The impact of the genome-wide supported variant in the cyclin M2 gene on gray matter morphology in schizophrenia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-10-25

AUTHORS

Kazutaka Ohi, Ryota Hashimoto, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Satomi Umeda-Yano, Masaki Fukunaga, Yoshiyuki Watanabe, Masao Iwase, Hiroaki Kazui, Masatoshi Takeda

ABSTRACT

BackgroundGenome-wide significant associations of schizophrenia with eight SNPs in the CNNM2, MIR137, PCGEM1, TRIM26, CSMD1, MMP16, NT5C2 and CCDC68 genes have been identified in a recent mega-analysis of genome-wide association studies. To date, the role of these SNPs on gray matter (GM) volumes remains unclear.MethodsAfter performing quality control for minor-allele frequency > 5% using a JPT HapMap sample and our sample, a genotyping call rate > 95% and Hardy-Weinberg equilibrium testing (p > 0.01), five of eight SNPs were eligible for analysis. We used a comprehensive voxel-based morphometry (VBM) technique to investigate the effects of these five SNPs on GM volumes between major-allele homozygotes and minor-allele carriers in Japanese patients with schizophrenia (n = 173) and healthy subjects (n = 449).ResultsThe rs7914558 risk variant at CNNM2 was associated with voxel-based GM volumes in the bilateral inferior frontal gyri (right T = 4.96, p = 0.0088, left T = 4.66, p = 0.031). These peak voxels, which were affected by the variant, existed in the orbital region of the inferior frontal gyri. Individuals with the risk G/G genotype of rs7914558 had smaller GM volumes in the bilateral inferior frontal gyri than carriers of the non-risk A-allele. Although several effects of the genotype and the genotype-diagnosis interaction of other SNPs on GM volumes were observed in the exploratory VBM analyses, these effects did not remain after the FWE- correction for multiple tests (p > 0.05).ConclusionsOur findings suggest that the genetic variant in the CNNM2 gene could be implicated in the pathogenesis of schizophrenia through the GM volumetric vulnerability of the orbital regions in the inferior frontal gyri. More... »

PAGES

40

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1744-9081-9-40

DOI

http://dx.doi.org/10.1186/1744-9081-9-40

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1040116845

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24160291


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35 schema:description BackgroundGenome-wide significant associations of schizophrenia with eight SNPs in the CNNM2, MIR137, PCGEM1, TRIM26, CSMD1, MMP16, NT5C2 and CCDC68 genes have been identified in a recent mega-analysis of genome-wide association studies. To date, the role of these SNPs on gray matter (GM) volumes remains unclear.MethodsAfter performing quality control for minor-allele frequency > 5% using a JPT HapMap sample and our sample, a genotyping call rate > 95% and Hardy-Weinberg equilibrium testing (p > 0.01), five of eight SNPs were eligible for analysis. We used a comprehensive voxel-based morphometry (VBM) technique to investigate the effects of these five SNPs on GM volumes between major-allele homozygotes and minor-allele carriers in Japanese patients with schizophrenia (n = 173) and healthy subjects (n = 449).ResultsThe rs7914558 risk variant at CNNM2 was associated with voxel-based GM volumes in the bilateral inferior frontal gyri (right T = 4.96, p = 0.0088, left T = 4.66, p = 0.031). These peak voxels, which were affected by the variant, existed in the orbital region of the inferior frontal gyri. Individuals with the risk G/G genotype of rs7914558 had smaller GM volumes in the bilateral inferior frontal gyri than carriers of the non-risk A-allele. Although several effects of the genotype and the genotype-diagnosis interaction of other SNPs on GM volumes were observed in the exploratory VBM analyses, these effects did not remain after the FWE- correction for multiple tests (p > 0.05).ConclusionsOur findings suggest that the genetic variant in the CNNM2 gene could be implicated in the pathogenesis of schizophrenia through the GM volumetric vulnerability of the orbital regions in the inferior frontal gyri.
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41 schema:keywords A allele
42 CNNM2
43 CNNM2 gene
44 CSMD1
45 ConclusionsOur findings
46 G genotype
47 GM volume
48 HapMap samples
49 Japanese patients
50 M2 gene
51 MIR137
52 MMP16
53 MethodsAfter
54 NT5C2
55 PCGEM1
56 SNPs
57 TRIM26
58 VBM analysis
59 Weinberg equilibrium testing
60 analysis
61 association
62 association studies
63 bilateral inferior frontal gyrus
64 call rate
65 carriers
66 control
67 date
68 effect
69 equilibrium testing
70 findings
71 frequency
72 frontal gyrus
73 genes
74 genetic variants
75 genome
76 genome-wide association studies
77 genotype-diagnosis interaction
78 genotypes
79 gray matter morphology
80 gray matter volume
81 gyrus
82 healthy subjects
83 homozygotes
84 impact
85 individuals
86 inferior frontal gyrus
87 interaction
88 major allele homozygotes
89 matter volume
90 minor allele carriers
91 minor allele frequency
92 morphology
93 morphometry technique
94 multiple tests
95 orbital region
96 pathogenesis
97 pathogenesis of schizophrenia
98 patients
99 peak voxels
100 quality control
101 rate
102 region
103 risk variants
104 role
105 samples
106 schizophrenia
107 significant association
108 smaller GM volume
109 study
110 subjects
111 technique
112 test
113 testing
114 variants
115 volume
116 voxel-based morphometry technique
117 voxels
118 vulnerability
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