TY - JOUR
T1 - Fine mapping of genetic variants in BIN1, CLU, CR1 and PICALM for association with cerebrospinal fluid biomarkers for Alzheimer's disease
AU - Kauwe, John S.K.
AU - Cruchaga, Carlos
AU - Karch, Celeste M.
AU - Sadler, Brooke
AU - Lee, Mo
AU - Mayo, Kevin
AU - Latu, Wayne
AU - Su'a, Manti
AU - Fagan, Anne M.
AU - Holtzman, David M.
AU - Morris, John C.
AU - Goate, Alison M.
PY - 2011
Y1 - 2011
N2 - Recent genome-wide association studies of Alzheimer's disease (AD) have identified variants in BIN1, CLU, CR1 and PICALM that show replicable association with risk for disease. We have thoroughly sampled common variation in these genes, genotyping 355 variants in over 600 individuals for whom measurements of two AD biomarkers, cerebrospinal fluid (CSF) 42 amino acid amyloid beta fragments (Aβ42) and tau phosphorylated at threonine 181 (ptau181), have been obtained. Association analyses were performed to determine whether variants in BIN1, CLU, CR1 or PICALM are associated with changes in the CSF levels of these biomarkers. Despite adequate power to detect effects as small as a 1.05 fold difference, we have failed to detect evidence for association between SNPs in these genes and CSF Aβ42 or ptau181 levels in our sample. Our results suggest that these variants do not affect risk via a mechanism that results in a strong additive effect on CSF levels of Aβ42 or ptau181.
AB - Recent genome-wide association studies of Alzheimer's disease (AD) have identified variants in BIN1, CLU, CR1 and PICALM that show replicable association with risk for disease. We have thoroughly sampled common variation in these genes, genotyping 355 variants in over 600 individuals for whom measurements of two AD biomarkers, cerebrospinal fluid (CSF) 42 amino acid amyloid beta fragments (Aβ42) and tau phosphorylated at threonine 181 (ptau181), have been obtained. Association analyses were performed to determine whether variants in BIN1, CLU, CR1 or PICALM are associated with changes in the CSF levels of these biomarkers. Despite adequate power to detect effects as small as a 1.05 fold difference, we have failed to detect evidence for association between SNPs in these genes and CSF Aβ42 or ptau181 levels in our sample. Our results suggest that these variants do not affect risk via a mechanism that results in a strong additive effect on CSF levels of Aβ42 or ptau181.
UR - http://www.scopus.com/inward/record.url?scp=79951798741&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0015918
DO - 10.1371/journal.pone.0015918
M3 - Article
C2 - 21347408
AN - SCOPUS:79951798741
SN - 1932-6203
VL - 6
JO - PloS one
JF - PloS one
IS - 2
M1 - e15918
ER -