Fine mapping of genetic variants in BIN1, CLU, CR1 and PICALM for association with cerebrospinal fluid biomarkers for Alzheimer's disease

John S.K. Kauwe, Carlos Cruchaga, Celeste M. Karch, Brooke Sadler, Mo Lee, Kevin Mayo, Wayne Latu, Manti Su'a, Anne M. Fagan, David M. Holtzman, John C. Morris, Alison M. Goate

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere15918
JournalPloS one
Volume6
Issue number2
DOIs
StatePublished - 2011

Fingerprint Dive into the research topics of 'Fine mapping of genetic variants in BIN1, CLU, CR1 and PICALM for association with cerebrospinal fluid biomarkers for Alzheimer's disease'. Together they form a unique fingerprint.

Cite this