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Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia
- Source :
- American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 180(3), 223. Wiley-Liss Inc., Harold, D, Connolly, S, Riley, B P, Kendler, K S, McCarthy, S E, McCombie, W R, Richards, A, Owen, M J, O'Donovan, M C, Walters, J, Wellcome Trust Case Control Consortium 2, The Schizophrenia Working Group of the Psychiatric Genomics Consortium, Donohoe, G, Gill, M, Corvin, A & Morris, D W 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, American journal of medical genetics. Part B, Neuropsychiatric genetics, 180(3), 223-231. Wiley-Liss Inc., Am J Med Genet B Neuropsychiatr Genet, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, vol 180, iss 3
- Publication Year :
- 2019
- Publisher :
- WILEY, 2019.
-
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. National Institutes of Health, Grant/Award Numbers: R01‐MH041953, R01‐MH083094; Science Foundation Ireland, Grant/Award Numbers: 08/IN.1/B1916, 12/IP/1359, 12/IP/1670; Wellcome Trust, Grant/Award Number: 085475/B/08/Z peer-reviewed
- Subjects :
- Male
Genome-wide association study
WHOLE-GENOME ASSOCIATION
Identity by descent
0302 clinical medicine
Risk Factors
Databases, Genetic
2.1 Biological and endogenous factors
GWAS
Exome
Copy-number variation
Aetiology
Genetics (clinical)
Exome sequencing
Genetics & Heredity
Psychiatry
Schizophrenia Working Group of the Psychiatric Genomics Consortium
0303 health sciences
Chromosome Mapping
Middle Aged
Serious Mental Illness
3. Good health
Psychiatry and Mental health
Mental Health
DISEASES
Female
BURDEN
Sequence Analysis
Life Sciences & Biomedicine
Adult
GENES
DNA Copy Number Variations
Genotype
DISORDERS
Clinical Sciences
Single-nucleotide polymorphism
Computational biology
Biology
IBD mapping
Article
Databases
03 medical and health sciences
Cellular and Molecular Neuroscience
Genetic
Clinical Research
Exome Sequencing
rare variants
Genetics
Humans
Genetic Predisposition to Disease
AUTISM
Genome‐wide association studies (GWASs)
030304 developmental biology
Genetic association
Science & Technology
risk variants
Prevention
Wellcome Trust Case Control Consortium 2
Human Genome
Haplotype
Neurosciences
DNA
Sequence Analysis, DNA
Brain Disorders
Haplotypes
DE-NOVO MUTATIONS
Case-Control Studies
API
Schizophrenia
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 15524841
- Database :
- OpenAIRE
- Journal :
- American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 180(3), 223. Wiley-Liss Inc., Harold, D, Connolly, S, Riley, B P, Kendler, K S, McCarthy, S E, McCombie, W R, Richards, A, Owen, M J, O'Donovan, M C, Walters, J, Wellcome Trust Case Control Consortium 2, The Schizophrenia Working Group of the Psychiatric Genomics Consortium, Donohoe, G, Gill, M, Corvin, A & Morris, D W 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, American journal of medical genetics. Part B, Neuropsychiatric genetics, 180(3), 223-231. Wiley-Liss Inc., Am J Med Genet B Neuropsychiatr Genet, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, vol 180, iss 3
- Accession number :
- edsair.doi.dedup.....e6b27234803db5d60315706f8029d6c6