Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease.

Nat Genet 2009 Oct 6;41(10):1088-93. Epub 2009 Sep 6.

Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK.

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).

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http://dx.doi.org/10.1038/ng.440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845877PMC
October 2009
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References

(Supplied by CrossRef)
Article in Genome Med.
D Avramopoulos et al.
Genome Med. 2009
Article in BMC Med. Genomics
R Abraham et al.
BMC Med. Genomics 2008
Article in Am. J. Hum. Genet.
GW Beecham et al.
Am. J. Hum. Genet. 2009
Article in Am. J. Hum. Genet.
L Bertram et al.
Am. J. Hum. Genet. 2008
Article in Nat. Genet.
MM Carrasquillo et al.
Nat. Genet. 2009
Article in J. Clin. Psychiatry
KD Coon et al.
J. Clin. Psychiatry 2007
Article in Hum. Mol. Genet.
A Grupe et al.
Hum. Mol. Genet. 2007
Article in Arch. Neurol.
H Li et al.
Arch. Neurol. 2008
Article in Neuron
EM Reiman et al.
Neuron 2007
Article in Biometrics
B Devlin et al.
Biometrics 1999

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