Association of DNA methylation differences with schizophrenia in an epigenome-wide association study

Carolina Montano, Margaret Anne Taub, Andrew Jaffe, Eirikur Briem, Jason I. Feinberg, Rakel Trygvadottir, Adrian Idrizi, Arni Runarsson, Birna Berndsen, Ruben C. Gur, Tyler M. Moore, Rodney T. Perry, Doug Fugman, Sarven Sabunciyan, Robert H Yolken, Thomas Hyde, Joel Kleinman, Janet L. Sobell, Carlos N. Pato, Michele T. PatoRodney C. Go, Vishwajit Nimgaonkar, Daniel Weinberger, David Braff, Raquel E. Gur, Daniele Daniele Fallin, Andrew P Feinberg

Research output: Contribution to journalArticle

Abstract

Importance: DNA methylation may play an important role in schizophrenia (SZ), either directly as a mechanism of pathogenesis or as a biomarker of risk. O. Objective: To scan genome-wide DNA methylation data to identify differentially methylated CpGs between SZ cases and controls. Design, Setting, and Participants: Epigenome-wide association study begun in 2008 using DNA methylation levels of 456 513 CpG loci measured on the Infinium HumanMethylation450 array (Illumina) in a consortium of case-control studies for initial discovery and in an independent replication set. Primary analyses used general linear regression, adjusting for age, sex, race/ethnicity, smoking, batch, and cell type heterogeneity. The discovery set contained 689 SZ cases and 645 controls (n = 1334), from 3 multisite consortia: the Consortium on the Genetics of Endophenotypes in Schizophrenia, the Project among African-Americans To Explore Risks for Schizophrenia, and the Multiplex Multigenerational Family Study of Schizophrenia. The replication set contained 247 SZ cases and 250 controls (n = 497) from the Genomic Psychiatry Cohort. Main Outcomes and Measures: Identification of differentially methylated positions across the genome in SZ cases compared with controls. RESULTS Of the 689 case participants in the discovery set, 477 (69%) were men and 258 (37%) were non-African American; of the 645 controls, 273 (42%) were men and 419 (65%) were non-African American. In our replication set, cases/controls were 76%male and 100% non-African American.We identified SZ-associated methylation differences at 923 CpGs in the discovery set (false discovery rate,

Original languageEnglish (US)
Pages (from-to)506-514
Number of pages9
JournalJAMA Psychiatry
Volume73
Issue number5
DOIs
StatePublished - May 1 2016

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DNA Methylation
Schizophrenia
Genome
Endophenotypes
African Americans
Methylation
Psychiatry
Case-Control Studies
Linear Models
Biomarkers
Smoking
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Psychiatry and Mental health

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Association of DNA methylation differences with schizophrenia in an epigenome-wide association study. / Montano, Carolina; Taub, Margaret Anne; Jaffe, Andrew; Briem, Eirikur; Feinberg, Jason I.; Trygvadottir, Rakel; Idrizi, Adrian; Runarsson, Arni; Berndsen, Birna; Gur, Ruben C.; Moore, Tyler M.; Perry, Rodney T.; Fugman, Doug; Sabunciyan, Sarven; Yolken, Robert H; Hyde, Thomas; Kleinman, Joel; Sobell, Janet L.; Pato, Carlos N.; Pato, Michele T.; Go, Rodney C.; Nimgaonkar, Vishwajit; Weinberger, Daniel; Braff, David; Gur, Raquel E.; Fallin, Daniele Daniele; Feinberg, Andrew P.

In: JAMA Psychiatry, Vol. 73, No. 5, 01.05.2016, p. 506-514.

