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    Rights statement: This is the peer reviewed version of the following article:Harold, D, Connolly, S, Riley, BP, et al. Population‐based identity‐by‐descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia. Am J Med Genet Part B. 2019; 180B: 223– 231. https://doi.org/10.1002/ajmg.b.32716 which has been published in final form at https://onlinelibrary.wiley.com/doi/full/10.1002/ajmg.b.32716 This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.

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Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia

Research output: Contribution to journalJournal articlepeer-review

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Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia. / Wellcome Trust Case Control Consortium 2; Schizophrenia Working Group of the Psychiatric Genomics Consortium.

In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics , Vol. 180, No. 3, 01.04.2019, p. 223-231.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Wellcome Trust Case Control Consortium 2 & Schizophrenia Working Group of the Psychiatric Genomics Consortium 2019, 'Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia', American Journal of Medical Genetics Part B: Neuropsychiatric Genetics , vol. 180, no. 3, pp. 223-231. https://doi.org/10.1002/ajmg.b.32716

APA

Wellcome Trust Case Control Consortium 2, & Schizophrenia Working Group of the Psychiatric Genomics Consortium (2019). Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics , 180(3), 223-231. https://doi.org/10.1002/ajmg.b.32716

Vancouver

Wellcome Trust Case Control Consortium 2, Schizophrenia Working Group of the Psychiatric Genomics Consortium. Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics . 2019 Apr 1;180(3):223-231. https://doi.org/10.1002/ajmg.b.32716

Author

Wellcome Trust Case Control Consortium 2 ; Schizophrenia Working Group of the Psychiatric Genomics Consortium. / Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia. In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics . 2019 ; Vol. 180, No. 3. pp. 223-231.

Bibtex

@article{e9054de133a74dda8439bff35c52ca29,
title = "Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia",
abstract = "Genome-wide association studies (GWASs) are highly effective at identifying common risk variants for schizophrenia. Rare risk variants are also important contributors to schizophrenia etiology but, with the exception of large copy number variants, are difficult to detect with GWAS. Exome and genome sequencing, which have accelerated the study of rare variants, are expensive so alternative methods are needed to aid detection of rare variants. Here we re-analyze an Irish schizophrenia GWAS dataset (n = 3,473) by performing identity-by-descent (IBD) mapping followed by exome sequencing of individuals identified as sharing risk haplotypes to search for rare risk variants in coding regions. We identified 45 rare haplotypes (>1 cM) that were significantly more common in cases than controls. By exome sequencing 105 haplotype carriers, we investigated these haplotypes for functional coding variants that could be tested for association in independent GWAS samples. We identified one rare missense variant in PCNT but did not find statistical support for an association with schizophrenia in a replication analysis. However, IBD mapping can prioritize both individual samples and genomic regions for follow-up analysis but genome rather than exome sequencing may be more effective at detecting risk variants on rare haplotypes.",
author = "{Wellcome Trust Case Control Consortium 2} and {Schizophrenia Working Group of the Psychiatric Genomics Consortium} and Denise Harold and Siobhan Connolly and Riley, {Brien P} and Kendler, {Kenneth S} and McCarthy, {Shane E} and McCombie, {William R} and Alex Richards and Owen, {Michael J} and O'Donovan, {Michael C} and James Walters and Gary Donohoe and Michael Gill and Aiden Corvin and Morris, {Derek W} and Jo Knight",
note = "This is the peer reviewed version of the following article:Harold, D, Connolly, S, Riley, BP, et al. Population‐based identity‐by‐descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia. Am J Med Genet Part B. 2019; 180B: 223– 231. https://doi.org/10.1002/ajmg.b.32716 which has been published in final form at https://onlinelibrary.wiley.com/doi/full/10.1002/ajmg.b.32716 This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving. ",
year = "2019",
month = apr,
day = "1",
doi = "10.1002/ajmg.b.32716",
language = "English",
volume = "180",
pages = "223--231",
journal = "American Journal of Medical Genetics Part B: Neuropsychiatric Genetics ",
issn = "1552-4841",
publisher = "Wiley-Liss Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia

AU - Wellcome Trust Case Control Consortium 2

AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium

AU - Harold, Denise

AU - Connolly, Siobhan

AU - Riley, Brien P

AU - Kendler, Kenneth S

AU - McCarthy, Shane E

AU - McCombie, William R

AU - Richards, Alex

AU - Owen, Michael J

AU - O'Donovan, Michael C

AU - Walters, James

AU - Donohoe, Gary

AU - Gill, Michael

AU - Corvin, Aiden

AU - Morris, Derek W

AU - Knight, Jo

N1 - This is the peer reviewed version of the following article:Harold, D, Connolly, S, Riley, BP, et al. Population‐based identity‐by‐descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia. Am J Med Genet Part B. 2019; 180B: 223– 231. https://doi.org/10.1002/ajmg.b.32716 which has been published in final form at https://onlinelibrary.wiley.com/doi/full/10.1002/ajmg.b.32716 This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Genome-wide association studies (GWASs) are highly effective at identifying common risk variants for schizophrenia. Rare risk variants are also important contributors to schizophrenia etiology but, with the exception of large copy number variants, are difficult to detect with GWAS. Exome and genome sequencing, which have accelerated the study of rare variants, are expensive so alternative methods are needed to aid detection of rare variants. Here we re-analyze an Irish schizophrenia GWAS dataset (n = 3,473) by performing identity-by-descent (IBD) mapping followed by exome sequencing of individuals identified as sharing risk haplotypes to search for rare risk variants in coding regions. We identified 45 rare haplotypes (>1 cM) that were significantly more common in cases than controls. By exome sequencing 105 haplotype carriers, we investigated these haplotypes for functional coding variants that could be tested for association in independent GWAS samples. We identified one rare missense variant in PCNT but did not find statistical support for an association with schizophrenia in a replication analysis. However, IBD mapping can prioritize both individual samples and genomic regions for follow-up analysis but genome rather than exome sequencing may be more effective at detecting risk variants on rare haplotypes.

AB - Genome-wide association studies (GWASs) are highly effective at identifying common risk variants for schizophrenia. Rare risk variants are also important contributors to schizophrenia etiology but, with the exception of large copy number variants, are difficult to detect with GWAS. Exome and genome sequencing, which have accelerated the study of rare variants, are expensive so alternative methods are needed to aid detection of rare variants. Here we re-analyze an Irish schizophrenia GWAS dataset (n = 3,473) by performing identity-by-descent (IBD) mapping followed by exome sequencing of individuals identified as sharing risk haplotypes to search for rare risk variants in coding regions. We identified 45 rare haplotypes (>1 cM) that were significantly more common in cases than controls. By exome sequencing 105 haplotype carriers, we investigated these haplotypes for functional coding variants that could be tested for association in independent GWAS samples. We identified one rare missense variant in PCNT but did not find statistical support for an association with schizophrenia in a replication analysis. However, IBD mapping can prioritize both individual samples and genomic regions for follow-up analysis but genome rather than exome sequencing may be more effective at detecting risk variants on rare haplotypes.

U2 - 10.1002/ajmg.b.32716

DO - 10.1002/ajmg.b.32716

M3 - Journal article

C2 - 30801977

VL - 180

SP - 223

EP - 231

JO - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

SN - 1552-4841

IS - 3

ER -