دورية أكاديمية
Mutation intolerant genes and targets of FMRP are enriched for nonsynonymous alleles in schizophrenia.
| العنوان: | Mutation intolerant genes and targets of FMRP are enriched for nonsynonymous alleles in schizophrenia. |
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| المؤلفون: | Leonenko, G, Richards, AL, Walters, JT, Pocklington, A, Chambert, K, Al Eissa, MM, Sharp, SI, O'Brien, NL, Curtis, D, Bass, NJ, McQuillin, A, Hultman, C, Moran, JL, McCarroll, SA, Sklar, P, Neale, BM, Holmans, PA, Owen, MJ, Sullivan, PF, O'Donovan, MC |
| سنة النشر: | 2017 |
| المجموعة: | Queen Mary University of London: Queen Mary Research Online (QMRO) |
| مصطلحات موضوعية: | FMRP, association, exome chip, rare variation, schizophrenia, Case-Control Studies, Cohort Studies, Exome, Follow-Up Studies, Fragile X Mental Retardation Protein, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Mutation, Polymorphism, Single Nucleotide, Prognosis |
| الوصف: | Risk of schizophrenia is conferred by alleles occurring across the full spectrum of frequencies from common SNPs of weak effect through to ultra rare alleles, some of which may be moderately to highly penetrant. Previous studies have suggested that some of the risk of schizophrenia is attributable to uncommon alleles represented on Illumina exome arrays. Here, we present the largest study of exomic variation in schizophrenia to date, using samples from the United Kingdom and Sweden (10,011 schizophrenia cases and 13,791 controls). Single variants, genes, and gene sets were analyzed for association with schizophrenia. No single variant or gene reached genome-wide significance. Among candidate gene sets, we found significant enrichment for rare alleles (minor allele frequency [MAF] < 0.001) in genes intolerant of loss-of-function (LoF) variation and in genes whose messenger RNAs bind to fragile X mental retardation protein (FMRP). We further delineate the genetic architecture of schizophrenia by excluding a role for uncommon exomic variants (0.01 ≤ MAF ≥ 0.001) that confer a relatively large effect (odds ratio [OR] > 4). We also show risk alleles within this frequency range exist, but confer smaller effects and should be identified by larger studies. ; Swedish Research Council. Grant Number: D0886501 Seventh Framework Programme. Grant Number: HEALTH-F2-2010-241909 Medical Research Council. Grant Numbers: G0800509, G0801418 National Institute of Mental Health. Grant Number: R01 MH077139 |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 724 - 731 |
| اللغة: | English |
| العلاقة: | Am J Med Genet B Neuropsychiatr Genet; http://qmro.qmul.ac.uk/xmlui/handle/123456789/25203Test |
| DOI: | 10.1002/ajmg.b.32560 |
| الإتاحة: | https://doi.org/10.1002/ajmg.b.32560Test http://qmro.qmul.ac.uk/xmlui/handle/123456789/25203Test |
| رقم الانضمام: | edsbas.6248AF29 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/ajmg.b.32560 |
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