Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia
Harold, D (Harold, Denise)5,6; Harold, D (Harold, Denise)6; Riley, BP (Riley, Brien P.)3; Kendler, KS (Kendler, Kenneth S.)3; McCarthy, SE (McCarthy, Shane E.)2; McCombie, WR (McCombie, William R.)2; Richards, A (Richards, Alex)1; Owen, MJ (Owen, Michael J.)1; Walters, J (Walters, James)1
刊名AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
2019
卷号180期号:3页码:223-231
关键词GWAS IBD mapping rare variants
ISSN号1552-4841
DOI10.1002/ajmg.b.32716
文献子类实证研究
英文摘要

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.

内容类型期刊论文
源URL[http://ir.psych.ac.cn/handle/311026/34151]  
专题心理研究所_健康与遗传心理学研究室
作者单位1.Cognitive Genetics and Cognitive Therapy Group, Neuroimaging, Cognition & Genomics (NICOG) Centre & NCBES Galway Neuroscience Centre, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland
2.MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, United Kingdom
3.Departments of Psychiatry and Human Genetics, Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia
4.The Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York
5.School of Biotechnology, Dublin City University, Dublin, Ireland
6.Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine and Discipline of Psychiatry, Trinity College Dublin, Dublin, Ireland
推荐引用方式
GB/T 7714
Harold, D ,Harold, D ,Riley, BP ,et al. Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia[J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS,2019,180(3):223-231.
APA Harold, D .,Harold, D .,Riley, BP .,Kendler, KS .,McCarthy, SE .,...&Walters, J .(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.
MLA Harold, D ,et al."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(2019):223-231.
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