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. , Austin S. Bryn , 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 , O’Donnell Meaghan , Orcutt Holly K. , Pietrzak Robert H. , Risbrough Victoria B. , Roberts Andrea L. , Rothbaum Alex O. , Roy-Byrne P. , Ruggiero Ken , Seligowski Antonia V. , Sheerin Christina M. , Silove Derrick , Smoller Jordan W. , Solovieff Nadia , 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: July 2019

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 reported childhood maltreatment, 2) calculate the relevant SNP-based heritability estimates, and 3) quantify the genetic overlap of reported childhood maltreatment with mental and physical health-related phenotypes. 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 working group (PGC-PTSD) (n=26,290). Heritability estimations for childhood maltreatment and genetic correlations with mental/physical health traits were calculated using linkage disequilibrium score regression (LDSR). Two genome-wide significant loci associated with childhood maltreatment, located on chromosomes 3p13 (rs142346759, beta=0.015, p=4.35×10−8,FOXP1) and 7q31.1 (rs10262462, beta=-0.016, p=3.24×10−8,FOXP2), were identified in the discovery dataset but were not replicated in the PGC-PTSD sample. SNP-based heritability for childhood maltreatment was estimated to be ∼6%. Childhood maltreatment was most significantly genetically correlated with depressive symptoms (rg=0.70, p=4.65×10−40). This is the first large-scale genetic study to identify specific variants associated with self-reported childhood maltreatment.FOXPgenes could influence traits such as depression and thereby 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 various psychiatric disorders, may ultimately be useful in in developing targeted treatment and prevention strategies.