TY - JOUR
T1 - Genome-wide association study of CSF biomarkers Aβ1-42, t-tau, and p-tau181p in the ADNI cohort
AU - Kim, S.
AU - Swaminathan, S.
AU - Shen, L.
AU - Risacher, S. L.
AU - Nho, K.
AU - Foroud, T.
AU - Shaw, L. M.
AU - Trojanowski, J. Q.
AU - Potkin, S. G.
AU - Huentelman, M. J.
AU - Craig, D. W.
AU - Dechairo, B. M.
AU - Aisen, P. S.
AU - Petersen, R. C.
AU - Weiner, M. W.
AU - Saykin, A. J.
N1 - Funding Information:
Study funding: Supported by the NIH (AG024904, AG010129, AG030514, and AG032984) , the Dana Foundation, and the Alzheimer's Disease Genetics Consortium. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH U01 AG024904) .
PY - 2011/1/4
Y1 - 2011/1/4
N2 - 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.
AB - 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.
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U2 - 10.1212/WNL.0b013e318204a397
DO - 10.1212/WNL.0b013e318204a397
M3 - Article
C2 - 21123754
AN - SCOPUS:78751635081
SN - 0028-3878
VL - 76
SP - 69
EP - 79
JO - Neurology
JF - Neurology
IS - 1
ER -