Common genetic variants have associations with human cortical brain regions and risk of schizophrenia

Xuan Bi; Long Feng; Shiying Wang; Zijie Lin; Tengfei Li; Bingxin Zhao; Hongtu Zhu; Heping Zhang

doi:10.1002/gepi.22203

Common genetic variants have associations with human cortical brain regions and risk of schizophrenia

Xuan Bi, Long Feng, Shiying Wang, Zijie Lin, Tengfei Li, Bingxin Zhao, Hongtu Zhu, Heping Zhang

Information and Decision Sciences

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1 Scopus citations

Abstract

Schizophrenia is a highly heritable mental disorder and is reported to be associated with measurements in cortical regions of the human brain. In this study, we considered genome-wide association studies to uncover genetic effects on cortical regions and prodromal symptoms of schizophrenia. Specifically, area, thickness, and volume of 66 cortical regions derived from magnetic resonance imaging scans of 1,445 children and adolescents from the Philadelphia Neurodevelopmental Cohort were studied. Two common variants were identified as being associated with two prefrontal cortical regions (one significant variant rs11601331 on chromosome 11p11 for right rostral middle frontal gyral area, p = 1.97 × 10 ⁻⁸; one suggestive variant rs2345981 on chromosome 6q11 for left frontal pole gyral volume, p = 2.07 × 10 ⁻⁷), where the significance of rs11601331 was independently replicated on the Pediatric Imaging, Neurocognition, and Genetics study of size 1,239 (p = 9.19 × 10 ⁻³). Moreover, genetic effects on schizophrenia were investigated based on a sample of 8,719 subjects. The two identified variants rs11601331 and rs2345981 showed significant association with the longest prodromal symptoms duration (p = 0.048 and p = 0.027, respectively).

Original language	English (US)
Pages (from-to)	548-558
Number of pages	11
Journal	Genetic epidemiology
Volume	43
Issue number	5
DOIs	https://doi.org/10.1002/gepi.22203
State	Published - Jul 2019

Bibliographical note

Funding Information:
National Science Foundation, Grant/ Award Numbers: DMS‐1722544, DMS‐1407655, SES‐1357666; National Institute on Drug Abuse, Grant/Award Numbers: DA029475, DA016750; National Institute of Mental Health, Grant/Award Numbers: MH086633, MH089924, MH116527; NIH, Grant/Award Number: RC2MH089983; NSF; Cancer Prevention Research Institute of Texas, Grant/Award Number: RR150054; Eunice Kennedy Shriver National Institute of Child Health & Human Development, Grant/Award Number: RC2DA029475

Funding Information:
This research was partially supported by grant R01 DA016750 from National Institute on Drug Abuse; NIH grants R01 MH116527 and MH086633; NSF grants SES‐ 1357666, DMS‐1722544, and DMS‐1407655; Cancer Prevention Research Institute of Texas grant RR150054, and the endowed Bao‐Shan Jing Professorship in Diagnostic Imaging. We thank the two anonymous referees whose comments and suggestions improved the manuscript significantly. Support for the collection of the PNC data sets was provided by NIH grant RC2MH089983 awarded to Raquel Gur and RC2MH089924 awarded to Hakon Hakonarson. All PNC participants were recruited through the Center for Applied Genomics at The Children’s Hospital in Philadelphia. The PNC data sets used in this manuscript were obtained from dbGaP at https://www.ncbi.nlm.nih.gov/projects/gap/cgi‐bin/ study.cgi?study_id=phs000607.v1.p1 through dbGaP accession: phs000607.v1.p1. Data collection and sharing for this project was funded by the Pediatric Imaging, Neurocognition and Genetics Study (PING) (National Institutes of Health Grant RC2DA029475). PING is funded by the National Institute on Drug Abuse and the Eunice Kennedy Shriver National Institute of Child Health & Human Development. PING data are disseminated by the PING Coordinating Center at the Center for Human Development, University of California, San Diego. The key investigators of PING include Hauke Bartsch, Anders M. Dale, Anthony Gamst, Connor McCabe, Erik Newman, Joshua Kuperman, Mark Appel-baum, NatachaAkshoomooff, Terry L. Jernigan, Wesley Thompson, Peter Van Zijl, Stewart Mostofsky, Walter Kaufmann, Bruce Rosen, Tal Kenet, Alisa Powers, B.J. Casey, Erika J. Ruberry, Nicholas J. Schork, Cinnamon Bloss, Sarah Murray, David Amaral, Elizabeth Sowell, Brian Keating, Linda Chang, Thomas Ernst, David Kennedy, Jean Frazier, and Jeffrey R. Gruen.

