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 DESIGN: Comprehensive and unbiased meta-analysis of all published and unpublished data from case-control studies for the SORL1 single-nucleotide polymorphisms (SNPs) that had been repeatedly assessed across studies.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 the National 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 with AD risk (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.
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 DESIGN: Comprehensive and unbiased meta-analysis of all published and unpublished data from case-control studies for the SORL1 single-nucleotide polymorphisms (SNPs) that had been repeatedly assessed across studies.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 the National 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 with AD risk (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.
Authors: Ekaterina Rogaeva; Yan Meng; Joseph H Lee; Yongjun Gu; Toshitaka Kawarai; Fanggeng Zou; Taiichi Katayama; Clinton T Baldwin; Rong Cheng; Hiroshi Hasegawa; Fusheng Chen; Nobuto Shibata; Kathryn L Lunetta; Raphaelle Pardossi-Piquard; Christopher Bohm; Yosuke Wakutani; L Adrienne Cupples; Karen T Cuenco; Robert C Green; Lorenzo Pinessi; Innocenzo Rainero; Sandro Sorbi; Amalia Bruni; Ranjan Duara; Robert P Friedland; Rivka Inzelberg; Wolfgang Hampe; Hideaki Bujo; You-Qiang Song; Olav M Andersen; Thomas E Willnow; Neill Graff-Radford; Ronald C Petersen; Dennis Dickson; Sandy D Der; Paul E Fraser; Gerold Schmitt-Ulms; Steven Younkin; Richard Mayeux; Lindsay A Farrer; Peter St George-Hyslop Journal: Nat Genet Date: 2007-01-14 Impact factor: 38.330
Authors: Jennifer A Webster; Amanda J Myers; John V Pearson; David W Craig; Diane Hu-Lince; Keith D Coon; Victoria L Zismann; Thomas Beach; Doris Leung; Leslie Bryden; Rebecca F Halperin; Lauren Marlowe; Mona Kaleem; Matthew J Huentelman; Keta Joshipura; Douglas Walker; Christopher B Heward; Rivka Ravid; Joseph Rogers; Andreas Papassotiropoulos; John Hardy; Eric M Reiman; Dietrich A Stephan Journal: Neurodegener Dis Date: 2007-11-01 Impact factor: 2.977
Authors: Chandra A Reynolds; Mun-Gwan Hong; Ulrika K Eriksson; Kaj Blennow; Boo Johansson; Bo Malmberg; Stig Berg; Margaret Gatz; Nancy L Pedersen; Anna M Bennet; Jonathan A Prince Journal: Neurogenetics Date: 2009-08-04 Impact factor: 2.660
Authors: Fan Liu; M Arfan Ikram; A Cecile J W Janssens; Maaike Schuur; Inge de Koning; Aaron Isaacs; Maksim Struchalin; Andre G Uitterlinden; Johan T den Dunnen; Kristel Sleegers; Karolien Bettens; Christine Van Broeckhoven; John van Swieten; Albert Hofman; Ben A Oostra; Yurii S Aulchenko; Monique M B Breteler; Cornelia M van Duijn Journal: J Alzheimers Dis Date: 2009 Impact factor: 4.472
Authors: Gary W Beecham; Eden R Martin; Yi-Ju Li; Michael A Slifer; John R Gilbert; Jonathan L Haines; Margaret A Pericak-Vance Journal: Am J Hum Genet Date: 2009-01 Impact factor: 11.025
Authors: Karen T Cuenco; Kathryn L Lunetta; Clinton T Baldwin; Ann C McKee; Jianping Guo; L Adrienne Cupples; Robert C Green; Peter H St George-Hyslop; Helena Chui; Charles DeCarli; Lindsay A Farrer Journal: Arch Neurol Date: 2008-12
Authors: Hao Li; Sally Wetten; Li Li; Pamela L St Jean; Ruchi Upmanyu; Linda Surh; David Hosford; Michael R Barnes; James David Briley; Michael Borrie; Natalie Coletta; Richard Delisle; Daniella Dhalla; Margaret G Ehm; Howard H Feldman; Luis Fornazzari; Serge Gauthier; Neil Goodgame; Danilo Guzman; Sandra Hammond; Paul Hollingworth; Ging-Yuek Hsiung; Joan Johnson; Devon D Kelly; Ron Keren; Andrew Kertesz; Karen S King; Simon Lovestone; Inge Loy-English; Paul M Matthews; Michael J Owen; Mary Plumpton; William Pryse-Phillips; Rab K Prinjha; Jill C Richardson; Ann Saunders; Andrew J Slater; Peter H St George-Hyslop; Sandra W Stinnett; Jina E Swartz; Rachel L Taylor; John Wherrett; Julie Williams; David P Yarnall; Rachel A Gibson; Michael C Irizarry; Lefkos T Middleton; Allen D Roses Journal: Arch Neurol Date: 2007-11-12
Authors: Richard Sherva; Clinton T Baldwin; Rivka Inzelberg; Badri Vardarajan; L Adrienne Cupples; Kathryn Lunetta; Abdalla Bowirrat; Adam Naj; Margaret Pericak-Vance; Robert P Friedland; Lindsay A Farrer Journal: J Alzheimers Dis Date: 2011 Impact factor: 4.472