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Evaluation of the Genetic Variance of Alzheimer's Disease Explained by the Disease-Associated Chromosomal Regions.

Publication ,  Journal Article
Nazarian, A; Kulminski, AM
Published in: Journal of Alzheimer's disease : JAD
January 2019

Heritability analysis of complex traits/diseases is commonly performed to obtain illustrative information about the potential contribution of the genetic factors to their phenotypic variances. In this study, we investigated the narrow-sense heritability (h2) of Alzheimer's disease (AD) using genome-wide single-nucleotide polymorphisms (SNPs) data from three independent studies in the linear mixed models framework. Our meta-analyses demonstrated that the estimated h2 values (and their standard errors) of AD in liability scale were 0.280 (0.091), 0.348 (0.113), and 0.389 (0.126) assuming AD prevalence rates of 10%, 20%, or 30% at ages of 65+, 75+, and 85+ years, respectively. We also found that chromosomal regions containing two or more AD-associated SNPs at p < 5E-08 could collectively explain 37% of the additive genetic variance of AD in our samples. AD-associated regions in which at least one SNP had attained p < 5E-08 explained 56% of the additive genetic variance of AD. These regions harbored 3% and 11% of SNPs in our analyses. Also, the chromosomal regions containing two or more and one or more AD-associated SNPs at p < 5E-06 accounted for 72% and 94% of the additive genetic variance of AD, respectively. These regions harbored 27% and 44% of SNPs in our analyses. Our findings showed that the overall contribution of the additive genetic effects to the AD liability was moderate and age-dependent. Also, they supported the importance of focusing on known AD-associated chromosomal regions to investigate the genetic basis of AD, e.g., through haplotype analysis, analysis of heterogeneity, and functional studies.

Duke Scholars

Published In

Journal of Alzheimer's disease : JAD

DOI

EISSN

1875-8908

ISSN

1387-2877

Publication Date

January 2019

Volume

70

Issue

3

Start / End Page

907 / 915

Related Subject Headings

  • United States
  • Polymorphism, Single Nucleotide
  • Neurology & Neurosurgery
  • Multifactorial Inheritance
  • Meta-Analysis as Topic
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation
  • Genetic Predisposition to Disease
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Nazarian, A., & Kulminski, A. M. (2019). Evaluation of the Genetic Variance of Alzheimer's Disease Explained by the Disease-Associated Chromosomal Regions. Journal of Alzheimer’s Disease : JAD, 70(3), 907–915. https://doi.org/10.3233/jad-190168
Nazarian, Alireza, and Alexander M. Kulminski. “Evaluation of the Genetic Variance of Alzheimer's Disease Explained by the Disease-Associated Chromosomal Regions.Journal of Alzheimer’s Disease : JAD 70, no. 3 (January 2019): 907–15. https://doi.org/10.3233/jad-190168.
Nazarian A, Kulminski AM. Evaluation of the Genetic Variance of Alzheimer's Disease Explained by the Disease-Associated Chromosomal Regions. Journal of Alzheimer’s disease : JAD. 2019 Jan;70(3):907–15.
Nazarian, Alireza, and Alexander M. Kulminski. “Evaluation of the Genetic Variance of Alzheimer's Disease Explained by the Disease-Associated Chromosomal Regions.Journal of Alzheimer’s Disease : JAD, vol. 70, no. 3, Jan. 2019, pp. 907–15. Epmc, doi:10.3233/jad-190168.
Nazarian A, Kulminski AM. Evaluation of the Genetic Variance of Alzheimer's Disease Explained by the Disease-Associated Chromosomal Regions. Journal of Alzheimer’s disease : JAD. 2019 Jan;70(3):907–915.

Published In

Journal of Alzheimer's disease : JAD

DOI

EISSN

1875-8908

ISSN

1387-2877

Publication Date

January 2019

Volume

70

Issue

3

Start / End Page

907 / 915

Related Subject Headings

  • United States
  • Polymorphism, Single Nucleotide
  • Neurology & Neurosurgery
  • Multifactorial Inheritance
  • Meta-Analysis as Topic
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation
  • Genetic Predisposition to Disease