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Arch Neurol. 2012 Oct;69(10):1270-9.

Comprehensive search for Alzheimer disease susceptibility loci in the APOE region.

Collaborators (135)

Apostolova LG, Arnold SE, Baldwin CT, Barmada MM, Beach TG, Beecham GW, Beekly D, Bennett DA, Bigio EH, Bird TD, Blacker D, Boeve BF, Bowen JD, Boxer A, Buxbaum JD, Cairns NJ, Cantwell LB, Cao C, Carney RM, Carrasquillo MM, Carroll SL, Corneveaux J, Cotman CW, Crocco EA, Cruchaga C, Cummings JL, De Jager PL, DeCarli C, DeKosky ST, Demirci FY, Diaz-Arrastia R, Dick M, Dickson DW, Duara R, Ellis WG, Ertekin-Taner N, Evans D, Faber KM, Fallon KB, Farlow MR, Ferris S, Foroud TM, Frosch MP, Galasko DR, Ganguli M, Gearing M, Geschwind DH, Ghetti B, Gilbert JR, Gilman S, Giordani B, Glass JD, Goate AM, Graff-Radford NR, Green RC, Hakonarson H, Hamilton RL, Hardy J, Harrell LE, Head E, Honig LS, Huentelman MJ, Hulette CM, Hyman BT, Jarvik GP, Jicha GA, Jin LW, Kamboh MI, Karydas A, Kauwe JS, Kaye JA, Kim R, Kowall NW, Kramer P, Kukull WA, Lah JJ, Levey AI, Lieberman AP, Lopez OL, Mack WJ, Martin ER, Martiniuk F, Mash DC, Masliah E, McCormick WC, McCurry SM, McDavid AN, McKee AC, Mesulam M, Miller BL, Miller CA, Miller JW, Montine TJ, Morris JC, Myers AJ, Naj AC, Nowotny P, Parisi JE, Peskind E, Petersen RC, Poon WW, Potter H, Quinn JF, Raj A, Rajbhandary RA, Raskind M, Reiman EM, Reisberg B, Reitz C, Ringman JM, Roberson ED, Rogaeva E, Rosenberg RN, Sano M, Saykin AJ, Schneider JA, Schneider LS, Seeley WW, Sonnen JA, Spina S, George-Hyslop PS, Stern RA, Tanzi RE, Trojanowski JQ, Troncoso JC, Tsuang DW, Valladares O, Van Deerlin VM, Vinters HV, Vonsattel JP, Wang LS, Weintraub S, Woltjer RL, Wright CB, Younkin SG.

Author information

  • 1Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine and Public Health, Boston, MA, USA.

Abstract

OBJECTIVE:

To evaluate the association of risk and age at onset (AAO) of Alzheimer disease (AD) with single-nucleotide polymorphisms (SNPs) in the chromosome 19 region including apolipoprotein E (APOE) and a repeat-length polymorphism in TOMM40 (poly-T, rs10524523).

DESIGN:

Conditional logistic regression models and survival analysis.

SETTING:

Fifteen genome-wide association study data sets assembled by the Alzheimer's Disease Genetics Consortium.

PARTICIPANTS:

Eleven thousand eight hundred forty AD cases and 10 931 cognitively normal elderly controls.

MAIN OUTCOME MEASURES:

Association of AD risk and AAO with genotyped and imputed SNPs located in an 800-Mb region including APOE in the entire Alzheimer's Disease Genetics Consortium data set and with the TOMM40 poly-T marker genotyped in a subset of 1256 cases and 1605 controls.

RESULTS:

In models adjusting for APOE ε4, no SNPs in the entire region were significantly associated with AAO at P.001. Rs10524523 was not significantly associated with AD or AAO in models adjusting for APOE genotype or within the subset of ε3/ε3 subjects.

CONCLUSIONS:

APOE alleles ε2, ε3, and ε4 account for essentially all the inherited risk of AD associated with this region. Other variants including a poly-T track in TOMM40 are not independent risk or AAO loci.

Comment in

PMID:
22869155
[PubMed - indexed for MEDLINE]
PMCID:
PMC3579659
Free PMC Article

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