Department of Economics and Business Economics

A polygenic resilience score moderates the genetic risk for schizophrenia

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A polygenic resilience score moderates the genetic risk for schizophrenia. / Hess, Jonathan L; Tylee, Daniel S; Mattheisen, Manuel; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) ; Børglum, Anders D; Als, Thomas D; Grove, Jakob; Werge, Thomas; Mortensen, Preben Bo; Mors, Ole; Nordentoft, Merete; Hougaard, David M; Byberg-Grauholm, Jonas; Bækvad-Hansen, Marie; Greenwood, Tiffany A; Tsuang, Ming T; Curtis, David; Steinberg, Stacy; Sigurdsson, Engilbert; Stefánsson, Hreinn; Stefánsson, Kári; Edenberg, Howard J; Holmans, Peter; Faraone, Stephen V; Glatt, Stephen J.

In: Molecular Psychiatry, Vol. 26, No. 3, 03.2021, p. 800–815.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Hess, JL, Tylee, DS, Mattheisen, M, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Børglum, AD, Als, TD, Grove, J, Werge, T, Mortensen, PB, Mors, O, Nordentoft, M, Hougaard, DM, Byberg-Grauholm, J, Bækvad-Hansen, M, Greenwood, TA, Tsuang, MT, Curtis, D, Steinberg, S, Sigurdsson, E, Stefánsson, H, Stefánsson, K, Edenberg, HJ, Holmans, P, Faraone, SV & Glatt, SJ 2021, 'A polygenic resilience score moderates the genetic risk for schizophrenia', Molecular Psychiatry, vol. 26, no. 3, pp. 800–815. https://doi.org/10.1038/s41380-019-0463-8

APA

Hess, J. L., Tylee, D. S., Mattheisen, M., Schizophrenia Working Group of the Psychiatric Genomics Consortium, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Børglum, A. D., Als, T. D., Grove, J., Werge, T., Mortensen, P. B., Mors, O., Nordentoft, M., Hougaard, D. M., Byberg-Grauholm, J., Bækvad-Hansen, M., Greenwood, T. A., Tsuang, M. T., Curtis, D., Steinberg, S., ... Glatt, S. J. (2021). A polygenic resilience score moderates the genetic risk for schizophrenia. Molecular Psychiatry, 26(3), 800–815. https://doi.org/10.1038/s41380-019-0463-8

CBE

Hess JL, Tylee DS, Mattheisen M, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Børglum AD, Als TD, Grove J, Werge T, Mortensen PB, Mors O, Nordentoft M, Hougaard DM, Byberg-Grauholm J, Bækvad-Hansen M, Greenwood TA, Tsuang MT, Curtis D, Steinberg S, Sigurdsson E, Stefánsson H, Stefánsson K, Edenberg HJ, Holmans P, Faraone SV, Glatt SJ. 2021. A polygenic resilience score moderates the genetic risk for schizophrenia. Molecular Psychiatry. 26(3):800–815. https://doi.org/10.1038/s41380-019-0463-8

MLA

Vancouver

Hess JL, Tylee DS, Mattheisen M, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Børglum AD et al. A polygenic resilience score moderates the genetic risk for schizophrenia. Molecular Psychiatry. 2021 Mar;26(3):800–815. https://doi.org/10.1038/s41380-019-0463-8

Author

Hess, Jonathan L ; Tylee, Daniel S ; Mattheisen, Manuel ; Schizophrenia Working Group of the Psychiatric Genomics Consortium ; Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) ; Børglum, Anders D ; Als, Thomas D ; Grove, Jakob ; Werge, Thomas ; Mortensen, Preben Bo ; Mors, Ole ; Nordentoft, Merete ; Hougaard, David M ; Byberg-Grauholm, Jonas ; Bækvad-Hansen, Marie ; Greenwood, Tiffany A ; Tsuang, Ming T ; Curtis, David ; Steinberg, Stacy ; Sigurdsson, Engilbert ; Stefánsson, Hreinn ; Stefánsson, Kári ; Edenberg, Howard J ; Holmans, Peter ; Faraone, Stephen V ; Glatt, Stephen J. / A polygenic resilience score moderates the genetic risk for schizophrenia. In: Molecular Psychiatry. 2021 ; Vol. 26, No. 3. pp. 800–815.

