Epigenome-Wide Association of PTSD from Heterogeneous Cohorts with a Common Multi-Site Analysis Pipeline

Details

• Personal Author:
  Aiello AE ; Amstadter AB ; Ashley-Koch AE ; Baker DG ; Beckham JC ; Boks MP ; Bromet E ; Dennis M ; Garrett ME ; Geuze E ; Guffanti G ; Hauser MA ; Kilaru V ; Kimbrel NA ; Koenen KC ; Kuan P-F ; Logue MW ; Luft BJ ; Maihofer AX ; Miller MW ; Mitchell C ; Nievergelt CM ; Nugent NR ; Ratanatharathorn A ; Ressler KJ ; Rutten BPF ; Smith, Adam K. ; Stein MB ; Uddin M ; Vermetten E ; Vinkers CH ; Youssef NA
• Corporate Authors:
  Psychiatric Genomics Consortium Posttramautic Stress Disorder. Epigenetics Workgroup ; VA Mid-Atlantic MIRECC Workgroup
• Description:
  Compelling evidence suggests that epigenetic mechanisms such as DNA methylation play a role in stress regulation and in the etiologic basis of stress related disorders such as Post traumatic Stress Disorder (PTSD). Here we describe the purpose and methods of an international consortium that was developed to study the role of epigenetics in PTSD. Inspired by the approach used in the Psychiatric Genomics Consortium, we brought together investigators representing seven cohorts with a collective sample size of N = 1147 that included detailed information on trauma exposure, PTSD symptoms, and genome-wide DNA methylation data. The objective of this consortium is to increase the analytical sample size by pooling data and combining expertise so that DNA methylation patterns associated with PTSD can be identified. Several quality control and analytical pipelines were evaluated for their control of genomic inflation and technical artifacts with a joint analysis procedure established to derive comparable data over the cohorts for meta-analysis. We propose methods to deal with ancestry population stratification and type I error inflation and discuss the advantages and disadvantages of applying robust error estimates. To evaluate our pipeline, we report results from an epigenome-wide association study (EWAS) of age, which is a well-characterized phenotype with known epigenetic associations. Overall, while EWAS are highly complex and subject to similar challenges as genome-wide association studies (GWAS), we demonstrate that an epigenetic meta-analysis with a relatively modest sample size can be wellpowered to identify epigenetic associations. Our pipeline can be used as a framework for consortium efforts for EWAS. [Description provided by NIOSH]
• Subjects:
  Genetics Occupational Health Quality Control Safety Stress Disorders, Post-Traumatic
• Keywords:
  Analytical Processes Cell Alteration Cell Type Cellular Effects Cellular Function Data Processing Deoxyribonucleic Acids DNA Etiology Gene Regulation Genotype Post-traumatic Stress Disorder PTSD Quality Control Stress Stress Analysis Traumatic Incident Stress

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• ISSN:
  1552-4841
• Document Type:
  Text
• Funding:
  Cooperative Agreement ; Contract
• Genre:
  Journal Article
• Place as Subject:
  California ; Georgia ; Illinois ; Massachusetts ; Michigan ; New York ; North Carolina ; OSHA Region 1 ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 5 ; OSHA Region 9 ; Rhode Island ; Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  174
• Issue:
  6
• NIOSHTIC Number:
  nn:20050693
• Citation:
  Am J Med Genet B Neuropsychiatr Genet 2017 Sep; 174(6):619-630
• Contact Point Address:
  Alicia K. Smith, PhD, Department of Gynecology and Obstetrics, Emory University School of Medicine, 101 Woodruff Circle NE, Ste 4217, Atlanta, GA 30322
• Email:
  alicia.smith@emory.edu
• Federal Fiscal Year:
  2017
• Performing Organization:
  State University New York Stony Brook
• Peer Reviewed:
  True
• Start Date:
  20140701
• Source Full Name:
  American Journal of Medical Genetics Part B Neuropsychiatric Genetics
• End Date:
  20170930
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:472bf48a4160957f72b9a5ab304299ac77c582e20293b31f10f5c9d4c713acd1b64ff4e70369b46265c56ef71ad9cbf8d7aa154b7897a25f5196188790a274ba
• Download URL:
  https://stacks.cdc.gov/view/cdc/210936/cdc_210936_DS1.pdf
• File Type:
  [PDF - 772.43 KB ]