TY  - JOUR
PY  - 2020//
TI  - Genomic influences on self-reported childhood maltreatment
JO  - Translational psychiatry
A1  - Dalvie, Shareefa
A1  - Maihofer, Adam X.
A1  - Coleman, Jonathan R. I.
A1  - Bradley, Bekh
A1  - Breen, Gerome
A1  - Brick, Leslie Ann
A1  - Chen, Chia-Yen
A1  - Choi, Karmel W.
A1  - Duncan, Laramie E.
A1  - Guffanti, Guia
A1  - Haas, Magali
A1  - Harnal, Supriya
A1  - Liberzon, Israel
A1  - Nugent, Nicole R.
A1  - Provost, Allison C.
A1  - Ressler, Kerry J.
A1  - Torres, Katy
A1  - Amstadter, Ananda B.
A1  - Bryn Austin, S.
A1  - Baker, Dewleen G.
A1  - Bolger, Elizabeth A.
A1  - Bryant, Richard A.
A1  - Calabrese, Joseph R.
A1  - Delahanty, Douglas L.
A1  - Farrer, Lindsay A.
A1  - Feeny, Norah C.
A1  - Flory, Janine D.
A1  - Forbes, David
A1  - Galea, Sandro
A1  - Gautam, Aarti
A1  - Gelernter, Joel
A1  - Hammamieh, Rasha
A1  - Jett, Marti
A1  - Junglen, Angela G.
A1  - Kaufman, Milissa L.
A1  - Kessler, Ronald C.
A1  - Khan, Alaptagin
A1  - Kranzler, Henry R.
A1  - Lebois, Lauren A. M.
A1  - Marmar, Charles
A1  - Mavissakalian, Matig R.
A1  - McFarlane, Alexander
A1  - Donnell, Meaghan O'
A1  - Orcutt, Holly K.
A1  - Pietrzak, Robert H.
A1  - Risbrough, Victoria B.
A1  - Roberts, Andrea L.
A1  - Rothbaum, Alex O.
A1  - Roy-Byrne, Peter P.
A1  - Ruggiero, Ken
A1  - Seligowski, Antonia V.
A1  - Sheerin, Christina M.
A1  - Silove, Derrick
A1  - Smoller, Jordan W.
A1  - Stein, Murray B.
A1  - Teicher, Martin H.
A1  - Ursano, Robert J.
A1  - Van Hooff, Miranda
A1  - Winternitz, Sherry
A1  - Wolff, Jonathan D.
A1  - Yehuda, Rachel
A1  - Zhao, Hongyu
A1  - Zoellner, Lori A.
A1  - Stein, Dan J.
A1  - Koenen, Karestan C.
A1  - Nievergelt, Caroline M.
SP  - e38
EP  - e38
VL  - 10
IS  - 1
N2  - 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<sup>2</sup><sub>snp</sub>), (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<sup>2</sup><sub>snp</sub> 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<sup>-8</sup>, FOXP1; rs10262462, p = 3.24 × 10<sup>-8</sup>, FOXP2) were identified in the discovery dataset but were not replicated in PGC-PTSD. h<sup>2</sup><sub>snp</sub> for childhood maltreatment was ~6% and the PRS derived from the UKBB was significantly predictive of childhood maltreatment in PGC-PTSD (r<sup>2</sup> = 0.0025; p = 1.8 × 10<sup>-15</sup>). The most significant genetic correlation of childhood maltreatment was with depressive symptoms (r<sub>g</sub> = 0.70, p = 4.65 × 10<sup>-40</sup>), 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.<p />  <p>Language: en</p>
LA  - en
SN  - 2158-3188
UR  - http://dx.doi.org/10.1038/s41398-020-0706-0
ID  - ref1
ER  -