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

Hirofumi Igeta, Yuichiro Watanabe, Ryo Morikawa, Masashi Ikeda, Ikuo Otsuka, Satoshi Hoya, Masataka Koizumi, Jun Egawa, Akitoyo Hishimoto, Nakao Iwata, Toshiyuki Someya

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)2353-2363
Number of pages11
JournalNeuropsychiatric Disease and Treatment
Volume15
DOIs
Publication statusPublished - 01-01-2019

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All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Igeta, Hirofumi ; Watanabe, Yuichiro ; Morikawa, Ryo ; Ikeda, Masashi ; Otsuka, Ikuo ; Hoya, Satoshi ; Koizumi, Masataka ; Egawa, Jun ; Hishimoto, Akitoyo ; Iwata, Nakao ; Someya, Toshiyuki. / 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. In: Neuropsychiatric Disease and Treatment. 2019 ; Vol. 15. pp. 2353-2363.
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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.",
author = "Hirofumi Igeta and Yuichiro Watanabe and Ryo Morikawa and Masashi Ikeda and Ikuo Otsuka and Satoshi Hoya and Masataka Koizumi and Jun Egawa and Akitoyo Hishimoto and Nakao Iwata and Toshiyuki Someya",
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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 journalArticle

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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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