Research output: Contribution to journalArticle

Montano, C, Taub, MA, Jaffe, A, Briem, E, Feinberg, JI, Trygvadottir, R, Idrizi, A, Runarsson, A, Berndsen, B, Gur, RC, Moore, TM, Perry, RT, Fugman, D, Sabunciyan, S, Yolken, RH, Hyde, T, Kleinman, J, Sobell, JL, Pato, CN, Pato, MT, Go, RC, Nimgaonkar, V, Weinberger, D, Braff, D, Gur, RE, Fallin, DD & Feinberg, AP 2016, 'Association of DNA methylation differences with schizophrenia in an epigenome-wide association study', JAMA Psychiatry, vol. 73, no. 5, pp. 506-514. https://doi.org/10.1001/jamapsychiatry.2016.0144
Montano, Carolina ; Taub, Margaret Anne ; Jaffe, Andrew ; Briem, Eirikur ; Feinberg, Jason I. ; Trygvadottir, Rakel ; Idrizi, Adrian ; Runarsson, Arni ; Berndsen, Birna ; Gur, Ruben C. ; Moore, Tyler M. ; Perry, Rodney T. ; Fugman, Doug ; Sabunciyan, Sarven ; Yolken, Robert H ; Hyde, Thomas ; Kleinman, Joel ; Sobell, Janet L. ; Pato, Carlos N. ; Pato, Michele T. ; Go, Rodney C. ; Nimgaonkar, Vishwajit ; Weinberger, Daniel ; Braff, David ; Gur, Raquel E. ; Fallin, Daniele Daniele ; Feinberg, Andrew P. / Association of DNA methylation differences with schizophrenia in an epigenome-wide association study. In: JAMA Psychiatry. 2016 ; Vol. 73, No. 5. pp. 506-514.
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abstract = "Importance: DNA methylation may play an important role in schizophrenia (SZ), either directly as a mechanism of pathogenesis or as a biomarker of risk. O. Objective: To scan genome-wide DNA methylation data to identify differentially methylated CpGs between SZ cases and controls. Design, Setting, and Participants: Epigenome-wide association study begun in 2008 using DNA methylation levels of 456 513 CpG loci measured on the Infinium HumanMethylation450 array (Illumina) in a consortium of case-control studies for initial discovery and in an independent replication set. Primary analyses used general linear regression, adjusting for age, sex, race/ethnicity, smoking, batch, and cell type heterogeneity. The discovery set contained 689 SZ cases and 645 controls (n = 1334), from 3 multisite consortia: the Consortium on the Genetics of Endophenotypes in Schizophrenia, the Project among African-Americans To Explore Risks for Schizophrenia, and the Multiplex Multigenerational Family Study of Schizophrenia. The replication set contained 247 SZ cases and 250 controls (n = 497) from the Genomic Psychiatry Cohort. Main Outcomes and Measures: Identification of differentially methylated positions across the genome in SZ cases compared with controls. RESULTS Of the 689 case participants in the discovery set, 477 (69{\%}) were men and 258 (37{\%}) were non-African American; of the 645 controls, 273 (42{\%}) were men and 419 (65{\%}) were non-African American. In our replication set, cases/controls were 76{\%}male and 100{\%} non-African American.We identified SZ-associated methylation differences at 923 CpGs in the discovery set (false discovery rate,",
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AU - Trygvadottir, Rakel

AU - Idrizi, Adrian

AU - Runarsson, Arni

AU - Berndsen, Birna

AU - Gur, Ruben C.

AU - Moore, Tyler M.

AU - Perry, Rodney T.

AU - Fugman, Doug

AU - Sabunciyan, Sarven

AU - Yolken, Robert H

AU - Hyde, Thomas

AU - Kleinman, Joel

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AU - Pato, Michele T.

AU - Go, Rodney C.

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N2 - Importance: DNA methylation may play an important role in schizophrenia (SZ), either directly as a mechanism of pathogenesis or as a biomarker of risk. O. Objective: To scan genome-wide DNA methylation data to identify differentially methylated CpGs between SZ cases and controls. Design, Setting, and Participants: Epigenome-wide association study begun in 2008 using DNA methylation levels of 456 513 CpG loci measured on the Infinium HumanMethylation450 array (Illumina) in a consortium of case-control studies for initial discovery and in an independent replication set. Primary analyses used general linear regression, adjusting for age, sex, race/ethnicity, smoking, batch, and cell type heterogeneity. The discovery set contained 689 SZ cases and 645 controls (n = 1334), from 3 multisite consortia: the Consortium on the Genetics of Endophenotypes in Schizophrenia, the Project among African-Americans To Explore Risks for Schizophrenia, and the Multiplex Multigenerational Family Study of Schizophrenia. The replication set contained 247 SZ cases and 250 controls (n = 497) from the Genomic Psychiatry Cohort. Main Outcomes and Measures: Identification of differentially methylated positions across the genome in SZ cases compared with controls. RESULTS Of the 689 case participants in the discovery set, 477 (69%) were men and 258 (37%) were non-African American; of the 645 controls, 273 (42%) were men and 419 (65%) were non-African American. In our replication set, cases/controls were 76%male and 100% non-African American.We identified SZ-associated methylation differences at 923 CpGs in the discovery set (false discovery rate,

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