Funding Information:
This research was partially supported by grant R01 DA016750 from National Institute on Drug Abuse; NIH grants R01 MH116527 and MH086633; NSF grants SES-1357666, DMS-1722544, and DMS-1407655; Cancer Prevention Research Institute of Texas grant RR150054, and the endowed Bao-Shan Jing Professorship in Diagnostic Imaging. We thank the two anonymous referees whose comments and suggestions improved the manuscript significantly. Support for the collection of the PNC data sets was provided by NIH grant RC2MH089983 awarded to Raquel Gur and RC2MH089924 awarded to Hakon Hakonarson. All PNC participants were recruited through the Center for Applied Genomics at The Children's Hospital in Philadelphia. The PNC data sets used in this manuscript were obtained from dbGaP at https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000607.v1.p1 through dbGaP accession: phs000607.v1.p1. Data collection and sharing for this project was funded by the Pediatric Imaging, Neurocognition and Genetics Study (PING) (National Institutes of Health Grant RC2DA029475). PING is funded by the National Institute on Drug Abuse and the Eunice Kennedy Shriver National Institute of Child Health & Human Development. PING data are disseminated by the PING Coordinating Center at the Center for Human Development, University of California, San Diego. The key investigators of PING include Hauke Bartsch, Anders M. Dale, Anthony Gamst, Connor McCabe, Erik Newman, Joshua Kuperman, Mark Appelbaum, NatachaAkshoomooff, Terry L. Jernigan, Wesley Thompson, Peter Van Zijl, Stewart Mostofsky, Walter Kaufmann, Bruce Rosen, Tal Kenet, Alisa Powers, B.J. Casey, Erika J. Ruberry, Nicholas J. Schork, Cinnamon Bloss, Sarah Murray, David Amaral, Elizabeth Sowell, Brian Keating, Linda Chang, Thomas Ernst, David Kennedy, Jean Frazier, and Jeffrey R. Gruen.

Publisher Copyright:
© 2019 Wiley Periodicals, Inc.

Keywords

cortical regions
genome-wide association studies
imaging traits
intermediate phenotypes
schizophrenia

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10.1002/gepi.22203

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@article{bf604a13d6b5487ea05c84fd9924646c,

title = "Common genetic variants have associations with human cortical brain regions and risk of schizophrenia",

abstract = "Schizophrenia is a highly heritable mental disorder and is reported to be associated with measurements in cortical regions of the human brain. In this study, we considered genome-wide association studies to uncover genetic effects on cortical regions and prodromal symptoms of schizophrenia. Specifically, area, thickness, and volume of 66 cortical regions derived from magnetic resonance imaging scans of 1,445 children and adolescents from the Philadelphia Neurodevelopmental Cohort were studied. Two common variants were identified as being associated with two prefrontal cortical regions (one significant variant rs11601331 on chromosome 11p11 for right rostral middle frontal gyral area, p = 1.97 × 10 −8; one suggestive variant rs2345981 on chromosome 6q11 for left frontal pole gyral volume, p = 2.07 × 10 −7), where the significance of rs11601331 was independently replicated on the Pediatric Imaging, Neurocognition, and Genetics study of size 1,239 (p = 9.19 × 10 −3). Moreover, genetic effects on schizophrenia were investigated based on a sample of 8,719 subjects. The two identified variants rs11601331 and rs2345981 showed significant association with the longest prodromal symptoms duration (p = 0.048 and p = 0.027, respectively).",

keywords = "cortical regions, genome-wide association studies, imaging traits, intermediate phenotypes, schizophrenia",

author = "Xuan Bi and Long Feng and Shiying Wang and Zijie Lin and Tengfei Li and Bingxin Zhao and Hongtu Zhu and Heping Zhang",

