Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Feb 9;6(2):e15918.
doi: 10.1371/journal.pone.0015918.

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  1 , 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; Alzheimer's Disease Neuroimaging Initiative; Alison M Goate
Collaborators, Affiliations

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 et al. PLoS One. .

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 (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).

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Similar articles

See all similar articles

Cited by

  • Additional mechanisms conferring genetic susceptibility to Alzheimer's disease.
    Calero M, Gómez-Ramos A, Calero O, Soriano E, Avila J, Medina M. Calero M, et al. Front Cell Neurosci. 2015 Apr 9;9:138. doi: 10.3389/fncel.2015.00138. eCollection 2015. Front Cell Neurosci. 2015. PMID: 25914626 Free PMC article. Review.
  • Relationship between plasma analytes and SPARE-AD defined brain atrophy patterns in ADNI.
    Toledo JB, Da X, Bhatt P, Wolk DA, Arnold SE, Shaw LM, Trojanowski JQ, Davatzikos C; Alzheimer’s Disease Neuroimaging Initiative. Toledo JB, et al. PLoS One. 2013;8(2):e55531. doi: 10.1371/journal.pone.0055531. Epub 2013 Feb 8. PLoS One. 2013. PMID: 23408997 Free PMC article.
  • Alzheimer risk genes modulate the relationship between plasma apoE and cortical PiB binding.
    Lazaris A, Hwang KS, Goukasian N, Ramirez LM, Eastman J, Blanken AE, Teng E, Gylys K, Cole G, Saykin AJ, Shaw LM, Trojanowski JQ, Jagust WJ, Weiner MW, Apostolova LG; Alzheimer's Disease Neuroimaging Initiative. Lazaris A, et al. Neurol Genet. 2015 Oct 15;1(3):e22. doi: 10.1212/NXG.0000000000000022. eCollection 2015 Oct. Neurol Genet. 2015. PMID: 27066559 Free PMC article.
  • GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease.
    Cruchaga C, Kauwe JS, Harari O, Jin SC, Cai Y, Karch CM, Benitez BA, Jeng AT, Skorupa T, Carrell D, Bertelsen S, Bailey M, McKean D, Shulman JM, De Jager PL, Chibnik L, Bennett DA, Arnold SE, Harold D, Sims R, Gerrish A, Williams J, Van Deerlin VM, Lee VM, Shaw LM, Trojanowski JQ, Haines JL, Mayeux R, Pericak-Vance MA, Farrer LA, Schellenberg GD, Peskind ER, Galasko D, Fagan AM, Holtzman DM, Morris JC; GERAD Consortium; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Alzheimer Disease Genetic Consortium (ADGC); Goate AM. Cruchaga C, et al. Neuron. 2013 Apr 24;78(2):256-68. doi: 10.1016/j.neuron.2013.02.026. Epub 2013 Apr 4. Neuron. 2013. PMID: 23562540 Free PMC article.
  • The Mechanistic Role of Bridging Integrator 1 (BIN1) in Alzheimer's Disease.
    Gao P, Ye L, Cheng H, Li H. Gao P, et al. Cell Mol Neurobiol. 2021 Oct;41(7):1431-1440. doi: 10.1007/s10571-020-00926-y. Epub 2020 Jul 27. Cell Mol Neurobiol. 2021. PMID: 32719966 Review.
See all "Cited by" articles

References

    1. Beecham GW, Martin ER, Li YJ, Slifer MA, Gilbert JR, et al. Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease. Am J Hum Genet. 2009;84:35–43. - PMC - PubMed
    1. Bertram L, Lange C, Mullin K, Parkinson M, Hsiao M, et al. Genome-wide association analysis reveals putative Alzheimer's disease susceptibility loci in addition to APOE. Am J Hum Genet. 2008;83:623–632. - PMC - PubMed
    1. Carrasquillo MM, Zou F, Pankratz VS, Wilcox SL, Ma L, et al. Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease. Nat Genet. 2009;41:192–198. - PMC - PubMed
    1. Coon KD, Myers AJ, Craig DW, Webster JA, Pearson JV, et al. A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer's disease. J Clin Psychiatry. 2007;68:613–618. - PubMed
    1. Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet. 2009;41:1088–1093. - PMC - PubMed

Publication types

MeSH terms