2024-03-29T11:43:09Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00013030
2023-01-16T03:59:59Z
499:960:1165
Resequencing and Association Analysis of the KALRN and EPHB1 Genes And Their Contribution to Schizophrenia Susceptibility
Kushima, Itaru
40992
Nakamura, Yukako
40993
Aleksic, Branko
40994
Ikeda, Masashi
40995
Ito, Yoshihito
40996
Shiino, Tomoko
40997
Okochi, Tomo
40998
Fukuo, Yasuhisa
40999
Ujike, Hiroshi
41000
Suzuki, Michio
41001
Inada, Toshiya
41002
Hashimoto, Ryota
41003
Takeda, Masatoshi
41004
Kaibuchi, Kozo
41005
Iwata, Nakao
41006
Ozaki, Norio
41007
synaptogenic pathway
rare missense mutations
GWAS
Japanese population
名古屋大学
NAGOYA University
博士(医学)
Background: Our genome-wide association study of schizophrenia found association signals at the Kalirin gene (KALRN) and EPH receptor B1 gene (EPHB1) in a Japanese population. The importance of these synaptogenic pathway genes in schizophrenia is gaining independent supports. Although there has been growing interest in rare (<1%) missense mutations as potential contributors to the unexplained heritability of schizophrenia, there are no population-based studies targeting rare (<1%) coding mutations with a larger effect size (eg, OR >1.5) in KALRN or EPHB1. Methods and Results: The present study design consisted of 3 phases. At the discovery phase, we conducted resequencing analyses for all exon regions of KALRN and EPHB1 using a DNA microarray–based method. Seventeen rare (<1%) missense mutations were discovered in the first sample set (320 schizophrenic patients). After the prioritization phase based on frequencies in the second sample set (729 cases and 562 controls), we performed association analyses for each selected mutation using the third sample set (1511 cases and 1517 controls), along with a combined association analysis across all selected mutations. In KALRN, we detected a significant association between schizophrenia and P2255T (OR 5 2.09, corrected P = .048, 1 tailed); this was supported in the combined association analysis (OR52.07, corrected P = .006, 1 tailed). We found no evidence of association of EPHB1 with schizophrenia. In silico analysis indicated the functional relevance of these rare missense mutations. Conclusion: We provide evidence that multiple rare (<1%) missense mutations in KALRN may be genetic risk factors for schizophrenia.
名古屋大学博士学位論文 学位の種類 : 博士(医学)(課程) 学位授与年月日:平成23年3月25日 久島周氏の博士論文として提出された
First published online: November 1, 2010
doctoral thesis
Oxford University Press
2012-03
application/pdf
Schizophrenia Bulletin
3
38
552
560
甲第9061号
http://dx.doi.org/10.1093/schbul/sbq118
http://hdl.handle.net/2237/14925
1745-1701
https://nagoya.repo.nii.ac.jp/record/13030/files/k9061.pdf
eng
https://doi.org/10.1093/schbul/sbq118
© The Author 2010. Published by Oxford University Press.