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Neurology. 2011 Jan 4;76(1):69-79. doi: 10.1212/WNL.0b013e318204a397. Epub 2010 Dec 1.

Genome-wide association study of CSF biomarkers Abeta1-42, t-tau, and p-tau181p in the ADNI cohort.

Collaborators (199)

Jack CR Jr, Jagust W, Toga AW, Beckett L, Gamst A, Soares H, Green RC, Montine T, Thomas RG, Donohue M, Wlater S, Dale A, Bernstein M, Felmlee J, Fox N, Thompson P, Schuff N, Alexander G, DeCarli C, Bandy D, Chen K, Koeppe RA, Foster N, Reiman EM, Mathis C, Morris J, Cairns NJ, Taylor-Reinwald L, Lee VM, Korecka M, Crawford K, Neu S, Kornak J, Buckholtz N, Kaye J, Dolen S, Quinn J, Schneider L, Pawluczyk S, Spann BM, Brewer J, Vanderswag H, Heidebrink JL, Lord JL, Petersen R, Johnson K, Doody RS, Villanueva-Meyer J, Chowdhury M, Stern Y, Honig LS, Bell KL, Morris JC, Mintun MA, Schneider S, Marson D, Griffith R, Clark D, Grossman H, Tang C, Marzloff G, de Toledo-Morrell L, Shah RC, Duara R, Varon D, Roberts P, Albert MS, Pedroso J, Toroney J, Rusinek H, de Leon MJ, De Santi SM, Doraiswamy PM, Petrella JR, Aiello M, Clark CM, Pham C, Nunez J, Smith CD, Given CA 2nd, Hardy P, Lopez OL, Oakley M, Simpson DM, Ismail MS, Brand C, Richard J, Mulnard RA, Thai G, McAdams-Ortiz C, Diaz-Arrastia R, Martin-Cook K, DeVous M, Levey AI, Lah JJ, Cellar JS, Burns JM, Anderson HS, Laubinger MM, Bartzokis G, Silverman DH, Lu PH, Graff-Radford NR, Parfitt F, Johnson H, Farlow M, Herring S, Hake AM, van Dyck CH, MacAvoy MG, Benincasa AL, Chertkow H, Bergman H, Hosein C, Black S, Graham S, Caldwell C, Hsiung GY, Feldman H, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Wu CK, Johnson N, Mesulam M, Sadowsky C, Martinez W, Villena T, Turner RS, Johnson K, Behan KE, Sperling RA, Rentz DM, Johnson KA, Rosen A, Tinklenberg J, Ashford W, Sabbagh M, Connor D, Jacobson S, Killiany R, Norbash A, Nair A, Obisesan TO, Jayam-Trouth A, Wang P, Lerner A, Hudson L, Ogrocki P, DeCarli C, Fletcher E, Carmichael O, Kittur S, Mirje S, Borrie M, Lee TY, Bartha R, Johnson S, Asthana S, Carlsson CM, Potkin SG, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Hendin BA, Scharre DW, Kataki M, Zimmerman EA, Celmins D, Brown AD, Gandy S, Marenberg ME, Rovner BW, Pearlson G, Blank K, Anderson K, Saykin AJ, Santulli RB, Englert J, Williamson JD, Sink KM, Watkins F, Ott BR, Wu CK, Cohen R, Salloway S, Malloy P, Correia S, Rosen HJ, Miller BL, Mintzer J.

Author information

  • 1Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 950 West Walnut Street, R2 E124, Indianapolis, IN 46202, USA.

Abstract

OBJECTIVES:

CSF levels of Aβ1-42, t-tau, and p-tau181p are potential early diagnostic markers for probable Alzheimer disease (AD). The influence of genetic variation on these markers has been investigated for candidate genes but not on a genome-wide basis. We report a genome-wide association study (GWAS) of CSF biomarkers (Aβ1-42, t-tau, p-tau181p, p-tau181p/Aβ1-42, and t-tau/Aβ1-42).

METHODS:

A total of 374 non-Hispanic Caucasian participants in the Alzheimer's Disease Neuroimaging Initiative cohort with quality-controlled CSF and genotype data were included in this analysis. The main effect of single nucleotide polymorphisms (SNPs) under an additive genetic model was assessed on each of 5 CSF biomarkers. The p values of all SNPs for each CSF biomarker were adjusted for multiple comparisons by the Bonferroni method. We focused on SNPs with corrected p<0.01 (uncorrected p<3.10×10(-8)) and secondarily examined SNPs with uncorrected p values less than 10(-5) to identify potential candidates.

RESULTS:

Four SNPs in the regions of the APOE, LOC100129500, TOMM40, and EPC2 genes reached genome-wide significance for associations with one or more CSF biomarkers. SNPs in CCDC134, ABCG2, SREBF2, and NFATC4, although not reaching genome-wide significance, were identified as potential candidates.

CONCLUSIONS:

In addition to known candidate genes, APOE, TOMM40, and one hypothetical gene LOC100129500 partially overlapping APOE; one novel gene, EPC2, and several other interesting genes were associated with CSF biomarkers that are related to AD. These findings, especially the new EPC2 results, require replication in independent cohorts.

PMID:
21123754
[PubMed - indexed for MEDLINE]
PMCID:
PMC3030225
Free PMC Article
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