note = "Funding Information: National Science Foundation, Grant/ Award Numbers: DMS‐1722544, DMS‐1407655, SES‐1357666; National Institute on Drug Abuse, Grant/Award Numbers: DA029475, DA016750; National Institute of Mental Health, Grant/Award Numbers: MH086633, MH089924, MH116527; NIH, Grant/Award Number: RC2MH089983; NSF; Cancer Prevention Research Institute of Texas, Grant/Award Number: RR150054; Eunice Kennedy Shriver National Institute of Child Health & Human Development, Grant/Award Number: RC2DA029475 Funding Information: This research was partially supported by grant R01 DA016750 from National Institute on Drug Abuse; NIH grants R01 MH116527 and MH086633; NSF grants SES‐ 1357666, DMS‐1722544, and DMS‐1407655; Cancer Prevention Research Institute of Texas grant RR150054, and the endowed Bao‐Shan Jing Professorship in Diagnostic Imaging. We thank the two anonymous referees whose comments and suggestions improved the manuscript significantly. Support for the collection of the PNC data sets was provided by NIH grant RC2MH089983 awarded to Raquel Gur and RC2MH089924 awarded to Hakon Hakonarson. All PNC participants were recruited through the Center for Applied Genomics at The Children{\textquoteright}s Hospital in Philadelphia. The PNC data sets used in this manuscript were obtained from dbGaP at https://www.ncbi.nlm.nih.gov/projects/gap/cgi‐bin/ study.cgi?study_id=phs000607.v1.p1 through dbGaP accession: phs000607.v1.p1. Data collection and sharing for this project was funded by the Pediatric Imaging, Neurocognition and Genetics Study (PING) (National Institutes of Health Grant RC2DA029475). PING is funded by the National Institute on Drug Abuse and the Eunice Kennedy Shriver National Institute of Child Health & Human Development. PING data are disseminated by the PING Coordinating Center at the Center for Human Development, University of California, San Diego. The key investigators of PING include Hauke Bartsch, Anders M. Dale, Anthony Gamst, Connor McCabe, Erik Newman, Joshua Kuperman, Mark Appel-baum, NatachaAkshoomooff, Terry L. Jernigan, Wesley Thompson, Peter Van Zijl, Stewart Mostofsky, Walter Kaufmann, Bruce Rosen, Tal Kenet, Alisa Powers, B.J. Casey, Erika J. Ruberry, Nicholas J. Schork, Cinnamon Bloss, Sarah Murray, David Amaral, Elizabeth Sowell, Brian Keating, Linda Chang, Thomas Ernst, David Kennedy, Jean Frazier, and Jeffrey R. Gruen. Funding Information: This research was partially supported by grant R01 DA016750 from National Institute on Drug Abuse; NIH grants R01 MH116527 and MH086633; NSF grants SES-1357666, DMS-1722544, and DMS-1407655; Cancer Prevention Research Institute of Texas grant RR150054, and the endowed Bao-Shan Jing Professorship in Diagnostic Imaging. We thank the two anonymous referees whose comments and suggestions improved the manuscript significantly. Support for the collection of the PNC data sets was provided by NIH grant RC2MH089983 awarded to Raquel Gur and RC2MH089924 awarded to Hakon Hakonarson. All PNC participants were recruited through the Center for Applied Genomics at The Children's Hospital in Philadelphia. The PNC data sets used in this manuscript were obtained from dbGaP at https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000607.v1.p1 through dbGaP accession: phs000607.v1.p1. Data collection and sharing for this project was funded by the Pediatric Imaging, Neurocognition and Genetics Study (PING) (National Institutes of Health Grant RC2DA029475). PING is funded by the National Institute on Drug Abuse and the Eunice Kennedy Shriver National Institute of Child Health & Human Development. PING data are disseminated by the PING Coordinating Center at the Center for Human Development, University of California, San Diego. The key investigators of PING include Hauke Bartsch, Anders M. Dale, Anthony Gamst, Connor McCabe, Erik Newman, Joshua Kuperman, Mark Appelbaum, NatachaAkshoomooff, Terry L. Jernigan, Wesley Thompson, Peter Van Zijl, Stewart Mostofsky, Walter Kaufmann, Bruce Rosen, Tal Kenet, Alisa Powers, B.J. Casey, Erika J. Ruberry, Nicholas J. Schork, Cinnamon Bloss, Sarah Murray, David Amaral, Elizabeth Sowell, Brian Keating, Linda Chang, Thomas Ernst, David Kennedy, Jean Frazier, and Jeffrey R. Gruen. Publisher Copyright: {\textcopyright} 2019 Wiley Periodicals, Inc.",

