Abstract
Rare genomic variations inherited in multiplex schizophrenia families are suggested to play a role in the genetic etiology of the disease. To identify rare variations with large effects on the risk of developing schizophrenia, we performed whole-exome sequencing (WES) in two affected and one unaffected individual of a multiplex family with 10 affected individuals. We also performed follow-up resequencing of the unc-13 homolog B (Caenorhabditis elegans) (UNC13B) gene, a potential risk gene identified by WES, in the multiplex family and undertook a case–control study to investigate association between UNC13B and schizophrenia. UNC13B coding regions (39 exons) from 15 individuals of the multiplex family and 111 affected offspring for whom parental DNA samples were available were resequenced. Rare missense UNC13B variations identified by resequencing were further tested for association with schizophrenia in two independent case–control populations comprising a total of 1,753 patients and 1,602 controls. A rare missense variation (V1525M) in UNC13B was identified by WES in the multiplex family; this variation was present in five of six affected individuals, but not in eight unaffected individuals or one individual of unknown disease status. Resequencing UNC13B coding regions identified five rare missense variations (T103M, M813T, P1349T, I1362T, and V1525M). In the case–control study, there was no significant association between rare missense UNC13B variations and schizophrenia, although single-variant meta-analysis indicated that M813T was nominally associated with schizophrenia. These results do not support a contribution of rare missense UNC13B variations to the genetic etiology of schizophrenia in the Japanese population.
| Original language | English |
|---|---|
| Pages (from-to) | 797-805 |
| Number of pages | 9 |
| Journal | American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics |
| Volume | 171 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 01-09-2016 |
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All Science Journal Classification (ASJC) codes
- Genetics(clinical)
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
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Rare UNC13B variations and risk of schizophrenia : Whole-exome sequencing in a multiplex family and follow-up resequencing and a case–control study. / Egawa, Jun; Hoya, Satoshi; Watanabe, Yuichiro; Nunokawa, Ayako; Shibuya, Masako; Ikeda, Masashi; Inoue, Emiko; Okuda, Shujiro; Kondo, Kenji; Saito, Takeo; Kaneko, Naoshi; Muratake, Tatsuyuki; Igeta, Hirofumi; Iwata, Nakao; Someya, Toshiyuki.
In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 171, No. 6, 01.09.2016, p. 797-805.Research output: Contribution to journal › Article
TY - JOUR
T1 - Rare UNC13B variations and risk of schizophrenia
T2 - Whole-exome sequencing in a multiplex family and follow-up resequencing and a case–control study
AU - Egawa, Jun
AU - Hoya, Satoshi
AU - Watanabe, Yuichiro
AU - Nunokawa, Ayako
AU - Shibuya, Masako
AU - Ikeda, Masashi
AU - Inoue, Emiko
AU - Okuda, Shujiro
AU - Kondo, Kenji
AU - Saito, Takeo
AU - Kaneko, Naoshi
AU - Muratake, Tatsuyuki
AU - Igeta, Hirofumi
AU - Iwata, Nakao
AU - Someya, Toshiyuki
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Rare genomic variations inherited in multiplex schizophrenia families are suggested to play a role in the genetic etiology of the disease. To identify rare variations with large effects on the risk of developing schizophrenia, we performed whole-exome sequencing (WES) in two affected and one unaffected individual of a multiplex family with 10 affected individuals. We also performed follow-up resequencing of the unc-13 homolog B (Caenorhabditis elegans) (UNC13B) gene, a potential risk gene identified by WES, in the multiplex family and undertook a case–control study to investigate association between UNC13B and schizophrenia. UNC13B coding regions (39 exons) from 15 individuals of the multiplex family and 111 affected offspring for whom parental DNA samples were available were resequenced. Rare missense UNC13B variations identified by resequencing were further tested for association with schizophrenia in two independent case–control populations comprising a total of 1,753 patients and 1,602 controls. A rare missense variation (V1525M) in UNC13B was identified by WES in the multiplex family; this variation was present in five of six affected individuals, but not in eight unaffected individuals or one individual of unknown disease status. Resequencing UNC13B coding regions identified five rare missense variations (T103M, M813T, P1349T, I1362T, and V1525M). In the case–control study, there was no significant association between rare missense UNC13B variations and schizophrenia, although single-variant meta-analysis indicated that M813T was nominally associated with schizophrenia. These results do not support a contribution of rare missense UNC13B variations to the genetic etiology of schizophrenia in the Japanese population.
AB - Rare genomic variations inherited in multiplex schizophrenia families are suggested to play a role in the genetic etiology of the disease. To identify rare variations with large effects on the risk of developing schizophrenia, we performed whole-exome sequencing (WES) in two affected and one unaffected individual of a multiplex family with 10 affected individuals. We also performed follow-up resequencing of the unc-13 homolog B (Caenorhabditis elegans) (UNC13B) gene, a potential risk gene identified by WES, in the multiplex family and undertook a case–control study to investigate association between UNC13B and schizophrenia. UNC13B coding regions (39 exons) from 15 individuals of the multiplex family and 111 affected offspring for whom parental DNA samples were available were resequenced. Rare missense UNC13B variations identified by resequencing were further tested for association with schizophrenia in two independent case–control populations comprising a total of 1,753 patients and 1,602 controls. A rare missense variation (V1525M) in UNC13B was identified by WES in the multiplex family; this variation was present in five of six affected individuals, but not in eight unaffected individuals or one individual of unknown disease status. Resequencing UNC13B coding regions identified five rare missense variations (T103M, M813T, P1349T, I1362T, and V1525M). In the case–control study, there was no significant association between rare missense UNC13B variations and schizophrenia, although single-variant meta-analysis indicated that M813T was nominally associated with schizophrenia. These results do not support a contribution of rare missense UNC13B variations to the genetic etiology of schizophrenia in the Japanese population.
UR - http://www.scopus.com/inward/record.url?scp=84961266979&partnerID=8YFLogxK
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U2 - 10.1002/ajmg.b.32444
DO - 10.1002/ajmg.b.32444
M3 - Article
C2 - 26990377
AN - SCOPUS:84961266979
VL - 171
SP - 797
EP - 805
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
SN - 1552-4841
IS - 6
ER -