Skip to main content
Journal cover image

Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease.

Publication ,  Journal Article
Beecham, GW; Martin, ER; Li, Y-J; Slifer, MA; Gilbert, JR; Haines, JL; Pericak-Vance, MA
Published in: Am J Hum Genet
January 2009

Only Apolipoprotein E polymorphisms have been consistently associated with the risk of late-onset Alzheimer disease (LOAD), but they represent only a minority of the underlying genetic effect. To identify additional LOAD risk loci, we performed a genome-wide association study (GWAS) on 492 LOAD cases and 498 cognitive controls using Illumina's HumanHap550 beadchip. An additional 238 cases and 220 controls were used as a validation data set for single-nucleotide polymorphisms (SNPs) that met genome-wide significance. To validate additional associated SNPs (p < 0.0001) and nominally associated candidate genes, we imputed SNPs from our GWAS using a previously published LOAD GWAS(1) and the IMPUTE program. Association testing was performed with the Cochran-Armitage trend test and logistic regression, and genome-wide significance was determined with the False Discovery Rate-Beta Uniform Mixture method. Extensive quality-control methods were performed at both the sample and the SNP level. The GWAS confirmed the known APOE association and identified association with a 12q13 locus at genome-wide significance; the 12q13 locus was confirmed in our validation data set. Four additional highly associated signals (1q42, 4q28, 6q14, 19q13) were replicated with the use of the imputed data set, and six candidate genes had SNPs with nominal association in both the GWAS and the joint imputated data set. These results help to further define the genetic architecture of LOAD.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Am J Hum Genet

DOI

EISSN

1537-6605

Publication Date

January 2009

Volume

84

Issue

1

Start / End Page

35 / 43

Location

United States

Related Subject Headings

  • Risk
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genome, Human
  • Genetics & Heredity
  • Genetic Predisposition to Disease
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Beecham, G. W., Martin, E. R., Li, Y.-J., Slifer, M. A., Gilbert, J. R., Haines, J. L., & Pericak-Vance, M. A. (2009). Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease. Am J Hum Genet, 84(1), 35–43. https://doi.org/10.1016/j.ajhg.2008.12.008
Beecham, Gary W., Eden R. Martin, Yi-Ju Li, Michael A. Slifer, John R. Gilbert, Jonathan L. Haines, and Margaret A. Pericak-Vance. “Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease.Am J Hum Genet 84, no. 1 (January 2009): 35–43. https://doi.org/10.1016/j.ajhg.2008.12.008.
Beecham GW, Martin ER, Li Y-J, Slifer MA, Gilbert JR, Haines JL, et al. Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease. Am J Hum Genet. 2009 Jan;84(1):35–43.
Beecham, Gary W., et al. “Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease.Am J Hum Genet, vol. 84, no. 1, Jan. 2009, pp. 35–43. Pubmed, doi:10.1016/j.ajhg.2008.12.008.
Beecham GW, Martin ER, Li Y-J, Slifer MA, Gilbert JR, Haines JL, Pericak-Vance MA. Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease. Am J Hum Genet. 2009 Jan;84(1):35–43.
Journal cover image

Published In

Am J Hum Genet

DOI

EISSN

1537-6605

Publication Date

January 2009

Volume

84

Issue

1

Start / End Page

35 / 43

Location

United States

Related Subject Headings

  • Risk
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genome, Human
  • Genetics & Heredity
  • Genetic Predisposition to Disease
  • Female