Arch Neurol -- Meta-analysis Confirms CR1, CLU, and PICALM as Alzheimer Disease Risk Loci and Reveals Interactions With APOE Genotypes, August 9, 2010, Jun et al. 0 (2010): archneurol.2010.201v1

Meta-analysis Confirms CR1, CLU, and PICALM as Alzheimer Disease Risk Loci and Reveals Interactions With APOE Genotypes
Gyungah Jun, PhD; Adam C. Naj, PhD; Gary W. Beecham, PhD; Li-San Wang, PhD; Jacqueline Buros, BS; Paul J. Gallins, MS; Joseph D. Buxbaum, PhD; Nilufer Ertekin-Taner, MD, PhD; M. Daniele Fallin, PhD; Robert Friedland, MD; Rivka Inzelberg, MD; Patricia Kramer, PhD; Ekaterina Rogaeva, PhD; Peter St. George-Hyslop, MD, FRCP; Laura B. Cantwell, MPH; Beth A. Dombroski, PhD; Andrew J. Saykin, PsyD; Eric M. Reiman, MD; David A. Bennett, MD; John C. Morris, MD; Kathryn L. Lunetta, PhD; Eden R. Martin, PhD; Thomas J. Montine, MD, PhD; Alison M. Goate, DPhil; Deborah Blacker, MD; Debby W. Tsuang, MD; Duane Beekly, BS; L. Adrienne Cupples, PhD; Hakon Hakonarson, MD, PhD; Walter Kukull, PhD; Tatiana M. Foroud, PhD; Jonathan Haines, PhD; Richard Mayeux, MD; Lindsay A. Farrer, PhD; Margaret A. Pericak-Vance, PhD; Gerard D. Schellenberg, PhD; Alzheimer's Disease Genetics Consortium
Arch Neurol. Published online August 9, 2010. doi:10.1001/archneurol.2010.201

ABSTRACT

Objectives
To determine whether genotypes at CLU, PICALM, and CR1 confer risk for Alzheimer disease (AD) and whether risk for AD associated with these genes is influenced by apolipoprotein E (APOE) genotypes.

Design Association study of AD and CLU, PICALM, CR1, and APOE genotypes.

Setting Academic research institutions in the United States, Canada, and Israel.

Participants
Seven thousand seventy cases with AD, 3055 with autopsies, and 8169 elderly cognitively normal controls, 1092 with autopsies, from 12 different studies, including white, African American, Israeli-Arab, and Caribbean Hispanic individuals.

Results
Unadjusted, CLU (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.85-0.96 for single-nucleotide polymorphism [SNP] rs11136000), CR1 (OR, 1.14; 95% CI, 1.07-1.22; SNP rs3818361), and PICALM (OR, 0.89; 95% CI, 0.84-0.94, SNP rs3851179) were associated with AD in white individuals. None were significantly associated with AD in the other ethnic groups. APOE 4 was significantly associated with AD (ORs, 1.80-9.05) in all but 1 small white cohort and in the Arab cohort. Adjusting for age, sex, and the presence of at least 1 APOE 4 allele greatly reduced evidence for association with PICALM but not CR1 or CLU. Models with the main SNP effect, presence or absence of APOE 4, and an interaction term showed significant interaction between presence or absence of APOE 4 and PICALM.

Conclusions
We confirm in a completely independent data set that CR1, CLU, and PICALM are AD susceptibility loci in European ancestry populations. Genotypes at PICALM confer risk predominantly in APOE 4–positive subjects. Thus, APOE and PICALM synergistically interact

full-text here:
Arch Neurol -- Meta-analysis Confirms CR1, CLU, and PICALM as Alzheimer Disease Risk Loci and Reveals Interactions With APOE Genotypes, August 9, 2010, Jun et al. 0 (2010): archneurol.2010.201v1


Archives of Neurology, a monthly peer-reviewed medical journal published by AMA
articles:
Archives of Neurology, a monthly peer-reviewed medical journal published by AMA

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