Genomic influences on self-reported childhood maltreatment

Shareefa Dalvie; Adam X. Maihofer; Jonathan R.I. Coleman; Bekh Bradley; Gerome Breen; Leslie A. Brick; Chia Yen Chen; Karmel W. Choi; Laramie E. Duncan; Guia Guffanti; Magali Haas; Supriya Harnal; Israel Liberzon; Nicole R. Nugent; Allison C. Provost; Kerry J. Ressler; Katy Torres; Ananda B. Amstadter; S. Bryn Austin; Dewleen G. Baker; Elizabeth A. Bolger; Richard A. Bryant; Joseph R. Calabrese; Douglas L. Delahanty; Lindsay A. Farrer; Norah C. Feeny; Janine D. Flory; David Forbes; Sandro Galea; Aarti Gautam; Joel Gelernter; Rasha Hammamieh; Marti Jett; Angela G. Junglen; Milissa L. Kaufman; Ronald C. Kessler; Alaptagin Khan; Henry R. Kranzler; Lauren A.M. Lebois; Charles Marmar; Matig R. Mavissakalian; Alexander McFarlane; Meaghan O’ Donnell; Holly K. Orcutt; Robert H. Pietrzak; Victoria B. Risbrough; Andrea L. Roberts; Alex O. Rothbaum; Peter Roy-Byrne; Ken Ruggiero; Antonia V. Seligowski; Christina M. Sheerin; Derrick Silove; Jordan W. Smoller; Murray B. Stein; Martin H. Teicher; Robert J. Ursano; Miranda Van Hooff; Sherry Winternitz; Jonathan D. Wolff; Rachel Yehuda; Hongyu Zhao; Lori A. Zoellner; Dan J. Stein; Karestan C. Koenen; Caroline M. Nievergelt

doi:10.1038/s41398-020-0706-0

Genomic influences on self-reported childhood maltreatment

Shareefa Dalvie, Adam X. Maihofer, Jonathan R.I. Coleman, Bekh Bradley, Gerome Breen, Leslie A. Brick, Chia Yen Chen, Karmel W. Choi, Laramie E. Duncan, Guia Guffanti, Magali Haas, Supriya Harnal, Israel Liberzon, Nicole R. Nugent, Allison C. Provost, Kerry J. Ressler, Katy Torres, Ananda B. Amstadter, S. Bryn Austin, Dewleen G. BakerElizabeth A. Bolger, Richard A. Bryant, Joseph R. Calabrese, Douglas L. Delahanty, Lindsay A. Farrer, Norah C. Feeny, Janine D. Flory, David Forbes, Sandro Galea, Aarti Gautam, Joel Gelernter, Rasha Hammamieh, Marti Jett, Angela G. Junglen, Milissa L. Kaufman, Ronald C. Kessler, Alaptagin Khan, Henry R. Kranzler, Lauren A.M. Lebois, Charles Marmar, Matig R. Mavissakalian, Alexander McFarlane, Meaghan O’ Donnell, Holly K. Orcutt, Robert H. Pietrzak, Victoria B. Risbrough, Andrea L. Roberts, Alex O. Rothbaum, Peter Roy-Byrne, Ken Ruggiero, Antonia V. Seligowski, Christina M. Sheerin, Derrick Silove, Jordan W. Smoller, Murray B. Stein, Martin H. Teicher, Robert J. Ursano, Miranda Van Hooff, Sherry Winternitz, Jonathan D. Wolff, Rachel Yehuda, Hongyu Zhao, Lori A. Zoellner, Dan J. Stein, Karestan C. Koenen, Caroline M. Nievergelt

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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 (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 (r_g = 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.

