Abstract
Purpose: Whole-exome sequencing (WES) of multiplex families is a promising strategy for identifying causative variations for common diseases. To identify rare recessive risk variations for schizophrenia, we performed a WES study in a consanguineous family with affected siblings. We then performed follow-up sequencing of SPATA7 in schizophrenia-affected families. In addition, we performed a case-control study to investigate association between SPATA7 variations and schizophrenia. Patients and methods: WES was performed on two affected siblings and their unaffected parents, who were second cousins, of a multiplex schizophrenia family. Subsequently, we sequenced the coding region of SPATA7, a potential risk gene identified by the WES analysis, in 142 affected offspring from 137 families for whom parental DNA samples were available. We further tested rare recessive SPATA7 variations, identified by WES and sequencing, for associations with schizophrenia in 2,756 patients and 2,646 controls. Results: Our WES analysis identified rare compound heterozygous missense SPATA7 variations, p.Asp134Gly and p.Ile332Thr, in both affected siblings. Sequencing SPATA7 coding regions from 137 families identified no rare recessive variations in affected offspring. In the case-control study, we did not detect the rare compound heterozygous SPATA7 missense variations in patients or controls. Conclusion: Our data does not support the role of the rare compound heterozygous SPATA7 missense variations p.Asp134Gly and p.Ile332Thr in conferring a substantial risk of schizophrenia.
| Original language | English |
|---|---|
| Pages (from-to) | 2353-2363 |
| Number of pages | 11 |
| Journal | Neuropsychiatric Disease and Treatment |
| Volume | 15 |
| DOIs | |
| Publication status | Published - 01-01-2019 |
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All Science Journal Classification (ASJC) codes
- Psychiatry and Mental health
- Biological Psychiatry
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Rare compound heterozygous missense SPATA7 variations and risk of schizophrenia; whole-exome sequencing in a consanguineous family with affected siblings, follow-up sequencing and a casecontrol study. / Igeta, Hirofumi; Watanabe, Yuichiro; Morikawa, Ryo; Ikeda, Masashi; Otsuka, Ikuo; Hoya, Satoshi; Koizumi, Masataka; Egawa, Jun; Hishimoto, Akitoyo; Iwata, Nakao; Someya, Toshiyuki.
In: Neuropsychiatric Disease and Treatment, Vol. 15, 01.01.2019, p. 2353-2363.Research output: Contribution to journal › Article
TY - JOUR
T1 - Rare compound heterozygous missense SPATA7 variations and risk of schizophrenia; whole-exome sequencing in a consanguineous family with affected siblings, follow-up sequencing and a casecontrol study
AU - Igeta, Hirofumi
AU - Watanabe, Yuichiro
AU - Morikawa, Ryo
AU - Ikeda, Masashi
AU - Otsuka, Ikuo
AU - Hoya, Satoshi
AU - Koizumi, Masataka
AU - Egawa, Jun
AU - Hishimoto, Akitoyo
AU - Iwata, Nakao
AU - Someya, Toshiyuki
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Purpose: Whole-exome sequencing (WES) of multiplex families is a promising strategy for identifying causative variations for common diseases. To identify rare recessive risk variations for schizophrenia, we performed a WES study in a consanguineous family with affected siblings. We then performed follow-up sequencing of SPATA7 in schizophrenia-affected families. In addition, we performed a case-control study to investigate association between SPATA7 variations and schizophrenia. Patients and methods: WES was performed on two affected siblings and their unaffected parents, who were second cousins, of a multiplex schizophrenia family. Subsequently, we sequenced the coding region of SPATA7, a potential risk gene identified by the WES analysis, in 142 affected offspring from 137 families for whom parental DNA samples were available. We further tested rare recessive SPATA7 variations, identified by WES and sequencing, for associations with schizophrenia in 2,756 patients and 2,646 controls. Results: Our WES analysis identified rare compound heterozygous missense SPATA7 variations, p.Asp134Gly and p.Ile332Thr, in both affected siblings. Sequencing SPATA7 coding regions from 137 families identified no rare recessive variations in affected offspring. In the case-control study, we did not detect the rare compound heterozygous SPATA7 missense variations in patients or controls. Conclusion: Our data does not support the role of the rare compound heterozygous SPATA7 missense variations p.Asp134Gly and p.Ile332Thr in conferring a substantial risk of schizophrenia.
AB - Purpose: Whole-exome sequencing (WES) of multiplex families is a promising strategy for identifying causative variations for common diseases. To identify rare recessive risk variations for schizophrenia, we performed a WES study in a consanguineous family with affected siblings. We then performed follow-up sequencing of SPATA7 in schizophrenia-affected families. In addition, we performed a case-control study to investigate association between SPATA7 variations and schizophrenia. Patients and methods: WES was performed on two affected siblings and their unaffected parents, who were second cousins, of a multiplex schizophrenia family. Subsequently, we sequenced the coding region of SPATA7, a potential risk gene identified by the WES analysis, in 142 affected offspring from 137 families for whom parental DNA samples were available. We further tested rare recessive SPATA7 variations, identified by WES and sequencing, for associations with schizophrenia in 2,756 patients and 2,646 controls. Results: Our WES analysis identified rare compound heterozygous missense SPATA7 variations, p.Asp134Gly and p.Ile332Thr, in both affected siblings. Sequencing SPATA7 coding regions from 137 families identified no rare recessive variations in affected offspring. In the case-control study, we did not detect the rare compound heterozygous SPATA7 missense variations in patients or controls. Conclusion: Our data does not support the role of the rare compound heterozygous SPATA7 missense variations p.Asp134Gly and p.Ile332Thr in conferring a substantial risk of schizophrenia.
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U2 - 10.2147/NDT.S218773
DO - 10.2147/NDT.S218773
M3 - Article
AN - SCOPUS:85073354636
VL - 15
SP - 2353
EP - 2363
JO - Neuropsychiatric Disease and Treatment
JF - Neuropsychiatric Disease and Treatment
SN - 1176-6328
ER -