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Author Notes:

Correspondence: Shareefa Dalvie, s.dalvie1@uct.ac.za

This work would not have been possible without the contributions of the investigators who comprise the PGC-PTSD working group, and especially the more than 206,000 research participants worldwide who shared their life experiences and biological samples with PGC-PTSD investigators. Full acknowledgements for each study are in the Supplementary Note.

Disclosures: H.R.K. is a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative (ACTIVE), which in the last 3 years was supported by AbbVie, Alkermes, Amygdala Neurosciences, Arbor, Ethypharm, Indivior, Lilly, Lundbeck, Otsuka, and Pfizer.

H.R.K. and J.G. are named as inventors on PCT patent application #15/878,640 entitled: “Genotype-guided dosing of opioid agonists,” filed January 24, 2018.

In the past 3 years, D.J.S. has received research grants and/or consultancy honoraria from Lundbeck and Sun.

In the past 3 years, R.C.K. received support for his epidemiological studies from Sanofi Aventis; was a consultant for Johnson & Johnson Wellness and Prevention, Sage Pharmaceuticals, Shire, Takeda; and served on an advisory board for the Johnson & Johnson. Services Inc. Lake Nona Life Project.

Kessler is a co-owner of DataStat, Inc., a market research firm that carries out healthcare research. M.B.S. has in the past 3 years been a consultant for Aptinyx, Bionomics, Dart Neuroscience, Janssen, Jazz Pharmaceuticals, Neurocrine Biosciences, Oxeia Biopharmaceuticals, and Pfizer.

R.Y. is a co-inventor of the following patent application: “Genes associated with posttraumatic-stress disorder. European Patent# EP 2334816 B1.

Subjects:

Research Funding:

This work was funded by Cohen Veterans Bioscience, the NIMH/U.S. Army Medical Research and Materiel Command Grant R01MH106595 to C.M.N., I.L., K.J.R. and K.C.K., One Mind, and supported by 5U01MH109539 to the Psychiatric Genomics Consortium. Statistical Analysis were carried out on the NL Genetic Cluster computer (URL) hosted by SURFsara.

Genotyping of samples was supported in part through the Stanley Center for Psychiatric Genetics at the Broad Institute of MIT and Harvard.

This research has been conducted using the UK biobank resource under application number 16577.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Psychiatry
  • Gene environment correlation
  • Adult depression
  • Major depression
  • Wide association
  • Adversity
  • Metaanalysis
  • Disorder
  • Trauma
  • Health
  • Experiences

Genomic influences on self-reported childhood maltreatment

Journal Title:

Translational Psychiatry

Volume:

Volume 10, Number 1

Publisher:

, Pages 38-38

Type of Work:

Article | Final Publisher PDF

Abstract:

Childhood maltreatment is highly prevalent and serves as a risk factor for mental and physical disorders. Self-reported childhood maltreatment appears heritable, but the specific genetic influences on this phenotype are largely unknown. The aims of this study were to (1) identify genetic variation associated with self-reported childhood maltreatment, (2) estimate SNP-based heritability (h2snp), (3) assess predictive value of polygenic risk scores (PRS) for childhood maltreatment, and (4) quantify genetic overlap of childhood maltreatment with mental and physical health-related phenotypes, and condition the top hits from our analyses when such overlap is present. Genome-wide association analysis for childhood maltreatment was undertaken, using a discovery sample from the UK Biobank (UKBB) (n = 124,000) and a replication sample from the Psychiatric Genomics Consortium-posttraumatic stress disorder group (PGC-PTSD) (n = 26,290). h2snp for childhood maltreatment and genetic correlations with mental/physical health traits were calculated using linkage disequilibrium score regression. PRS was calculated using PRSice and mtCOJO was used to perform conditional analysis. Two genome-wide significant loci associated with childhood maltreatment (rs142346759, p = 4.35 × 10−8, FOXP1; rs10262462, p = 3.24 × 10−8, FOXP2) were identified in the discovery dataset but were not replicated in PGC-PTSD. h2snp for childhood maltreatment was ~6% and the PRS derived from the UKBB was significantly predictive of childhood maltreatment in PGC-PTSD (r2 = 0.0025; p = 1.8 × 10−15). The most significant genetic correlation of childhood maltreatment was with depressive symptoms (rg = 0.70, p = 4.65 × 10−40), although we show evidence that our top hits may be specific to childhood maltreatment. This is the first large-scale genetic study to identify specific variants associated with self-reported childhood maltreatment. Speculatively, FOXP genes might influence externalizing traits and so be relevant to childhood maltreatment. Alternatively, these variants may be associated with a greater likelihood of reporting maltreatment. A clearer understanding of the genetic relationships of childhood maltreatment, including particular abuse subtypes, with a range of phenotypes, may ultimately be useful in in developing targeted treatment and prevention strategies.

Copyright information:

© The Author(s) 2020.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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