Genomic influences on self-reported childhood maltreatment.

Genomic influences on self-reported childhood maltreatment.

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;
Translational Psychiatry 2020 Vol. 10 pp. 38
186
dalvie2020genomictranslational

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

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