Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder
DNA methylation may mediate persistent changes in gene function following chronic stress. To examine this hypothesis, we evaluated African American subjects matched by age and sex, and stratified into four groups by post‐traumatic stress disorder (PTSD) diagnosis and history of child abuse. Total Li...
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| Published in | American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 156B; no. 6; pp. 700 - 708 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.09.2011
Wiley-Liss |
| Subjects | |
| Online Access | Get full text |
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| Abstract | DNA methylation may mediate persistent changes in gene function following chronic stress. To examine this hypothesis, we evaluated African American subjects matched by age and sex, and stratified into four groups by post‐traumatic stress disorder (PTSD) diagnosis and history of child abuse. Total Life Stress (TLS) was also assessed in all subjects. We evaluated DNA extracted from peripheral blood using the HumanMethylation27 BeadChip and analyzed both global and site‐specific methylation. Methylation levels were examined for association with PTSD, child abuse history, and TLS using a linear mixed model adjusted for age, sex, and chip effects. Global methylation was increased in subjects with PTSD. CpG sites in five genes (TPR, CLEC9A, APC5, ANXA2, and TLR8) were differentially methylated in subjects with PTSD. Additionally, a CpG site in NPFFR2 was associated with TLS after adjustment for multiple testing. Notably, many of these genes have been previously associated with inflammation. Given these results and reports of immune dysregulation associated with trauma history, we compared plasma cytokine levels in these subjects and found IL4, IL2, and TNFα levels associated with PTSD, child abuse, and TLS. Together, these results suggest that psychosocial stress may alter global and gene‐specific DNA methylation patterns potentially associated with peripheral immune dysregulation. Our results suggest the need for further research on the role of DNA methylation in stress‐related illnesses. © 2011 Wiley‐Liss, Inc. |
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| AbstractList | DNA methylation may mediate persistent changes in gene function following chronic stress. To examine this hypothesis, we evaluated African American subjects matched by age and sex, and stratified into four groups by post-traumatic stress disorder (PTSD) diagnosis and history of child abuse. Total Life Stress (TLS) was also assessed in all subjects. We evaluated DNA extracted from peripheral blood using the HumanMethylation27 BeadChip and analyzed both global and site-specific methylation. Methylation levels were examined for association with PTSD, child abuse history, and TLS using a linear mixed model adjusted for age, sex, and chip effects. Global methylation was increased in subjects with PTSD. CpG sites in five genes (
TPR
,
CLEC9A
,
APC5
,
ANXA2
, and
TLR8
) were differentially methylated in subjects with PTSD. Additionally, a CpG site in
NPFFR2
was associated with TLS after adjustment for multiple testing. Notably, many of these genes have been previously associated with inflammation. Given these results and reports of immune dysregulation associated with trauma history, we compared plasma cytokine levels in these subjects and found IL4, IL2, and TNFα levels associated with PTSD, child abuse, and TLS. Together, these results suggest that psychosocial stress may alter global and gene-specific DNA methylation patterns potentially associated with peripheral immune dysregulation. Our results suggest the need for further research on the role of DNA methylation in stress-related illnesses. DNA methylation may mediate persistent changes in gene function following chronic stress. To examine this hypothesis, we evaluated African American subjects matched by age and sex, and stratified into four groups by post‐traumatic stress disorder (PTSD) diagnosis and history of child abuse. Total Life Stress (TLS) was also assessed in all subjects. We evaluated DNA extracted from peripheral blood using the HumanMethylation27 BeadChip and analyzed both global and site‐specific methylation. Methylation levels were examined for association with PTSD, child abuse history, and TLS using a linear mixed model adjusted for age, sex, and chip effects. Global methylation was increased in subjects with PTSD. CpG sites in five genes ( TPR , CLEC9A , APC5 , ANXA2 , and TLR8 ) were differentially methylated in subjects with PTSD. Additionally, a CpG site in NPFFR2 was associated with TLS after adjustment for multiple testing. Notably, many of these genes have been previously associated with inflammation. Given these results and reports of immune dysregulation associated with trauma history, we compared plasma cytokine levels in these subjects and found IL4, IL2, and TNFα levels associated with PTSD, child abuse, and TLS. Together, these results suggest that psychosocial stress may alter global and gene‐specific DNA methylation patterns potentially associated with peripheral immune dysregulation. Our results suggest the need for further research on the role of DNA methylation in stress‐related illnesses. © 2011 Wiley‐Liss, Inc. DNA methylation may mediate persistent changes in gene function following chronic stress. To examine this hypothesis, we evaluated African American subjects matched by age and sex, and stratified into four groups by post-traumatic stress disorder (PTSD) diagnosis and history of child abuse. Total Life Stress (TLS) was also assessed in all subjects. We evaluated DNA extracted from peripheral blood using the HumanMethylation27 BeadChip and analyzed both global and site-specific methylation. Methylation levels were examined for association with PTSD, child abuse history, and TLS using a linear mixed model adjusted for age, sex, and chip effects. Global methylation was increased in subjects with PTSD. CpG sites in five genes (TPR, CLEC9A, APC5, ANXA2, and TLR8) were differentially methylated in subjects with PTSD. Additionally, a CpG site in NPFFR2 was associated with TLS after adjustment for multiple testing. Notably, many of these genes have been previously associated with inflammation. Given these results and reports of immune dysregulation associated with trauma history, we compared plasma cytokine levels in these subjects and found IL4, IL2, and TNF levels associated with PTSD, child abuse, and TLS. Together, these results suggest that psychosocial stress may alter global and gene-specific DNA methylation patterns potentially associated with peripheral immune dysregulation. Our results suggest the need for further research on the role of DNA methylation in stress-related illnesses. copyright 2011 Wiley-Liss, Inc. DNA methylation may mediate persistent changes in gene function following chronic stress. To examine this hypothesis, we evaluated African American subjects matched by age and sex, and stratified into four groups by post‐traumatic stress disorder (PTSD) diagnosis and history of child abuse. Total Life Stress (TLS) was also assessed in all subjects. We evaluated DNA extracted from peripheral blood using the HumanMethylation27 BeadChip and analyzed both global and site‐specific methylation. Methylation levels were examined for association with PTSD, child abuse history, and TLS using a linear mixed model adjusted for age, sex, and chip effects. Global methylation was increased in subjects with PTSD. CpG sites in five genes (TPR, CLEC9A, APC5, ANXA2, and TLR8) were differentially methylated in subjects with PTSD. Additionally, a CpG site in NPFFR2 was associated with TLS after adjustment for multiple testing. Notably, many of these genes have been previously associated with inflammation. Given these results and reports of immune dysregulation associated with trauma history, we compared plasma cytokine levels in these subjects and found IL4, IL2, and TNFα levels associated with PTSD, child abuse, and TLS. Together, these results suggest that psychosocial stress may alter global and gene‐specific DNA methylation patterns potentially associated with peripheral immune dysregulation. Our results suggest the need for further research on the role of DNA methylation in stress‐related illnesses. © 2011 Wiley‐Liss, Inc. DNA methylation may mediate persistent changes in gene function following chronic stress. To examine this hypothesis, we evaluated African American subjects matched by age and sex, and stratified into four groups by post-traumatic stress disorder (PTSD) diagnosis and history of child abuse. Total Life Stress (TLS) was also assessed in all subjects. We evaluated DNA extracted from peripheral blood using the HumanMethylation27 BeadChip and analyzed both global and site-specific methylation. Methylation levels were examined for association with PTSD, child abuse history, and TLS using a linear mixed model adjusted for age, sex, and chip effects. Global methylation was increased in subjects with PTSD. CpG sites in five genes (TPR, CLEC9A, APC5, ANXA2, and TLR8) were differentially methylated in subjects with PTSD. Additionally, a CpG site in NPFFR2 was associated with TLS after adjustment for multiple testing. Notably, many of these genes have been previously associated with inflammation. Given these results and reports of immune dysregulation associated with trauma history, we compared plasma cytokine levels in these subjects and found IL4, IL2, and TNFα levels associated with PTSD, child abuse, and TLS. Together, these results suggest that psychosocial stress may alter global and gene-specific DNA methylation patterns potentially associated with peripheral immune dysregulation. Our results suggest the need for further research on the role of DNA methylation in stress-related illnesses. DNA methylation may mediate persistent changes in gene function following chronic stress. To examine this hypothesis, we evaluated African American subjects matched by age and sex, and stratified into four groups by post-traumatic stress disorder (PTSD) diagnosis and history of child abuse. Total Life Stress (TLS) was also assessed in all subjects. We evaluated DNA extracted from peripheral blood using the HumanMethylation27 BeadChip and analyzed both global and site-specific methylation. Methylation levels were examined for association with PTSD, child abuse history, and TLS using a linear mixed model adjusted for age, sex, and chip effects. Global methylation was increased in subjects with PTSD. CpG sites in five genes (TPR, CLEC9A, APC5, ANXA2, and TLR8) were differentially methylated in subjects with PTSD. Additionally, a CpG site in NPFFR2 was associated with TLS after adjustment for multiple testing. Notably, many of these genes have been previously associated with inflammation. Given these results and reports of immune dysregulation associated with trauma history, we compared plasma cytokine levels in these subjects and found IL4, IL2, and TNFα levels associated with PTSD, child abuse, and TLS. Together, these results suggest that psychosocial stress may alter global and gene-specific DNA methylation patterns potentially associated with peripheral immune dysregulation. Our results suggest the need for further research on the role of DNA methylation in stress-related illnesses.DNA methylation may mediate persistent changes in gene function following chronic stress. To examine this hypothesis, we evaluated African American subjects matched by age and sex, and stratified into four groups by post-traumatic stress disorder (PTSD) diagnosis and history of child abuse. Total Life Stress (TLS) was also assessed in all subjects. We evaluated DNA extracted from peripheral blood using the HumanMethylation27 BeadChip and analyzed both global and site-specific methylation. Methylation levels were examined for association with PTSD, child abuse history, and TLS using a linear mixed model adjusted for age, sex, and chip effects. Global methylation was increased in subjects with PTSD. CpG sites in five genes (TPR, CLEC9A, APC5, ANXA2, and TLR8) were differentially methylated in subjects with PTSD. Additionally, a CpG site in NPFFR2 was associated with TLS after adjustment for multiple testing. Notably, many of these genes have been previously associated with inflammation. Given these results and reports of immune dysregulation associated with trauma history, we compared plasma cytokine levels in these subjects and found IL4, IL2, and TNFα levels associated with PTSD, child abuse, and TLS. Together, these results suggest that psychosocial stress may alter global and gene-specific DNA methylation patterns potentially associated with peripheral immune dysregulation. Our results suggest the need for further research on the role of DNA methylation in stress-related illnesses. |
| Author | Cubells, Joseph F. Ressler, Kerry J. Tang, Yilang Smith, Alicia K. Mercer, Kristina B. Conneely, Karen N. Bradley, Bekh Gillespie, Charles F. Weiss, Tamara E. Kilaru, Varun |
| AuthorAffiliation | 1 Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 5 Yerkes National Primate Research Center, Atlanta, Georgia 2 Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 4 Atlanta VA Medical Center, Decatur, Georgia 3 Howard Hughes Medical Institute, Maryland |
| AuthorAffiliation_xml | – name: 3 Howard Hughes Medical Institute, Maryland – name: 5 Yerkes National Primate Research Center, Atlanta, Georgia – name: 4 Atlanta VA Medical Center, Decatur, Georgia – name: 2 Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia – name: 1 Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia |
