학술논문
Genomic influences on self-reported childhood maltreatment
Document Type
article
Author
Dalvie, Shareefa; Maihofer, Adam X; Coleman, Jonathan RI; 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 AM; 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
Source
Translational Psychiatry. 10(1)
Subject
Language
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.