TY - JOUR
T1 - Genomic influences on self-reported childhood maltreatment
AU - Dalvie, Shareefa
AU - Maihofer, Adam X.
AU - Coleman, Jonathan R.I.
AU - Bradley, Bekh
AU - Breen, Gerome
AU - Brick, Leslie A.
AU - Chen, Chia Yen
AU - Choi, Karmel W.
AU - Duncan, Laramie E.
AU - Guffanti, Guia
AU - Haas, Magali
AU - Harnal, Supriya
AU - Liberzon, Israel
AU - Nugent, Nicole R.
AU - Provost, Allison C.
AU - Ressler, Kerry J.
AU - Torres, Katy
AU - Amstadter, Ananda B.
AU - Bryn Austin, S.
AU - Baker, Dewleen G.
AU - Bolger, Elizabeth A.
AU - Bryant, Richard A.
AU - Calabrese, Joseph R.
AU - Delahanty, Douglas L.
AU - Farrer, Lindsay A.
AU - Feeny, Norah C.
AU - Flory, Janine D.
AU - Forbes, David
AU - Galea, Sandro
AU - Gautam, Aarti
AU - Gelernter, Joel
AU - Hammamieh, Rasha
AU - Jett, Marti
AU - Junglen, Angela G.
AU - Kaufman, Milissa L.
AU - Kessler, Ronald C.
AU - Khan, Alaptagin
AU - Kranzler, Henry R.
AU - Lebois, Lauren A.M.
AU - Marmar, Charles
AU - Mavissakalian, Matig R.
AU - McFarlane, Alexander
AU - Donnell, Meaghan O’
AU - Orcutt, Holly K.
AU - Pietrzak, Robert H.
AU - Risbrough, Victoria B.
AU - Roberts, Andrea L.
AU - Rothbaum, Alex O.
AU - Roy-Byrne, Peter
AU - Ruggiero, Ken
AU - Seligowski, Antonia V.
AU - Sheerin, Christina M.
AU - Silove, Derrick
AU - Smoller, Jordan W.
AU - Stein, Murray B.
AU - Teicher, Martin H.
AU - Ursano, Robert J.
AU - Van Hooff, Miranda
AU - Winternitz, Sherry
AU - Wolff, Jonathan D.
AU - Yehuda, Rachel
AU - Zhao, Hongyu
AU - Zoellner, Lori A.
AU - Stein, Dan J.
AU - Koenen, Karestan C.
AU - Nievergelt, Caroline M.
N1 - Funding Information:
H.R.K. is a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative (ACTIVE), which in the last 3 years was supported by AbbVie, Alkermes, Amygdala Neurosciences, Arbor, Ethypharm, Indivior, Lilly, Lundbeck, Otsuka, and Pfizer. H.R.K. and J.G. are named as inventors on PCT patent application #15/878,640 entitled: “Genotype-guided dosing of opioid agonists,” filed January 24, 2018. In the past 3 years, D.J.S. has received research grants and/or consultancy honoraria from Lundbeck and Sun. In the past 3 years, R.C.K. received support for his epidemiological studies from Sanofi Aventis; was a consultant for Johnson & Johnson Wellness and Prevention, Sage Pharmaceuticals, Shire, Takeda; and served on an advisory board for the Johnson & Johnson. Services Inc. Lake Nona Life Project. Kessler is a co-owner of DataStat, Inc., a market research firm that carries out healthcare research. M.B.S. has in the past 3 years been a consultant for Aptinyx, Bionomics, Dart Neuroscience, Janssen, Jazz Pharmaceuticals, Neurocrine Biosciences, Oxeia Biopharmaceuticals, and Pfizer. R.Y. is a co-inventor of the following patent application: “Genes associated with posttraumatic-stress disorder. European Patent# EP 2334816 B1.
Funding Information:
This work was funded by Cohen Veterans Bioscience, the NIMH/U.S. Army Medical Research and Materiel Command Grant R01MH106595 to C.M.N., I.L., K.J.R. and K.C.K., One Mind, and supported by 5U01MH109539 to the Psychiatric Genomics Consortium. Statistical Analysis were carried out on the NL Genetic Cluster computer (URL) hosted by SURFsara. Genotyping of samples was supported in part through the Stanley Center for Psychiatric Genetics at the Broad Institute of MIT and Harvard. This research has been conducted using the UK biobank resource under application number 16577.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
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 (h2 snp), (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). h2 snp 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. h2 snp 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.
AB - 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 (h2 snp), (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). h2 snp 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. h2 snp 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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U2 - 10.1038/s41398-020-0706-0
DO - 10.1038/s41398-020-0706-0
M3 - Article
C2 - 32066696
AN - SCOPUS:85079648385
VL - 10
JO - Translational Psychiatry
JF - Translational Psychiatry
SN - 2158-3188
IS - 1
M1 - 38
ER -