TY - JOUR
T1 - Meta-analysis of the association between variants in SORL1 and Alzheimer disease
AU - Reitz, Christiane
AU - Cheng, Rong
AU - Rogaeva, Ekaterina
AU - Lee, Joseph H.
AU - Tokuhiro, Shinya
AU - Zou, Fanggeng
AU - Bettens, Karolien
AU - Sleegers, Kristel
AU - Tan, Eng King
AU - Kimura, Ryo
AU - Shibata, Nobuto
AU - Arai, Heii
AU - Kamboh, M. Ilyas
AU - Prince, Jonathan A.
AU - Maier, Wolfgang
AU - Riemenschneider, Matthias
AU - Owen, Michael
AU - Harold, Denise
AU - Hollingworth, Paul
AU - Cellini, Elena
AU - Sorbi, Sandro
AU - Nacmias, Benedetta
AU - Takeda, Masatoshi
AU - Pericak-Vance, Margaret A.
AU - Haines, Jonathan L.
AU - Younkin, Steven
AU - Williams, Julie
AU - Van Broeckhoven, Christine
AU - Farrer, Lindsay A.
AU - St George-Hyslop, Peter H.
AU - Mayeux, Richard
PY - 2011/1
Y1 - 2011/1
N2 - Objective: To reexamine the association between the neuronal sortilin-related receptor gene (SORL1) and Alzheimer disease (AD). Design: Comprehensive and unbiased meta-analysis of all published and unpublished data from case-control studies for the SORL1 single-nucleotide polymorphisms (SNPs) that had been repeatedly assessed across studies. Setting: Academic research institutions in the United States, the Netherlands, Canada, Belgium, the United Kingdom, Singapore, Japan, Sweden, Germany, France, and Italy. Participants: All published white and Asian case-control data sets, which included a total of 12 464 cases and 17 929 controls. Main Outcome Measures: Alzheimer disease according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) and theNational Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (now known as the Alzheimer's Association). Results: In the white data sets, several markers were associated with AD after correction for multiple testing, including previously reported SNPs 8, 9, and 10 (P < .001). In addition, the C-G-C haplotype at SNPs 8 through 10 was associated with AD risk (P < .001). In the combined Asian data sets, SNPs 19 and 23 through 25 were associated withADrisk (P < .001). The disease-associated alleles at SNPs 8, 9, and 10 (120 873 131-120 886 175 base pairs [bp]; C-G-C alleles), at SNP 19 (120 953 300 bp; G allele), and at SNPs 24 through 25 (120 988 611 bp; T and C alleles) were the same previously reported alleles. The SNPs 4 through 5, 8 through 10, 12, and 19 through 25 belong to distinct linkage disequilibrium blocks. The same alleles at SNPs 8 through 10 (C-G-C), 19 (G), and 24 and 25 (T and C) have also been associated with AD endophenotypes, including white matter hyperintensities and hippocampal atrophy on magnetic resonance imaging, cerebrospinal fluid measures of amyloid β-peptide 42, and full-length SORL1 expression in the human brain. Conclusion: This comprehensive meta-analysis provides confirmatory evidence that multiple SORL1 variants in distinct linkage disequilibrium blocks are associated with AD.
AB - Objective: To reexamine the association between the neuronal sortilin-related receptor gene (SORL1) and Alzheimer disease (AD). Design: Comprehensive and unbiased meta-analysis of all published and unpublished data from case-control studies for the SORL1 single-nucleotide polymorphisms (SNPs) that had been repeatedly assessed across studies. Setting: Academic research institutions in the United States, the Netherlands, Canada, Belgium, the United Kingdom, Singapore, Japan, Sweden, Germany, France, and Italy. Participants: All published white and Asian case-control data sets, which included a total of 12 464 cases and 17 929 controls. Main Outcome Measures: Alzheimer disease according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) and theNational Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (now known as the Alzheimer's Association). Results: In the white data sets, several markers were associated with AD after correction for multiple testing, including previously reported SNPs 8, 9, and 10 (P < .001). In addition, the C-G-C haplotype at SNPs 8 through 10 was associated with AD risk (P < .001). In the combined Asian data sets, SNPs 19 and 23 through 25 were associated withADrisk (P < .001). The disease-associated alleles at SNPs 8, 9, and 10 (120 873 131-120 886 175 base pairs [bp]; C-G-C alleles), at SNP 19 (120 953 300 bp; G allele), and at SNPs 24 through 25 (120 988 611 bp; T and C alleles) were the same previously reported alleles. The SNPs 4 through 5, 8 through 10, 12, and 19 through 25 belong to distinct linkage disequilibrium blocks. The same alleles at SNPs 8 through 10 (C-G-C), 19 (G), and 24 and 25 (T and C) have also been associated with AD endophenotypes, including white matter hyperintensities and hippocampal atrophy on magnetic resonance imaging, cerebrospinal fluid measures of amyloid β-peptide 42, and full-length SORL1 expression in the human brain. Conclusion: This comprehensive meta-analysis provides confirmatory evidence that multiple SORL1 variants in distinct linkage disequilibrium blocks are associated with AD.
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U2 - 10.1001/archneurol.2010.346
DO - 10.1001/archneurol.2010.346
M3 - Article
C2 - 21220680
AN - SCOPUS:78651297619
SN - 0003-9942
VL - 68
SP - 99
EP - 106
JO - Archives of neurology
JF - Archives of neurology
IS - 1
ER -