Evaluation of the Genetic Variance of Alzheimer's Disease Explained by the Disease-Associated Chromosomal Regions.
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.
Nazarian, A; Kulminski, AM
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