Bibtex

@article{772e0ff581fb4f5eb4ac5246c168829e,
title = "A polygenic resilience score moderates the genetic risk for schizophrenia",
abstract = "Based on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531-538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable polygenic disorders1,0 such as schizophrenia. Resilience has been traditionally viewed as a psychological construct, although our use of the term resilience refers to a different construct that directly relates to the Resilience Project, namely: heritable variation that promotes resistance to disease by reducing the penetrance of risk loci, wherein resilience and risk loci operate orthogonal to one another. In this study, we established a procedure to identify unaffected individuals with relatively high polygenic risk for schizophrenia, and contrasted them with risk-matched schizophrenia cases to generate the first known {"}polygenic resilience score{"} that represents the additive contributions to SZ resistance by variants that are distinct from risk loci. The resilience score was derived from data compiled by the Psychiatric Genomics Consortium, and replicated in three independent samples. This work establishes a generalizable framework for finding resilience variants for any complex, heritable disorder.",
author = "Hess, {Jonathan L} and Tylee, {Daniel S} and Manuel Mattheisen and {Schizophrenia Working Group of the Psychiatric Genomics Consortium} and {Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH)} and B{\o}rglum, {Anders D} and Als, {Thomas D} and Jakob Grove and Thomas Werge and Mortensen, {Preben Bo} and Ole Mors and Merete Nordentoft and Hougaard, {David M} and Jonas Byberg-Grauholm and Marie B{\ae}kvad-Hansen and Greenwood, {Tiffany A} and Tsuang, {Ming T} and David Curtis and Stacy Steinberg and Engilbert Sigurdsson and Hreinn Stef{\'a}nsson and K{\'a}ri Stef{\'a}nsson and Edenberg, {Howard J} and Peter Holmans and Faraone, {Stephen V} and Glatt, {Stephen J}",
year = "2021",
month = mar,
doi = "10.1038/s41380-019-0463-8",
language = "English",
volume = "26",
pages = "800–815",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "3",

}

RIS

TY - JOUR

T1 - A polygenic resilience score moderates the genetic risk for schizophrenia

AU - Hess, Jonathan L

AU - Tylee, Daniel S

AU - Mattheisen, Manuel

AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium

AU - Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH)

AU - Børglum, Anders D

AU - Als, Thomas D

AU - Grove, Jakob

AU - Werge, Thomas

AU - Mortensen, Preben Bo

AU - Mors, Ole

AU - Nordentoft, Merete

AU - Hougaard, David M

AU - Byberg-Grauholm, Jonas

AU - Bækvad-Hansen, Marie

AU - Greenwood, Tiffany A

AU - Tsuang, Ming T

AU - Curtis, David

AU - Steinberg, Stacy

AU - Sigurdsson, Engilbert

AU - Stefánsson, Hreinn

AU - Stefánsson, Kári

AU - Edenberg, Howard J

AU - Holmans, Peter

AU - Faraone, Stephen V

AU - Glatt, Stephen J

PY - 2021/3

Y1 - 2021/3

N2 - Based on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531-538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable polygenic disorders1,0 such as schizophrenia. Resilience has been traditionally viewed as a psychological construct, although our use of the term resilience refers to a different construct that directly relates to the Resilience Project, namely: heritable variation that promotes resistance to disease by reducing the penetrance of risk loci, wherein resilience and risk loci operate orthogonal to one another. In this study, we established a procedure to identify unaffected individuals with relatively high polygenic risk for schizophrenia, and contrasted them with risk-matched schizophrenia cases to generate the first known "polygenic resilience score" that represents the additive contributions to SZ resistance by variants that are distinct from risk loci. The resilience score was derived from data compiled by the Psychiatric Genomics Consortium, and replicated in three independent samples. This work establishes a generalizable framework for finding resilience variants for any complex, heritable disorder.

AB - Based on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531-538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable polygenic disorders1,0 such as schizophrenia. Resilience has been traditionally viewed as a psychological construct, although our use of the term resilience refers to a different construct that directly relates to the Resilience Project, namely: heritable variation that promotes resistance to disease by reducing the penetrance of risk loci, wherein resilience and risk loci operate orthogonal to one another. In this study, we established a procedure to identify unaffected individuals with relatively high polygenic risk for schizophrenia, and contrasted them with risk-matched schizophrenia cases to generate the first known "polygenic resilience score" that represents the additive contributions to SZ resistance by variants that are distinct from risk loci. The resilience score was derived from data compiled by the Psychiatric Genomics Consortium, and replicated in three independent samples. This work establishes a generalizable framework for finding resilience variants for any complex, heritable disorder.

UR - http://www.scopus.com/inward/record.url?scp=85073941184&partnerID=8YFLogxK

U2 - 10.1038/s41380-019-0463-8

DO - 10.1038/s41380-019-0463-8

M3 - Journal article

C2 - 31492941

VL - 26

SP - 800

EP - 815

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 3

ER -