Genomic influences on self-reported childhood maltreatment

摘要

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 (hsup2/supsubsnp/sub), (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). hsup2/supsubsnp/sub 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?×?10sup-8/sup, FOXP1; rs10262462, p?=?3.24?×?10sup-8/sup, FOXP2) were identified in the discovery dataset but were not replicated in PGC-PTSD. hsup2/supsubsnp/sub for childhood maltreatment was ~6% and the PRS derived from the UKBB was significantly predictive of childhood maltreatment in PGC-PTSD (rsup2/sup?=?0.0025; p?=?1.8?×?10sup-15/sup). The most significant genetic correlation of childhood maltreatment was with depressive symptoms (rsubg/sub?=?0.70, p?=?4.65?×?10sup-40/sup), 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.