Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer’s disease
| العنوان: | Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer’s disease |
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| المؤلفون: | Sudha Seshadri, John Hardy, Wolfgang Maier, Janet C Harwood, Emily Baker, Carol Brayne, Julie Williams, Lesley Jones, Gerard D. Schellenberg, Reinhard Heun, Frank Jessen, Valentina Escott-Price, Matthew Hill, Oliver Peters, John Powell, Dobril Ivanov, Peter Passmore, Martin Dichgans, Lutz Frölich, Alfredo Ramirez, Aura Frizzati, Alison Goate, Kevin Morgan, Paul Morgan, Carlos Cruchaga, Ganna Leonenko, Gianfranco Spalletta, Paola Bossù, Michael Gill, Clive Holmes, Simon Mead, Detelina Grozeva, Peter Holmans, Philippe Amouyel, Rebecca Sims, Nicholas D. Allen |
| المساهمون: | Baker, Emily [0000-0001-5691-597X], Grozeva, Detelina [0000-0003-3239-8415], Brayne, Carol [0000-0001-5307-663X], Mead, Simon [0000-0002-4326-1468], Ramirez, Alfredo [0000-0003-4991-763X], Ivanov, Dobril [0000-0001-6271-6301], Hill, Matthew [0000-0001-6776-8709], Holmans, Peter [0000-0003-0870-9412], Schellenberg, Gerard D [0000-0003-1115-2475], Apollo - University of Cambridge Repository, van Duijn, Cornelia [0000-0002-2374-9204], Williams, Julie [0000-0002-4069-0259] |
| المصدر: | PLoS ONE PLoS ONE, Vol 14, Iss 7, p e0218111 (2019) PLOS ONE 14(7), e0218111 (2019). doi:10.1371/journal.pone.0218111 |
| بيانات النشر: | Public Library of Science, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, DNA Repair, Gene Expression, Social Sciences, genetics [Alzheimer Disease], genetics [Cholesterol], Genome-wide association study, Alzheimer's Disease, Biochemistry, IGAP consortia, pathology [Centrosome], pathology [Alzheimer Disease], 0302 clinical medicine, Sociology, metabolism [Centrosome], Consortia, Medicine and Health Sciences, genetics [Amyloid beta-Peptides], Genetics, Regulation of gene expression, metabolism [Inflammation], Multidisciplinary, biology, metabolism [Proteins], Neurodegenerative Diseases, Nuclear Receptor Subfamily 1, Group F, Member 1, Genomics, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Circadian Rhythm, Circadian Rhythms, Cholesterol, Neurology, Medicine, Female, metabolism [Alzheimer Disease], Research Article, medicine.medical_specialty, genetics [Circadian Rhythm], Amyloid beta, Science, Lipoproteins, metabolism [Amyloid beta-Peptides], Single-nucleotide polymorphism, genetics [Energy Metabolism], Polymorphism, Single Nucleotide, GERAD Consortium, Apolipoprotein Genes, Molecular Genetics, genetics [Inflammation], 03 medical and health sciences, Alzheimer Disease, genetics [Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha], Molecular genetics, Mental Health and Psychiatry, medicine, Genome-Wide Association Studies, GERAD/PERADES, Dementia, Humans, genetics [DNA Damage], Gene Regulation, ddc:610, genetics [DNA Repair], Gene, Molecular Biology, EADI Consortium, pathology [Inflammation], Centrosome, Inflammation, Amyloid beta-Peptides, Genome, Human, Biology and Life Sciences, Proteins, Computational Biology, Human Genetics, metabolism [Cholesterol], medicine.disease, Genome Analysis, ADGC Consortium, genetics [Proteins], 030104 developmental biology, metabolism [Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha], CHARGE Consortium, biology.protein, Energy Metabolism, Chronobiology, 030217 neurology & neurosurgery, genetics [Nuclear Receptor Subfamily 1, Group F, Member 1], metabolism [Nuclear Receptor Subfamily 1, Group F, Member 1], DNA Damage, Genome-Wide Association Study |
| الوصف: | A novel POLARIS gene-based analysis approach was employed to compute gene-based polygenic risk score (PRS) for all individuals in the latest HRC imputed GERAD (N cases=3,332 and N controls=9,832) data using the International Genomics of Alzheimer’s Project summary statistics (N cases=13,676 and N controls=27,322, excluding GERAD subjects) to identify the SNPs and weight their risk alleles for the PRS score. SNPs were assigned to known, protein coding genes using GENCODE (v19). SNPs are assigned using both 1) no window around the gene and 2) a window of 35kb upstream and 10kb downstream to include transcriptional regulatory elements. The overall association of a gene is determined using a logistic regression model, adjusting for population covariates. Three novel gene-wide significant genes were determined from the POLARIS gene-based analysis using a gene window; PPARGC1A, RORA and ZNF423 . The ZNF423 gene resides in an Alzheimer’s disease (AD)-specific protein network which also includes other AD-related genes. The PPARGC1A gene has been linked to energy metabolism and the generation of amyloid beta plaques and the RORA has strong links with genes which are differentially expressed in the hippocampus. We also demonstrate no enrichment for genes in either loss of function intolerant or conserved noncoding sequence regions. |
| وصف الملف: | application/pdf; application/vnd.openxmlformats-officedocument.wordprocessingml.document |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::caad960b1629d3f30b5bbfa303783204Test http://europepmc.org/articles/PMC6613773Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....caad960b1629d3f30b5bbfa303783204 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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