Fine Mapping of Genetic Variants in BIN1, CLU, CR1 and PICALM for Association with Cerebrospinal Fluid Biomarkers for Alzheimer's Disease

被引：50

作者：

Kauwe, John S. K. ^{[1
]}

Cruchaga, Carlos ^{[2
,4
,5
]}

Karch, Celeste M. ^{[2
,4
]}

Sadler, Brooke ^{[2
]}

Lee, Mo ^{[1
]}

Mayo, Kevin ^{[2
,4
]}

Latu, Wayne ^{[1
]}

Su'a, Manti ^{[1
]}

Fagan, Anne M. ^{[3
,4
,5
]}

Holtzman, David M. ^{[3
,4
,5
]}

Morris, John C. ^{[3
,5
]}

Goate, Alison M. ^{[2
,3
,4
,5
]}

机构：

[1] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA

[2] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Charles F & Joanne Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA

来源：

PLOS ONE | 2011年 / 6卷 / 02期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; AMYLOID-BETA; IDENTIFIES VARIANTS; IN-VIVO; SUSCEPTIBILITY; APOE; DEPOSITION; REVEALS; LOCI;

D O I：

10.1371/journal.pone.0015918

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 (A beta(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 A beta(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 A beta(42) or ptau(181).

引用

页数：5

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