Genome-wide association analysis of age-at-onset in Alzheimer's disease

M. I. Kamboh, M. M. Barmada, F. Y. Demirci, R. L. Minster, M. M. Carrasquillo, V. S. Pankratz, S. G. Younkin, Andrew Saykin, R. A. Sweet, E. Feingold, S. T. Dekosky, O. L. Lopez

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The risk of Alzheimer's disease (AD) is strongly determined by genetic factors and recent genome-wide association studies (GWAS) have identified several genes for the disease risk. In addition to the disease risk, age-at-onset (AAO) of AD has also strong genetic component with an estimated heritability of 42%. Identification of AAO genes may help to understand the biological mechanisms that regulate the onset of the disease. Here we report the first GWAS focused on identifying genes for the AAO of AD. We performed a genome-wide meta-analysis on three samples comprising a total of 2222 AD cases. A total of ∼2.5 million directly genotyped or imputed single-nucleotide polymorphisms (SNPs) were analyzed in relation to AAO of AD. As expected, the most significant associations were observed in the apolipoprotein E (APOE) region on chromosome 19 where several SNPs surpassed the conservative genome-wide significant threshold (P<5E-08). The most significant SNP outside the APOE region was located in the DCHS2 gene on chromosome 4q31.3 (rs1466662; P4.95E-07). There were 19 additional significant SNPs in this region at P<1E-04 and the DCHS2 gene is expressed in the cerebral cortex and thus is a potential candidate for affecting AAO in AD. These findings need to be confirmed in additional well-powered samples.

Original languageEnglish
Pages (from-to)1340-1346
Number of pages7
JournalMolecular Psychiatry
Volume17
Issue number12
DOIs
StatePublished - Dec 2012

Fingerprint

Genome-Wide Association Study
Age of Onset
Alzheimer Disease
Single Nucleotide Polymorphism
Genes
Apolipoproteins E
Genome
Chromosomes, Human, Pair 19
Cerebral Cortex
Meta-Analysis
Chromosomes

Keywords

  • age-at-onset
  • Alzheimer's disease
  • genome-wide association study
  • meta-analysis
  • single-nucleotide polymorphisms

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Kamboh, M. I., Barmada, M. M., Demirci, F. Y., Minster, R. L., Carrasquillo, M. M., Pankratz, V. S., ... Lopez, O. L. (2012). Genome-wide association analysis of age-at-onset in Alzheimer's disease. Molecular Psychiatry, 17(12), 1340-1346. https://doi.org/10.1038/mp.2011.135

Genome-wide association analysis of age-at-onset in Alzheimer's disease. / Kamboh, M. I.; Barmada, M. M.; Demirci, F. Y.; Minster, R. L.; Carrasquillo, M. M.; Pankratz, V. S.; Younkin, S. G.; Saykin, Andrew; Sweet, R. A.; Feingold, E.; Dekosky, S. T.; Lopez, O. L.

In: Molecular Psychiatry, Vol. 17, No. 12, 12.2012, p. 1340-1346.

Research output: Contribution to journalArticle

Kamboh, MI, Barmada, MM, Demirci, FY, Minster, RL, Carrasquillo, MM, Pankratz, VS, Younkin, SG, Saykin, A, Sweet, RA, Feingold, E, Dekosky, ST & Lopez, OL 2012, 'Genome-wide association analysis of age-at-onset in Alzheimer's disease', Molecular Psychiatry, vol. 17, no. 12, pp. 1340-1346. https://doi.org/10.1038/mp.2011.135
Kamboh MI, Barmada MM, Demirci FY, Minster RL, Carrasquillo MM, Pankratz VS et al. Genome-wide association analysis of age-at-onset in Alzheimer's disease. Molecular Psychiatry. 2012 Dec;17(12):1340-1346. https://doi.org/10.1038/mp.2011.135
Kamboh, M. I. ; Barmada, M. M. ; Demirci, F. Y. ; Minster, R. L. ; Carrasquillo, M. M. ; Pankratz, V. S. ; Younkin, S. G. ; Saykin, Andrew ; Sweet, R. A. ; Feingold, E. ; Dekosky, S. T. ; Lopez, O. L. / Genome-wide association analysis of age-at-onset in Alzheimer's disease. In: Molecular Psychiatry. 2012 ; Vol. 17, No. 12. pp. 1340-1346.
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