Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease
Data(s) |
01/10/2009
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Resumo |
We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 x 10(-157)) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 x 10(-9)) and 5. to the PICALM gene (rs3851179, P = 1.9 x 10(-8)). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 x 10(-10), odds ratio = 0.86; rs3851179, P = 1.3 x 10(-9), odds ratio = 0.86). |
Formato |
application/pdf |
Identificador |
http://dx.doi.org/10.1038/ng.440 http://www.scopus.com/inward/record.url?scp=70349558522&partnerID=8YFLogxK |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/openAccess |
Fonte |
Harold , D , Abraham , R , Hollingworth , P , Sims , R , Gerrish , A , Hamshere , M L , Pahwa , J S , Moskvina , V , Dowzell , K , Williams , A , Jones , N , Thomas , C , Stretton , A , Morgan , A R , Lovestone , S , Powell , J , Proitsi , P , Lupton , M K , Brayne , C , Rubinsztein , D C , Gill , M , Lawlor , B , Lynch , A , Morgan , K , Brown , K S , Passmore , P , Craig , D , McGuinness , J , Todd , S , Holmes , C , Mann , D , Smith , A D , Love , S , Kehoe , P G , Hardy , J , Mead , S , Fox , N , Rossor , M , Collinge , J , Maier , W , Jessen , F , Schurmann , B , Van Den Bussche , H , Heuser , I , Kornhuber , J , Wiltfang , J , Dichgans , M , Frolich , L , Hampel , H , Hull , M , Rujescu , D , Goate , A M , Kauwe , J S K , Cruchaga , C , Nowotny , P , Morris , J C , Mayo , K , Sleegers , K , Bettens , K , Engelborghs , S , De Deyn , P P , Van Broeckhoven , C , Livingston , G , Bass , N J , Gurling , H , McQuillin , A , Gwilliam , R , Deloukas , P , Al-Chalabi , A , Shaw , C E , Tsolaki , M , Singleton , A B , Guerreiro , R , Muhleisen , T W , Nothen , M M , Moebus , S , Jockel , K H , Klopp , N , Wichmann , H E , Carrasquillo , M M , Pankratz , V S , Younkin , S G , Holmans , P A , O'Donovan , M , Owen , M J & Williams , J 2009 , ' Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease ' Nature Genetics , vol 41 , no. 10 , pp. 1088-1093 . DOI: 10.1038/ng.440 |
Palavras-Chave | #/dk/atira/pure/subjectarea/asjc/1300/1311 #Genetics |
Tipo |
article |