Genomic influences on self-reported childhood maltreatment. Academic Article uri icon

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=4.3510-8, FOXP1; rs10262462, p=3.2410-8, 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=1.810-15). The most significant genetic correlation of childhood maltreatment was with depressive symptoms (rg=0.70, p=4.6510-40), 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.

published proceedings

  • Transl Psychiatry

altmetric score

  • 54.85

author list (cited authors)

  • Dalvie, S., Maihofer, A. X., Coleman, J., Bradley, B., Breen, G., Brick, L. A., ... Nievergelt, C. M.

citation count

  • 33

complete list of authors

  • 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

publication date

  • January 2020