disease activity in lupus patients |
| topic | Autoimmunity |
| url | https://doi.org/10.1172/jci.insight.143654 |
| work_keys_str_mv | AT patrickcoit alongitudinalandtransancestralanalysisofdnamethylationpatternsanddiseaseactivityinlupuspatients AT lourdesortizfernandez alongitudinalandtransancestralanalysisofdnamethylationpatternsanddiseaseactivityinlupuspatients AT emilyelewis alongitudinalandtransancestralanalysisofdnamethylationpatternsanddiseaseactivityinlupuspatients AT wjosephmccune alongitudinalandtransancestralanalysisofdnamethylationpatternsanddiseaseactivityinlupuspatients AT kathleenmaksimowiczmckinnon alongitudinalandtransancestralanalysisofdnamethylationpatternsanddiseaseactivityinlupuspatients AT amrhsawalha alongitudinalandtransancestralanalysisofdnamethylationpatternsanddiseaseactivityinlupuspatients AT patrickcoit longitudinalandtransancestralanalysisofdnamethylationpatternsanddiseaseactivityinlupuspatients AT lourdesortizfernandez longitudinalandtransancestralanalysisofdnamethylationpatternsanddiseaseactivityinlupuspatients AT emilyelewis longitudinalandtransancestralanalysisofdnamethylationpatternsanddiseaseactivityinlupuspatients AT wjosephmccune longitudinalandtransancestralanalysisofdnamethylationpatternsanddiseaseactivityinlupuspatients AT kathleenmaksimowiczmckinnon longitudinalandtransancestralanalysisofdnamethylationpatternsanddiseaseactivityinlupuspatients AT amrhsawalha longitudinalandtransancestralanalysisofdnamethylationpatternsanddiseaseactivityinlupuspatients |