An association screen of myelin-related genes implicates the chromosome 22q11 PIK4CA gene in schizophrenia

B. J. Jungerius; M. L. C. Hoogendoorn; S. C. Bakker; R. van't Slot; A. F. Bardoel; R. A. Ophoff; C. Wijmenga; R. S. Kahn; R. J. Sinke

doi:10.1038/sj.mp.4002080

An association screen of myelin-related genes implicates the chromosome 22q11 PIK4CA gene in schizophrenia

B. J. Jungerius, M. L. C. Hoogendoorn, S. C. Bakker, R. van't Slot, A. F. Bardoel, R. A. Ophoff, C. Wijmenga, R. S. Kahn, R. J. Sinke^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Several lines of evidence, including expression analyses, brain imaging and genetic studies suggest that the integrity of myelin is disturbed in schizophrenia patients. In this study, we first reconstructed a pathway of 138 myelin-related genes, all involved in myelin structure, composition, development or maintenance. Then we performed a two-stage association analysis on these 138 genes using 771 single nucleotide polymorphisms (SNPs). Analysis of our data from 310 cases vs 880 controls demonstrated association of 10 SNPs from six genes. Specifically, we observed highly significant P-values for association in PIK4CA (observed P = 6.1 x 10(-6)). These findings remained significant after Bonferroni correction for 771 tests. The PIK4CA gene is located in the chromosome 22q11 deletion syndrome region, which is of particular interest because it has been implicated in schizophrenia. We also report weak association of SNPs in PIK3C2G, FGF1, FGFR1, ARHGEF10 and PSAP (observed P

Original language	English
Pages (from-to)	1060-1068
Number of pages	9
Journal	Molecular Psychiatry
Volume	13
Issue number	11
DOIs	https://doi.org/10.1038/sj.mp.4002080
Publication status	Published - Nov-2008

Keywords

schizophrenia
myelin
white matter
oligodendrocyte
22q11
PIK4CA
GENOME-WIDE SCAN
II PHOSPHOINOSITIDE 3-KINASE
ASHKENAZI JEWISH FAMILIES
SUSCEPTIBILITY LOCI
PREFRONTAL CORTEX
BIPOLAR-DISORDER
PROMOTER REGION
PSYCHIATRIC-DISORDERS
CONVERGENT EVIDENCE
NEGATIVE-SYMPTOMS

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title = "An association screen of myelin-related genes implicates the chromosome 22q11 PIK4CA gene in schizophrenia",

abstract = "Several lines of evidence, including expression analyses, brain imaging and genetic studies suggest that the integrity of myelin is disturbed in schizophrenia patients. In this study, we first reconstructed a pathway of 138 myelin-related genes, all involved in myelin structure, composition, development or maintenance. Then we performed a two-stage association analysis on these 138 genes using 771 single nucleotide polymorphisms (SNPs). Analysis of our data from 310 cases vs 880 controls demonstrated association of 10 SNPs from six genes. Specifically, we observed highly significant P-values for association in PIK4CA (observed P = 6.1 x 10(-6)). These findings remained significant after Bonferroni correction for 771 tests. The PIK4CA gene is located in the chromosome 22q11 deletion syndrome region, which is of particular interest because it has been implicated in schizophrenia. We also report weak association of SNPs in PIK3C2G, FGF1, FGFR1, ARHGEF10 and PSAP (observed P",

keywords = "schizophrenia, myelin, white matter, oligodendrocyte, 22q11, PIK4CA, GENOME-WIDE SCAN, II PHOSPHOINOSITIDE 3-KINASE, ASHKENAZI JEWISH FAMILIES, SUSCEPTIBILITY LOCI, PREFRONTAL CORTEX, BIPOLAR-DISORDER, PROMOTER REGION, PSYCHIATRIC-DISORDERS, CONVERGENT EVIDENCE, NEGATIVE-SYMPTOMS",

author = "Jungerius, {B. J.} and Hoogendoorn, {M. L. C.} and Bakker, {S. C.} and {van't Slot}, R. and Bardoel, {A. F.} and Ophoff, {R. A.} and C. Wijmenga and Kahn, {R. S.} and Sinke, {R. J.}",

year = "2008",

month = nov,

doi = "10.1038/sj.mp.4002080",

language = "English",

volume = "13",

pages = "1060--1068",

journal = "Molecular Psychiatry",

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AU - Jungerius, B. J.

AU - Hoogendoorn, M. L. C.

AU - Bakker, S. C.

AU - van't Slot, R.

AU - Bardoel, A. F.

AU - Ophoff, R. A.

AU - Wijmenga, C.

AU - Kahn, R. S.

AU - Sinke, R. J.

PY - 2008/11

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N2 - Several lines of evidence, including expression analyses, brain imaging and genetic studies suggest that the integrity of myelin is disturbed in schizophrenia patients. In this study, we first reconstructed a pathway of 138 myelin-related genes, all involved in myelin structure, composition, development or maintenance. Then we performed a two-stage association analysis on these 138 genes using 771 single nucleotide polymorphisms (SNPs). Analysis of our data from 310 cases vs 880 controls demonstrated association of 10 SNPs from six genes. Specifically, we observed highly significant P-values for association in PIK4CA (observed P = 6.1 x 10(-6)). These findings remained significant after Bonferroni correction for 771 tests. The PIK4CA gene is located in the chromosome 22q11 deletion syndrome region, which is of particular interest because it has been implicated in schizophrenia. We also report weak association of SNPs in PIK3C2G, FGF1, FGFR1, ARHGEF10 and PSAP (observed P

AB - Several lines of evidence, including expression analyses, brain imaging and genetic studies suggest that the integrity of myelin is disturbed in schizophrenia patients. In this study, we first reconstructed a pathway of 138 myelin-related genes, all involved in myelin structure, composition, development or maintenance. Then we performed a two-stage association analysis on these 138 genes using 771 single nucleotide polymorphisms (SNPs). Analysis of our data from 310 cases vs 880 controls demonstrated association of 10 SNPs from six genes. Specifically, we observed highly significant P-values for association in PIK4CA (observed P = 6.1 x 10(-6)). These findings remained significant after Bonferroni correction for 771 tests. The PIK4CA gene is located in the chromosome 22q11 deletion syndrome region, which is of particular interest because it has been implicated in schizophrenia. We also report weak association of SNPs in PIK3C2G, FGF1, FGFR1, ARHGEF10 and PSAP (observed P

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KW - white matter

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KW - ASHKENAZI JEWISH FAMILIES

KW - SUSCEPTIBILITY LOCI

KW - PREFRONTAL CORTEX

KW - BIPOLAR-DISORDER

KW - PROMOTER REGION

KW - PSYCHIATRIC-DISORDERS

KW - CONVERGENT EVIDENCE

KW - NEGATIVE-SYMPTOMS

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DO - 10.1038/sj.mp.4002080

M3 - Article

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JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 11

ER -

An association screen of myelin-related genes implicates the chromosome 22q11 PIK4CA gene in schizophrenia

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