Genome-wide association study of CSF biomarkers Aβ1-42, t-tau, and p-tau181p in the ADNI cohort

S. Kim, S. Swaminathan, L. Shen, S. L. Risacher, K. Nho, T. Foroud, L. M. Shaw, J. Q. Trojanowski, S. G. Potkin, M. J. Huentelman, D. W. Craig, B. M. Dechairo, P. S. Aisen, R. C. Petersen, M. W. Weiner, A. J. Saykin

Research output: Contribution to journalArticlepeer-review

144 Scopus citations


Objectives: CSF levels of Aβ1-42, t-tau, and p-tau 181p 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 (1-42, 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 Neuromaging 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 x 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.

Original languageEnglish (US)
Pages (from-to)69-79
Number of pages11
Issue number1
StatePublished - Jan 4 2011

ASJC Scopus subject areas

  • Clinical Neurology


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