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.
AU - AUTHOR GROUP
AU - Saradha, A.
AU - Abdi, Hervé
AU - Abeliovich, Asa
AU - Abellan van Kan, Gabor
AU - Abner, Erin
AU - Acharya, Deepa
AU - Adams, Nicholas
AU - Adler, Daniel
AU - Agrusti, Antonella
AU - Agyemang, Alex
AU - Ahdidan, Jamila
AU - Ahn, Jae Eun
AU - Aisen, Paul
AU - Aksu, Yaman
AU - Al-Akhras, Mousa
AU - Alarcon, Marcelo
AU - Alberca, Roman
AU - Alexander, Gene
AU - Alexander, Daniel
AU - Almeida, Fabio
AU - Amlien, Inge
AU - Anand, Shyam
AU - Andrew, Marilee
AU - Angersbach, Steve
AU - Anjum, Ayesha
AU - Aoyama, Eiji
AU - Arfanakis, Konstantinos
AU - Armor, Tom
AU - Arnold, Steven
AU - Asatryan, Albert
AU - Ashe-McNalley, Cody
AU - Ashiga, Hirokazu
AU - Assareh, Arezoo
AU - Le Page, Aurelie
AU - Avants, Brian
AU - Avinash, Gopal
AU - Chen, Wei
AU - Schmand, Ben
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 (Aβ(42)) and tau phosphorylated at threonine 181 (ptau(181)), 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 Aβ(42) or ptau(181) 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 Aβ(42) or ptau(181)
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 (Aβ(42)) and tau phosphorylated at threonine 181 (ptau(181)), 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 Aβ(42) or ptau(181) 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 Aβ(42) or ptau(181)
U2 - 10.1371/journal.pone.0015918
DO - 10.1371/journal.pone.0015918
M3 - Article
C2 - 21347408
SN - 1932-6203
VL - 6
SP - e15918
JO - PLoS ONE
JF - PLoS ONE
IS - 2
ER -