| Title: | Genomic influences on self-reported childhood maltreatment |
| Journal: | Translational Psychiatry |
| Published: | 27 Jan 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32066696/ |
| DOI: | https://doi.org/10.1038/s41398-020-0706-0 |
| URL: | https://escholarship.org/uc/item/7v35b96p |
| Citations: | 50 (17 in last 2 years) as of 8 Aug 2024 |
Publication 9091
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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.</p>
10 Keywords
- Child
- Child Abuse
- Forkhead Transcription Factors
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Genomics
- Humans
- Repressor Proteins
- Self Report
- Stress Disorders, Post-Traumatic
66 Authors
- Shareefa Dalvie
- Adam X. Maihofer
- Jonathan R. I. Coleman
- Bekh Bradley
- Gerome Breen
- Leslie A. Brick
- Chia-Yen Chen
- Karmel W. Choi
- Laramie E. Duncan
- Guia Guffanti
- Magali Haas
- Supriya Harnal
- Israel Liberzon
- Nicole R. Nugent
- Allison C. Provost
- Kerry J. Ressler
- Katy Torres
- Ananda B. Amstadter
- S. Bryn Austin
- Dewleen G. Baker
- Elizabeth A. Bolger
- Richard A. Bryant
- Joseph R. Calabrese
- Douglas L. Delahanty
- Lindsay A. Farrer
- Norah C. Feeny
- Janine D. Flory
- David Forbes
- Sandro Galea
- Aarti Gautam
- Joel Gelernter
- Rasha Hammamieh
- Marti Jett
- Angela G. Junglen
- Milissa L. Kaufman
- Ronald C. Kessler
- Alaptagin Khan
- Henry R. Kranzler
- Lauren A. M. Lebois
- Charles Marmar
- Matig R. Mavissakalian
- Alexander McFarlane
- Meaghan O' Donnell
- Holly K. Orcutt
- Robert H. Pietrzak
- Victoria B. Risbrough
- Andrea L. Roberts
- Alex O. Rothbaum
- Peter Roy-Byrne
- Ken Ruggiero
- Antonia V. Seligowski
- Christina M. Sheerin
- Derrick Silove
- Jordan W. Smoller
- Murray B. Stein
- Martin H. Teicher
- Robert J. Ursano
- Miranda Van Hooff
- Sherry Winternitz
- Jonathan D. Wolff
- Rachel Yehuda
- Hongyu Zhao
- Lori A. Zoellner
- Dan J. Stein
- Karestan C. Koenen
- Caroline M. Nievergelt
1 Application
| Application ID | Title |
|---|---|
| 16577 | Investigations of the genetic overlap between internalising psychiatric disorders and co-morbid physical health disorders. |
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