Genomic influences on self-reported childhood maltreatment

Media type: E-Article

Title: Genomic influences on self-reported childhood maltreatment

Contributor: Dalvie, Shareefa; Maihofer, Adam X.; Coleman, Jonathan R. I.; Bradley, Bekh; Breen, Gerome; Brick, Leslie A.; Chen, Chia-Yen; Choi, Karmel W.; Duncan, Laramie E.; Guffanti, Guia; Haas, Magali; Harnal, Supriya; Liberzon, Israel; Nugent, Nicole R.; Provost, Allison C.; Ressler, Kerry J.; Torres, Katy; Amstadter, Ananda B.; Bryn Austin, S.; Baker, Dewleen G.; Bolger, Elizabeth A.; Bryant, Richard A.; Calabrese, Joseph R.; Delahanty, Douglas L.; [...]

Published: Springer Science and Business Media LLC, 2020

Language: English

DOI: 10.1038/s41398-020-0706-0

ISSN: 2158-3188

Origination:

Footnote:

Description: AbstractChildhood 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.

Access State: Open Access

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