Whole genome sequencing of 91 multiplex schizophrenia families reveals increased burden of rare, exonic copy number variation in schizophrenia probands and genetic heterogeneity

Research output: Contribution to journalArticle

1 Citation (Scopus)
127 Downloads (Pure)

Abstract

The importance of genomic copy number variants (CNVs) has long been recognized in the etiology of neurodevelopmental diseases. We report here the results from the CNV analysis of whole-genome sequences from 91 multiplex schizophrenia families. Employing four algorithms (CNVnator, Cn.mops, DELLY and LUMPY) to identify CNVs, we find 1231 rare deletions and 287 rare duplications in 300 individuals (77 with schizophrenia (SZ), 32 with schizoaffective disorder (SAD), 82 with another neuropsychiatric diagnosis and 109 unaffected). The size of the CNVs ranges from a few hundred base-pairs to about 1.3 Mb. The total burden of CNVs does not differ significantly between affected (SZ and SAD) and unaffected individuals. Parent-to-child transmission rate for rare CNVs affecting exonic regions is significantly higher for affected (SZ and SAD) probands as compared to their siblings, but rates for all CNVs is not. We observe heterogeneity between families in terms of genes involved in CNVs, and find several CNVs involving genes previously implicated in either schizophrenia or other neuropsychiatric disorders.

Original languageEnglish
Pages (from-to)337-345
JournalSchizophrenia Research
Volume197
DOIs
Publication statusPublished - Jul 2018

Fingerprint

Genetic Heterogeneity
Schizophrenia
Genome
Psychotic Disorders
Base Pairing
Genes
Siblings

Cite this

@article{b2bc0fd676cf4c9aa49af973550e2deb,
title = "Whole genome sequencing of 91 multiplex schizophrenia families reveals increased burden of rare, exonic copy number variation in schizophrenia probands and genetic heterogeneity",
abstract = "The importance of genomic copy number variants (CNVs) has long been recognized in the etiology of neurodevelopmental diseases. We report here the results from the CNV analysis of whole-genome sequences from 91 multiplex schizophrenia families. Employing four algorithms (CNVnator, Cn.mops, DELLY and LUMPY) to identify CNVs, we find 1231 rare deletions and 287 rare duplications in 300 individuals (77 with schizophrenia (SZ), 32 with schizoaffective disorder (SAD), 82 with another neuropsychiatric diagnosis and 109 unaffected). The size of the CNVs ranges from a few hundred base-pairs to about 1.3 Mb. The total burden of CNVs does not differ significantly between affected (SZ and SAD) and unaffected individuals. Parent-to-child transmission rate for rare CNVs affecting exonic regions is significantly higher for affected (SZ and SAD) probands as compared to their siblings, but rates for all CNVs is not. We observe heterogeneity between families in terms of genes involved in CNVs, and find several CNVs involving genes previously implicated in either schizophrenia or other neuropsychiatric disorders.",
keywords = "Copy number variation, Family study, Schizophrenia, Whole-genome sequence",
author = "Khan, {Fayeza F.} and Melton, {Phillip E.} and McCarthy, {Nina S.} and Bharti Morar and John Blangero and Moses, {Eric K.} and Assen Jablensky",
year = "2018",
month = "7",
doi = "10.1016/j.schres.2018.02.034",
language = "English",
volume = "197",
pages = "337--345",
journal = "Schizophrenia Research",
issn = "0920-9964",
publisher = "Pergamon",

}

TY - JOUR

T1 - Whole genome sequencing of 91 multiplex schizophrenia families reveals increased burden of rare, exonic copy number variation in schizophrenia probands and genetic heterogeneity

AU - Khan, Fayeza F.

AU - Melton, Phillip E.

AU - McCarthy, Nina S.

AU - Morar, Bharti

AU - Blangero, John

AU - Moses, Eric K.

AU - Jablensky, Assen

PY - 2018/7

Y1 - 2018/7

N2 - The importance of genomic copy number variants (CNVs) has long been recognized in the etiology of neurodevelopmental diseases. We report here the results from the CNV analysis of whole-genome sequences from 91 multiplex schizophrenia families. Employing four algorithms (CNVnator, Cn.mops, DELLY and LUMPY) to identify CNVs, we find 1231 rare deletions and 287 rare duplications in 300 individuals (77 with schizophrenia (SZ), 32 with schizoaffective disorder (SAD), 82 with another neuropsychiatric diagnosis and 109 unaffected). The size of the CNVs ranges from a few hundred base-pairs to about 1.3 Mb. The total burden of CNVs does not differ significantly between affected (SZ and SAD) and unaffected individuals. Parent-to-child transmission rate for rare CNVs affecting exonic regions is significantly higher for affected (SZ and SAD) probands as compared to their siblings, but rates for all CNVs is not. We observe heterogeneity between families in terms of genes involved in CNVs, and find several CNVs involving genes previously implicated in either schizophrenia or other neuropsychiatric disorders.

AB - The importance of genomic copy number variants (CNVs) has long been recognized in the etiology of neurodevelopmental diseases. We report here the results from the CNV analysis of whole-genome sequences from 91 multiplex schizophrenia families. Employing four algorithms (CNVnator, Cn.mops, DELLY and LUMPY) to identify CNVs, we find 1231 rare deletions and 287 rare duplications in 300 individuals (77 with schizophrenia (SZ), 32 with schizoaffective disorder (SAD), 82 with another neuropsychiatric diagnosis and 109 unaffected). The size of the CNVs ranges from a few hundred base-pairs to about 1.3 Mb. The total burden of CNVs does not differ significantly between affected (SZ and SAD) and unaffected individuals. Parent-to-child transmission rate for rare CNVs affecting exonic regions is significantly higher for affected (SZ and SAD) probands as compared to their siblings, but rates for all CNVs is not. We observe heterogeneity between families in terms of genes involved in CNVs, and find several CNVs involving genes previously implicated in either schizophrenia or other neuropsychiatric disorders.

KW - Copy number variation

KW - Family study

KW - Schizophrenia

KW - Whole-genome sequence

UR - http://www.scopus.com/inward/record.url?scp=85042452321&partnerID=8YFLogxK

U2 - 10.1016/j.schres.2018.02.034

DO - 10.1016/j.schres.2018.02.034

M3 - Article

VL - 197

SP - 337

EP - 345

JO - Schizophrenia Research

JF - Schizophrenia Research

SN - 0920-9964

ER -