year = "2019",

month = jul,

doi = "10.1002/gepi.22203",

language = "English (US)",

volume = "43",

pages = "548--558",

journal = "Genetic epidemiology",

issn = "0741-0395",

publisher = "Wiley-Liss Inc.",

number = "5",

}

TY - JOUR

T1 - Common genetic variants have associations with human cortical brain regions and risk of schizophrenia

AU - Bi, Xuan

AU - Feng, Long

AU - Wang, Shiying

AU - Lin, Zijie

AU - Li, Tengfei

AU - Zhao, Bingxin

AU - Zhu, Hongtu

AU - Zhang, Heping

N1 - Funding Information: National Science Foundation, Grant/ Award Numbers: DMS‐1722544, DMS‐1407655, SES‐1357666; National Institute on Drug Abuse, Grant/Award Numbers: DA029475, DA016750; National Institute of Mental Health, Grant/Award Numbers: MH086633, MH089924, MH116527; NIH, Grant/Award Number: RC2MH089983; NSF; Cancer Prevention Research Institute of Texas, Grant/Award Number: RR150054; Eunice Kennedy Shriver National Institute of Child Health & Human Development, Grant/Award Number: RC2DA029475 Funding Information: This research was partially supported by grant R01 DA016750 from National Institute on Drug Abuse; NIH grants R01 MH116527 and MH086633; NSF grants SES‐ 1357666, DMS‐1722544, and DMS‐1407655; Cancer Prevention Research Institute of Texas grant RR150054, and the endowed Bao‐Shan Jing Professorship in Diagnostic Imaging. We thank the two anonymous referees whose comments and suggestions improved the manuscript significantly. Support for the collection of the PNC data sets was provided by NIH grant RC2MH089983 awarded to Raquel Gur and RC2MH089924 awarded to Hakon Hakonarson. All PNC participants were recruited through the Center for Applied Genomics at The Children’s Hospital in Philadelphia. The PNC data sets used in this manuscript were obtained from dbGaP at https://www.ncbi.nlm.nih.gov/projects/gap/cgi‐bin/ study.cgi?study_id=phs000607.v1.p1 through dbGaP accession: phs000607.v1.p1. Data collection and sharing for this project was funded by the Pediatric Imaging, Neurocognition and Genetics Study (PING) (National Institutes of Health Grant RC2DA029475). PING is funded by the National Institute on Drug Abuse and the Eunice Kennedy Shriver National Institute of Child Health & Human Development. PING data are disseminated by the PING Coordinating Center at the Center for Human Development, University of California, San Diego. The key investigators of PING include Hauke Bartsch, Anders M. Dale, Anthony Gamst, Connor McCabe, Erik Newman, Joshua Kuperman, Mark Appel-baum, NatachaAkshoomooff, Terry L. Jernigan, Wesley Thompson, Peter Van Zijl, Stewart Mostofsky, Walter Kaufmann, Bruce Rosen, Tal Kenet, Alisa Powers, B.J. Casey, Erika J. Ruberry, Nicholas J. Schork, Cinnamon Bloss, Sarah Murray, David Amaral, Elizabeth Sowell, Brian Keating, Linda Chang, Thomas Ernst, David Kennedy, Jean Frazier, and Jeffrey R. Gruen. Funding Information: This research was partially supported by grant R01 DA016750 from National Institute on Drug Abuse; NIH grants R01 MH116527 and MH086633; NSF grants SES-1357666, DMS-1722544, and DMS-1407655; Cancer Prevention Research Institute of Texas grant RR150054, and the endowed Bao-Shan Jing Professorship in Diagnostic Imaging. We thank the two anonymous referees whose comments and suggestions improved the manuscript significantly. Support for the collection of the PNC data sets was provided by NIH grant RC2MH089983 awarded to Raquel Gur and RC2MH089924 awarded to Hakon Hakonarson. All PNC participants were recruited through the Center for Applied Genomics at The Children's Hospital in Philadelphia. The PNC data sets used in this manuscript were obtained from dbGaP at https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000607.v1.p1 through dbGaP accession: phs000607.v1.p1. Data collection and sharing for this project was funded by the Pediatric Imaging, Neurocognition and Genetics Study (PING) (National Institutes of Health Grant RC2DA029475). PING is funded by the National Institute on Drug Abuse and the Eunice Kennedy Shriver National Institute of Child Health & Human Development. PING data are disseminated by the PING Coordinating Center at the Center for Human Development, University of California, San Diego. The key investigators of PING include Hauke Bartsch, Anders M. Dale, Anthony Gamst, Connor McCabe, Erik Newman, Joshua Kuperman, Mark Appelbaum, NatachaAkshoomooff, Terry L. Jernigan, Wesley Thompson, Peter Van Zijl, Stewart Mostofsky, Walter Kaufmann, Bruce Rosen, Tal Kenet, Alisa Powers, B.J. Casey, Erika J. Ruberry, Nicholas J. Schork, Cinnamon Bloss, Sarah Murray, David Amaral, Elizabeth Sowell, Brian Keating, Linda Chang, Thomas Ernst, David Kennedy, Jean Frazier, and Jeffrey R. Gruen. Publisher Copyright: © 2019 Wiley Periodicals, Inc.

