RT Journal Article
SR Electronic
T1 Genome-wide association study of CSF biomarkers Aβ<sub>1-42</sub>, t-tau, and p-tau<sub>181p</sub> in the ADNI cohort
JF Neurology
JO Neurology
FD Lippincott Williams &amp; Wilkins
SP 69
OP 79
DO 10.1212/WNL.0b013e318204a397
VO 76
IS 1
A1 S. Kim
A1 S. Swaminathan
A1 L. Shen
A1 S.L. Risacher
A1 K. Nho
A1 T. Foroud
A1 L.M. Shaw
A1 J.Q. Trojanowski
A1 S.G. Potkin
A1 M.J. Huentelman
A1 D.W. Craig
A1 B.M. DeChairo
A1 P.S. Aisen
A1 R.C. Petersen
A1 M.W. Weiner
A1 A.J. Saykin
YR 2011
UL http://n.neurology.org/content/76/1/69.abstract
AB 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 &lt; 0.01 (uncorrected p &lt; 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.