Affiliations: Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC, USA
Correspondence:
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Correspondence to: Alireza Nazarian, MD, PhD, and Alexander M. Kulminski, PhD, Duke University, Biodemography of Aging Research Unit, Social Science Research Institute, Erwin Mill Building, 2024 W. Main St., Durham, NC 27705, USA. E-mail: alireza.nazarian@duke.edu. (Alireza Nazarian), E-mail: kulminsk@duke.edu. (Alexander M. Kulminski)
Abstract: 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.
