Baker, Emily, Sims, Rebecca, Leonenko, Ganna, Frizzati, Aura, Harwood, Janet C., Grozeva, Detelina ORCID: 0000-0003-3239-8415, Morgan, Kevin, Passmore, Peter, Holmes, Clive, Powell, John, Brayne, Carol ORCID: 0000-0001-5307-663X, Gill, Michael, Mead, Simon, Bossu, Paola, Spalletta, Gianfranco, Cruchaga, Carlos, Maier, Wolfgang, Heun, Reinhard, Jessen, Frank, Peters, Oliver, Dichgans, Martin, FroeLich, Lutz, Ramirez, Alfredo ORCID: 0000-0003-4991-763X, Jones, Lesley, Hardy, John ORCID: 0000-0002-3122-0423, Ivanov, Dobril, Hill, Matthew ORCID: 0000-0001-6776-8709, Holmans, Peter, Allen, Nicholas D., Morgan, B. Paul, Seshadri, Sudha ORCID: 0000-0001-6135-2622, Schellenberg, Gerard D., Amouyel, Philippe, Williams, Julie ORCID: 0000-0002-4069-0259 and Escott-Price, Valentina (2019). Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer's disease. PLoS One, 14 (7). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Late onset Alzheimer's disease is the most common form of dementia for which about 30 susceptibility loci have been reported. The aim of the current study is to identify novel genes associated with Alzheimer's disease using the largest up-to-date reference single nucleotide polymorphism (SNP) panel, the most accurate imputation software and a novel gene-based analysis approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 million genotypes from 17,008 Alzheimer's cases and 37,154 controls. In addition to earlier reported genes, we detected three novel gene-wide significant loci PPARGC1A (p = 2.2 x 10(-6)), RORA (p = 7.4 x 10(-7)) and ZNF423 (p = 2.1 x 10(-6)). PPARGC1A and RORA are involved in circadian rhythm; circadian disturbances are one of the earliest symptoms of Alzheimer's disease. PPARGC1A is additionally linked to energy metabolism and the generation of amyloid beta plaques. RORA is involved in a variety of functions apart from circadian rhythm, such as cholesterol metabolism and inflammation. The ZNF423 gene resides in an Alzheimer's disease-specific protein network and is likely involved with centrosomes and DNA damage repair.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Baker, EmilyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sims, RebeccaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leonenko, GannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frizzati, AuraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Harwood, Janet C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grozeva, DetelinaUNSPECIFIEDorcid.org/0000-0003-3239-8415UNSPECIFIED
Morgan, KevinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Passmore, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holmes, CliveUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Powell, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brayne, CarolUNSPECIFIEDorcid.org/0000-0001-5307-663XUNSPECIFIED
Gill, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mead, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bossu, PaolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spalletta, GianfrancoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cruchaga, CarlosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maier, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heun, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jessen, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peters, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dichgans, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
FroeLich, LutzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramirez, AlfredoUNSPECIFIEDorcid.org/0000-0003-4991-763XUNSPECIFIED
Jones, LesleyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hardy, JohnUNSPECIFIEDorcid.org/0000-0002-3122-0423UNSPECIFIED
Ivanov, DobrilUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hill, MatthewUNSPECIFIEDorcid.org/0000-0001-6776-8709UNSPECIFIED
Holmans, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Allen, Nicholas D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morgan, B. PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seshadri, SudhaUNSPECIFIEDorcid.org/0000-0001-6135-2622UNSPECIFIED
Schellenberg, Gerard D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Amouyel, PhilippeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Williams, JulieUNSPECIFIEDorcid.org/0000-0002-4069-0259UNSPECIFIED
Escott-Price, ValentinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-135338
DOI: 10.1371/journal.pone.0218111
Journal or Publication Title: PLoS One
Volume: 14
Number: 7
Date: 2019
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
COMMON VARIANTS; PGC-1-ALPHA; DIFFERENTIATION; ZNF423; ALPHA; ANNOTATION; GENERATION; IMMUNITY; BRAIN; CD2APMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13533

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