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The role of polygenic risk score gene-set analysis in the context of the omnigenic model of schizophrenia

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The role of polygenic risk score gene-set analysis in the context of the omnigenic model of schizophrenia. / Schizophrenia Working Group of the Psychiatric Genomics Consortium 2,.

In: Neuropsychopharmacology, Vol. 44, No. 9, 01.08.2019, p. 1562-1569.

Research output: Contribution to journalJournal article

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Schizophrenia Working Group of the Psychiatric Genomics Consortium 2, 2019, 'The role of polygenic risk score gene-set analysis in the context of the omnigenic model of schizophrenia', Neuropsychopharmacology, vol. 44, no. 9, pp. 1562-1569. https://doi.org/10.1038/s41386-019-0410-z

APA

Schizophrenia Working Group of the Psychiatric Genomics Consortium 2, (2019). The role of polygenic risk score gene-set analysis in the context of the omnigenic model of schizophrenia. Neuropsychopharmacology, 44(9), 1562-1569. https://doi.org/10.1038/s41386-019-0410-z

Vancouver

Schizophrenia Working Group of the Psychiatric Genomics Consortium 2,. The role of polygenic risk score gene-set analysis in the context of the omnigenic model of schizophrenia. Neuropsychopharmacology. 2019 Aug 1;44(9):1562-1569. https://doi.org/10.1038/s41386-019-0410-z

Author

Schizophrenia Working Group of the Psychiatric Genomics Consortium 2,. / The role of polygenic risk score gene-set analysis in the context of the omnigenic model of schizophrenia. In: Neuropsychopharmacology. 2019 ; Vol. 44, No. 9. pp. 1562-1569.

Bibtex

@article{6599ba50b2c9444398098855f96002ed,
title = "The role of polygenic risk score gene-set analysis in the context of the omnigenic model of schizophrenia",
abstract = "A recent development in the genetic architecture of schizophrenia suggested that an omnigenic model may underlie the risk for this disorder. The aim of our study was to use polygenic profile scoring to quantitatively assess whether a number of experimentally derived sets would contribute to the disorder above and beyond the omnigenic effect. Using the PGC2 secondary analysis schizophrenia case-control cohort (N = 29,125 cases and 34,836 controls), a robust polygenic signal was observed from gene sets based on TCF4, FMR1, upregulation from MIR137 and downregulation from CHD8. Additional analyses revealed a constant floor effect in the amount of variance explained, consistent with the omnigenic model. Thus, we report that putative core gene sets showed a significant effect above and beyond the floor effect that might be linked with the underlying omnigenic background. In addition, we demonstrate a method to quantify the contribution of specific gene sets within the omnigenic context.",
author = "{Schizophrenia Working Group of the Psychiatric Genomics Consortium 2,} and Alexandros Rammos and Gonzalez, {Lara A Neira} and Weinberger, {Daniel R} and Mitchell, {Kevin J} and Nicodemus, {Kristin K} and Jo Knight",
year = "2019",
month = aug
day = "1",
doi = "10.1038/s41386-019-0410-z",
language = "English",
volume = "44",
pages = "1562--1569",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "9",

}

RIS

TY - JOUR

T1 - The role of polygenic risk score gene-set analysis in the context of the omnigenic model of schizophrenia

AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium 2,

AU - Rammos, Alexandros

AU - Gonzalez, Lara A Neira

AU - Weinberger, Daniel R

AU - Mitchell, Kevin J

AU - Nicodemus, Kristin K

AU - Knight, Jo

PY - 2019/8/1

Y1 - 2019/8/1

N2 - A recent development in the genetic architecture of schizophrenia suggested that an omnigenic model may underlie the risk for this disorder. The aim of our study was to use polygenic profile scoring to quantitatively assess whether a number of experimentally derived sets would contribute to the disorder above and beyond the omnigenic effect. Using the PGC2 secondary analysis schizophrenia case-control cohort (N = 29,125 cases and 34,836 controls), a robust polygenic signal was observed from gene sets based on TCF4, FMR1, upregulation from MIR137 and downregulation from CHD8. Additional analyses revealed a constant floor effect in the amount of variance explained, consistent with the omnigenic model. Thus, we report that putative core gene sets showed a significant effect above and beyond the floor effect that might be linked with the underlying omnigenic background. In addition, we demonstrate a method to quantify the contribution of specific gene sets within the omnigenic context.

AB - A recent development in the genetic architecture of schizophrenia suggested that an omnigenic model may underlie the risk for this disorder. The aim of our study was to use polygenic profile scoring to quantitatively assess whether a number of experimentally derived sets would contribute to the disorder above and beyond the omnigenic effect. Using the PGC2 secondary analysis schizophrenia case-control cohort (N = 29,125 cases and 34,836 controls), a robust polygenic signal was observed from gene sets based on TCF4, FMR1, upregulation from MIR137 and downregulation from CHD8. Additional analyses revealed a constant floor effect in the amount of variance explained, consistent with the omnigenic model. Thus, we report that putative core gene sets showed a significant effect above and beyond the floor effect that might be linked with the underlying omnigenic background. In addition, we demonstrate a method to quantify the contribution of specific gene sets within the omnigenic context.

U2 - 10.1038/s41386-019-0410-z

DO - 10.1038/s41386-019-0410-z

M3 - Journal article

C2 - 31078131

VL - 44

SP - 1562

EP - 1569

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 9

ER -