DNA Methylation Signatures of Depressive Symptoms in Middle-aged and Elderly Persons Meta-analysis of Multiethnic Epigenome-wide Studies
| العنوان: | DNA Methylation Signatures of Depressive Symptoms in Middle-aged and Elderly Persons Meta-analysis of Multiethnic Epigenome-wide Studies |
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| المؤلفون: | Karl-Heinz Ladwig, Jennifer A. Brody, Thomas H. Mosley, Michelle Luciano, John M. Starr, Zhiying Wang, Guosheng Zhang, Ivana Nedeljkovic, Kathryn L. Evans, André G. Uitterlinden, Chunyu Liu, Tom C. Russ, Eric A. Whitsel, Daniel Levy, Xiuqing Guo, Katri Räikkönen, David J. Porteous, Riccardo E. Marioni, Rozenn N. Lemaitre, Allan F. McRae, Rahul Gondalia, Yun Li, O. Jovanova, Myriam Fornage, Nona Sotoodehnia, Jayandra J. Himali, Jari Lahti, Sudha Seshadri, Johan G. Eriksson, Derek Spieler, Hongsheng Wu, Michael M. Mendelson, Najaf Amin, Melanie Waldenberger, Naomi R. Wray, Amanda J. Drake, Lifang Hou, Jan Bressler, Sonja Kunze, Andrew M. McIntosh, James A. Stewart, Brigitte Kühnel, Annette Peters, Andrea A. Baccarelli, Henning Tiemeier, Ian J. Deary, Joyce B. J. van Meurs, Brenton R. Swenson, Rosie M. Walker |
| المساهمون: | Epidemiology, Internal Medicine, Child and Adolescent Psychiatry / Psychology |
| المصدر: | JAMA Psychiatry JAMA psychiatry 75, 949-959 (2018) Story Jovanova, O, Nedeljkovic, I, Spieler, D, Walker, R M, Liu, C, Luciano, M, Bressler, J, Brody, J, Drake, A J, Evans, K L, Gondalia, R, Kunze, S, Kuhnel, B, Lahti, J, Lemaitre, R N, Marioni, R E, Swenson, B, Himali, J J, Wu, H, Li, Y, McRae, A F, Russ, T C, Stewart, J, Wang, Z, Zhang, G, Ladwig, K-H, Uitterlinden, A G, Guo, X, Peters, A, Räikkönen, K, Starr, J M, Waldenberger, M, Wray, N R, Whitsel, E A, Sotoodehnia, N, Seshadri, S, Porteous, D J, Van Meurs, J, Mosley, T H, McIntosh, A M, Mendelson, M M, Levy, D, Hou, L, Eriksson, J G, Fornage, M, Deary, I J, Baccarelli, A, Tiemeier, H & Amin, N 2018, ' DNA Methylation Signatures of Depressive Symptoms in Middle-aged and Elderly Persons : Meta-analysis of Multiethnic Epigenome-wide Studies ', JAMA Psychiatry, vol. 75, no. 9, pp. 949-959 . https://doi.org/10.1001/jamapsychiatry.2018.1725Test JAMA Psychiatry, 75(9), 949-959. American Medical Association |
| بيانات النشر: | American Medical Association, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, medicine.medical_specialty, Population, Epigenesis, Genetic, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, medicine, Humans, Epigenetics, education, Depression (differential diagnoses), Aged, education.field_of_study, business.industry, Depression, Correction, Epigenome, DNA Methylation, Middle Aged, 3. Good health, Psychiatry and Mental health, 030104 developmental biology, Meta-analysis, Cohort, DNA methylation, Gene-Environment Interaction, business, 030217 neurology & neurosurgery, Genome-Wide Association Study |
| الوصف: | Importance: Depressive disorders arise from a combination of genetic and environmental risk factors. Epigenetic disruption provides a plausible mechanism through which gene-environment interactions lead to depression. Large-scale, epigenome-wide studies on depression are missing, hampering the identification of potentially modifiable biomarkers.Objective: To identify epigenetic mechanisms underlying depression in middle-aged and elderly persons, using DNA methylation in blood.Design, Setting, and Participants: To date, the first cross-ethnic meta-analysis of epigenome-wide association studies (EWAS) within the framework of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium was conducted. The discovery EWAS included 7948 individuals of European origin from 9 population-based cohorts. Participants who were assessed for both depressive symptoms and whole-blood DNA methylation were included in the study. Results of EWAS were pooled using sample-size weighted meta-analysis. Replication of the top epigenetic sites was performed in 3308 individuals of African American and European origin from 2 population-based cohorts.Main Outcomes and Measures: Whole-blood DNA methylation levels were assayed with Illumina-Infinium Human Methylation 450K BeadChip and depressive symptoms were assessed by questionnaire.Results: The discovery cohorts consisted of 7948 individuals (4104 [51.6%] women) with a mean (SD) age of 65.4 (5.8) years. The replication cohort consisted of 3308 individuals (2456 [74.2%] women) with a mean (SD) age of 60.3 (6.4) years. The EWAS identified methylation of 3 CpG sites to be significantly associated with increased depressive symptoms: cg04987734 (P = 1.57 × 10−08; n = 11 256; CDC42BPB gene), cg12325605 (P = 5.24 × 10−09; n = 11 256; ARHGEF3 gene), and an intergenic CpG site cg14023999 (P = 5.99 × 10−08; n = 11 256; chromosome = 15q26.1). The predicted expression of the CDC42BPB gene in the brain (basal ganglia) (effect, 0.14; P = 2.7 × 10−03) and of ARHGEF3 in fibroblasts (effect, −0.48; P = 9.8 × 10−04) was associated with major depression.Conclusions and Relevance: This study identifies 3 methylated sites associated with depressive symptoms. All 3 findings point toward axon guidance as the common disrupted pathway in depression. The findings provide new insights into the molecular mechanisms underlying the complex pathophysiology of depression. Further research is warranted to determine the utility of these findings as biomarkers of depression and evaluate any potential role in the pathophysiology of depression and their downstream clinical effects. |
| وصف الملف: | application/pdf |
| تدمد: | 2168-6238 2168-622X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b4b2f3d1755d5538675f9b49cce09b0aTest https://pure.eur.nl/en/publications/87a878ea-14e6-4a87-8dd7-9c6394988f68Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b4b2f3d1755d5538675f9b49cce09b0a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21686238 2168622X |
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