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Genomic influences on self-reported childhood maltreatment
- 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
- et al.
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.
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