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Y1 - 2019/7

N2 - Schizophrenia is a highly heritable mental disorder and is reported to be associated with measurements in cortical regions of the human brain. In this study, we considered genome-wide association studies to uncover genetic effects on cortical regions and prodromal symptoms of schizophrenia. Specifically, area, thickness, and volume of 66 cortical regions derived from magnetic resonance imaging scans of 1,445 children and adolescents from the Philadelphia Neurodevelopmental Cohort were studied. Two common variants were identified as being associated with two prefrontal cortical regions (one significant variant rs11601331 on chromosome 11p11 for right rostral middle frontal gyral area, p = 1.97 × 10 −8; one suggestive variant rs2345981 on chromosome 6q11 for left frontal pole gyral volume, p = 2.07 × 10 −7), where the significance of rs11601331 was independently replicated on the Pediatric Imaging, Neurocognition, and Genetics study of size 1,239 (p = 9.19 × 10 −3). Moreover, genetic effects on schizophrenia were investigated based on a sample of 8,719 subjects. The two identified variants rs11601331 and rs2345981 showed significant association with the longest prodromal symptoms duration (p = 0.048 and p = 0.027, respectively).

AB - Schizophrenia is a highly heritable mental disorder and is reported to be associated with measurements in cortical regions of the human brain. In this study, we considered genome-wide association studies to uncover genetic effects on cortical regions and prodromal symptoms of schizophrenia. Specifically, area, thickness, and volume of 66 cortical regions derived from magnetic resonance imaging scans of 1,445 children and adolescents from the Philadelphia Neurodevelopmental Cohort were studied. Two common variants were identified as being associated with two prefrontal cortical regions (one significant variant rs11601331 on chromosome 11p11 for right rostral middle frontal gyral area, p = 1.97 × 10 −8; one suggestive variant rs2345981 on chromosome 6q11 for left frontal pole gyral volume, p = 2.07 × 10 −7), where the significance of rs11601331 was independently replicated on the Pediatric Imaging, Neurocognition, and Genetics study of size 1,239 (p = 9.19 × 10 −3). Moreover, genetic effects on schizophrenia were investigated based on a sample of 8,719 subjects. The two identified variants rs11601331 and rs2345981 showed significant association with the longest prodromal symptoms duration (p = 0.048 and p = 0.027, respectively).

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KW - genome-wide association studies

KW - imaging traits

KW - intermediate phenotypes

KW - schizophrenia

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Common genetic variants have associations with human cortical brain regions and risk of schizophrenia

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