| Author_xml | – sequence: 1 givenname: Alicia K. surname: Smith fullname: Smith, Alicia K. organization: Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia – sequence: 2 givenname: Karen N. surname: Conneely fullname: Conneely, Karen N. organization: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia – sequence: 3 givenname: Varun surname: Kilaru fullname: Kilaru, Varun organization: Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia – sequence: 4 givenname: Kristina B. surname: Mercer fullname: Mercer, Kristina B. organization: Howard Hughes Medical Institute, Maryland – sequence: 5 givenname: Tamara E. surname: Weiss fullname: Weiss, Tamara E. organization: Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia – sequence: 6 givenname: Bekh surname: Bradley fullname: Bradley, Bekh organization: Atlanta VA Medical Center, Decatur, Georgia – sequence: 7 givenname: Yilang surname: Tang fullname: Tang, Yilang organization: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia – sequence: 8 givenname: Charles F. surname: Gillespie fullname: Gillespie, Charles F. organization: Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia – sequence: 9 givenname: Joseph F. surname: Cubells fullname: Cubells, Joseph F. organization: Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia – sequence: 10 givenname: Kerry J. surname: Ressler fullname: Ressler, Kerry J. email: kressle@emory.edu organization: Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24436220$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/21714072$$D View this record in MEDLINE/PubMed |
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| Keywords | NPFFR2 epigenetic Anxiety disorder Cytokine total life stress Posttraumatic stress disorder Stress PTSD Regulation(control) DNA TPR Epigenetics TLR8 Regulation Methylation Immune system APC5 |
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Am J Psychiatr 158(3): 48 2009; 45 2010; 11 2003; 118 2011; 117 2010; 107 1997; 272 1997; 42 2010; 17 2004; 8 2010; 153B 2004; 7 1999; 286 1999; 45 2008; 105 2008; 3 2009; 12 2010; 20 2003; 129 2004; 36 2008; 29 1999; 14 2000; 61 2007; 6 2003; 160 2008; 65 2006; 281 2001; 13 1996; 66 2009; 65 2007; 282 2011 2000; 68 1994; 151 1998 1999; 67 2006; 6 2010; 362 1997; 27 2007; 12 1995; 8 2009; 36 2009; 31 2002; 64 2010; 334 2006; 47 2008; 48 2009; 9 2003; 27 2005; 10 2006; 181 1999; 156 2007; 41 2008; 42 2008; 299 2007; 44 2005; 18 2001; 158 1994; 51 e_1_2_6_51_1 e_1_2_6_53_1 e_1_2_6_32_1 e_1_2_6_30_1 e_1_2_6_19_1 e_1_2_6_13_1 e_1_2_6_36_1 e_1_2_6_59_1 e_1_2_6_11_1 e_1_2_6_34_1 e_1_2_6_17_1 e_1_2_6_55_1 e_1_2_6_15_1 e_1_2_6_38_1 e_1_2_6_57_1 e_1_2_6_62_1 e_1_2_6_43_1 e_1_2_6_20_1 e_1_2_6_41_1 e_1_2_6_60_1 Kessler RC (e_1_2_6_26_1) 2000; 61 e_1_2_6_9_1 e_1_2_6_5_1 e_1_2_6_7_1 e_1_2_6_24_1 e_1_2_6_49_1 e_1_2_6_3_1 e_1_2_6_22_1 e_1_2_6_28_1 e_1_2_6_45_1 e_1_2_6_47_1 e_1_2_6_52_1 e_1_2_6_54_1 e_1_2_6_10_1 e_1_2_6_31_1 e_1_2_6_50_1 Brewin CR (e_1_2_6_14_1) 2000; 68 e_1_2_6_35_1 e_1_2_6_12_1 e_1_2_6_33_1 e_1_2_6_18_1 e_1_2_6_39_1 e_1_2_6_56_1 e_1_2_6_16_1 e_1_2_6_37_1 e_1_2_6_58_1 e_1_2_6_42_1 e_1_2_6_21_1 e_1_2_6_40_1 e_1_2_6_61_1 Bernstein DP (e_1_2_6_8_1) 1998 e_1_2_6_4_1 e_1_2_6_6_1 e_1_2_6_25_1 e_1_2_6_48_1 e_1_2_6_23_1 e_1_2_6_2_1 e_1_2_6_29_1 e_1_2_6_44_1 e_1_2_6_27_1 e_1_2_6_46_1 |
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| Snippet | DNA methylation may mediate persistent changes in gene function following chronic stress. To examine this hypothesis, we evaluated African American subjects... |
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| SubjectTerms | Adult and adolescent clinical studies Adult Survivors of Child Abuse Anxiety disorders. Neuroses APC5 Biological and medical sciences Black or African American Child abuse CpG islands CpG Islands - genetics Cytokines Cytokines - biosynthesis Cytokines - blood Cytokines - immunology DNA DNA methylation DNA Methylation - genetics DNA Methylation - immunology epigenetic Humans Immune system Inflammation Interleukin 2 Interleukin 4 Medical genetics Medical sciences NPFFR2 Peripheral blood Post-traumatic stress disorder Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry PTSD Sex Social interactions Stress Stress Disorders, Post-Traumatic - genetics Stress Disorders, Post-Traumatic - immunology Stress Disorders, Post-Traumatic - metabolism Stress, Psychological - genetics Stress, Psychological - immunology TLR8 total life stress TPR Trauma Tumor necrosis factor |
| Title | Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder |
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