Original language	English (US)
Article number	38
Pages (from-to)	38
Journal	Translational Psychiatry
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41398-020-0706-0
State	Published - Jan 27 2020

ASJC Scopus subject areas

Psychiatry and Mental health
Cellular and Molecular Neuroscience
Biological Psychiatry

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Dalvie, S., Maihofer, A. X., Coleman, J. R. I., Bradley, B., Breen, G., Brick, L. A., Chen, C. Y., Choi, K. W., Duncan, L. E., Guffanti, G., Haas, M., Harnal, S., Liberzon, I., Nugent, N. R., Provost, A. C., Ressler, K. J., Torres, K., Amstadter, A. B., Bryn Austin, S., ... Nievergelt, C. M. (2020). Genomic influences on self-reported childhood maltreatment. Translational Psychiatry, 10(1), 38. Article 38. https://doi.org/10.1038/s41398-020-0706-0

Dalvie, S, Maihofer, AX, Coleman, JRI, Bradley, B, Breen, G, Brick, LA, Chen, CY, Choi, KW, Duncan, LE, Guffanti, G, Haas, M, Harnal, S, Liberzon, I, Nugent, NR, Provost, AC, Ressler, KJ, Torres, K, Amstadter, AB, Bryn Austin, S, Baker, DG, Bolger, EA, Bryant, RA, Calabrese, JR, Delahanty, DL, Farrer, LA, Feeny, NC, Flory, JD, Forbes, D, Galea, S, Gautam, A, Gelernter, J, Hammamieh, R, Jett, M, Junglen, AG, Kaufman, ML, Kessler, RC, Khan, A, Kranzler, HR, Lebois, LAM, Marmar, C, Mavissakalian, MR, McFarlane, A, Donnell, MO, Orcutt, HK, Pietrzak, RH, Risbrough, VB, Roberts, AL, Rothbaum, AO, Roy-Byrne, P, Ruggiero, K, Seligowski, AV, Sheerin, CM, Silove, D, Smoller, JW, Stein, MB, Teicher, MH, Ursano, RJ, Van Hooff, M, Winternitz, S, Wolff, JD, Yehuda, R, Zhao, H, Zoellner, LA, Stein, DJ, Koenen, KC & Nievergelt, CM 2020, 'Genomic influences on self-reported childhood maltreatment', Translational Psychiatry, vol. 10, no. 1, 38, pp. 38. https://doi.org/10.1038/s41398-020-0706-0

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title = "Genomic influences on self-reported childhood maltreatment",

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 (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.",

author = "Shareefa Dalvie and Maihofer, {Adam X.} and Coleman, {Jonathan R.I.} and Bekh Bradley and Gerome Breen and Brick, {Leslie A.} and Chen, {Chia Yen} and Choi, {Karmel W.} and Duncan, {Laramie E.} and Guia Guffanti and Magali Haas and Supriya Harnal and Israel Liberzon and Nugent, {Nicole R.} and Provost, {Allison C.} and Ressler, {Kerry J.} and Katy Torres and Amstadter, {Ananda B.} and {Bryn Austin}, S. and Baker, {Dewleen G.} and Bolger, {Elizabeth A.} and Bryant, {Richard A.} and Calabrese, {Joseph R.} and Delahanty, {Douglas L.} and Farrer, {Lindsay A.} and Feeny, {Norah C.} and Flory, {Janine D.} and David Forbes and Sandro Galea and Aarti Gautam and Joel Gelernter and Rasha Hammamieh and Marti Jett and Junglen, {Angela G.} and Kaufman, {Milissa L.} and Kessler, {Ronald C.} and Alaptagin Khan and Kranzler, {Henry R.} and Lebois, {Lauren A.M.} and Charles Marmar and Mavissakalian, {Matig R.} and Alexander McFarlane and Donnell, {Meaghan O{\textquoteright}} and Orcutt, {Holly K.} and Pietrzak, {Robert H.} and Risbrough, {Victoria B.} and Roberts, {Andrea L.} and Rothbaum, {Alex O.} and Peter Roy-Byrne and Ken Ruggiero and Seligowski, {Antonia V.} and Sheerin, {Christina M.} and Derrick Silove and Smoller, {Jordan W.} and Stein, {Murray B.} and Teicher, {Martin H.} and Ursano, {Robert J.} and {Van Hooff}, Miranda and Sherry Winternitz and Wolff, {Jonathan D.} and Rachel Yehuda and Hongyu Zhao and Zoellner, {Lori A.} and Stein, {Dan J.} and Koenen, {Karestan C.} and Nievergelt, {Caroline M.}",

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doi = "10.1038/s41398-020-0706-0",

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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.

PY - 2020/1/27

Y1 - 2020/1/27

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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Genomic influences on self-reported childhood maltreatment

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