Alzheimer's disease: analyzing the missing heritability

Alzheimer's disease (AD) is a complex disorder influenced by environmental and genetic factors. Recent work has identified 11 AD markers in 10 loci. We used Genome-wide Complex Trait Analysis to analyze >2 million SNPs for 10,922 individuals from the Alzheimer's Disease Genetics Consort...

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Bibliographic Details
Published in:PloS one 2013-11, Vol.8 (11), p.e79771-e79771
Main Authors: Ridge, Perry G, Mukherjee, Shubhabrata, Crane, Paul K, Kauwe, John S K
Format: Article
Language:English
Subjects:
Age
Age of Onset
Aged
Alzheimer Disease - genetics
Alzheimer Disease - pathology
Alzheimer's disease
Analysis
Apolipoprotein E
Apolipoproteins
Apolipoproteins E - genetics
Bipolar disorder
Case-Control Studies
Chromosomes
Consortia
Datasets
Estimates
Female
Genes
Genetic aspects
Genetic factors
Genetic Markers
Genetic Predisposition to Disease
Genetics
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genomics
Genotypes
Genotyping
Heritability
Humans
Loci
Male
Markers
Medical research
Polymorphism, Single Nucleotide
Population
Quantitative Trait Loci
Single-nucleotide polymorphism
Studies
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Summary:Alzheimer's disease (AD) is a complex disorder influenced by environmental and genetic factors. Recent work has identified 11 AD markers in 10 loci. We used Genome-wide Complex Trait Analysis to analyze >2 million SNPs for 10,922 individuals from the Alzheimer's Disease Genetics Consortium to assess the phenotypic variance explained first by known late-onset AD loci, and then by all SNPs in the Alzheimer's Disease Genetics Consortium dataset. In all, 33% of total phenotypic variance is explained by all common SNPs. APOE alone explained 6% and other known markers 2%, meaning more than 25% of phenotypic variance remains unexplained by known markers, but is tagged by common SNPs included on genotyping arrays or imputed with HapMap genotypes. Novel AD markers that explain large amounts of phenotypic variance are likely to be rare and unidentifiable using genome-wide association studies. Based on our findings and the current direction of human genetics research, we suggest specific study designs for future studies to identify the remaining heritability of Alzheimer's disease.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0079771