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Genomic influences on self-reported childhood maltreatment.

  • Author(s): 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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