Genomic influences on self-reported childhood maltreatment
Authors: 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. , Farrer Lindsay A. , Feeny Norah C. , Flory Janine D. , Forbes David , Galea Sandro , Gautam Aarti , Gelernter Joel , Hammamieh Rasha , Jett Marti , Junglen Angela G. , Kaufman Milissa L. , Kessler Ronald C. , Khan Alaptagin , Kranzler Henry R. , Lebois Lauren A. M. , Marmar Charles , Mavissakalian Matig R. , McFarlane Alexander , Donnell Meaghan O’ , Orcutt Holly K. , Pietrzak Robert H. , Risbrough Victoria B. , Roberts Andrea L. , Rothbaum Alex O. , Roy-Byrne Peter , Ruggiero Ken , Seligowski Antonia V. , Sheerin Christina M. , Silove Derrick , Smoller Jordan W. , Stein Murray B. , Teicher Martin H. , Ursano Robert J. , Van Hooff Miranda , Winternitz Sherry , Wolff Jonathan D. , Yehuda Rachel , Zhao Hongyu , Zoellner Lori A. , Stein Dan J. , Koenen Karestan C. , Nievergelt Caroline M. 
Published: February 2020

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.