Alzheimer's disease: analyzing the missing heritability.

TitleAlzheimer's disease: analyzing the missing heritability.
Publication TypeJournal Article
Year of Publication2013
AuthorsRidge, PG, Mukherjee, S, Crane, PK, Kauwe, JSK
Corporate AuthorsAlzheimer’s Disease Genetics Consortium
JournalPLoS One
Volume8
Issue11
Paginatione79771
Date Published2013
ISSN1932-6203
KeywordsAge of Onset, Aged, Alzheimer Disease, Apolipoproteins E, Case-Control Studies, Female, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Quantitative Trait Loci
Abstract

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.

DOI10.1371/journal.pone.0079771
Alternate JournalPLoS ONE
PubMed ID24244562
PubMed Central IDPMC3820606
Grant ListK01 AG030514 / AG / NIA NIH HHS / United States
MH60451 / MH / NIMH NIH HHS / United States
P50 AG016574 / AG / NIA NIH HHS / United States
R01 AG040770 / AG / NIA NIH HHS / United States
P50 AG008671 / AG / NIA NIH HHS / United States
P30 AG010129 / AG / NIA NIH HHS / United States
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U01 HG006375 / HG / NHGRI NIH HHS / United States
M01 RR000645 / RR / NCRR NIH HHS / United States
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P50 AG016573 / AG / NIA NIH HHS / United States
P30 AG10133 / AG / NIA NIH HHS / United States
P50 AG005131 / AG / NIA NIH HHS / United States
P30 AG010133 / AG / NIA NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
R01AG042611 / AG / NIA NIH HHS / United States
P50 AG005133 / AG / NIA NIH HHS / United States
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P30 AG010124 / AG / NIA NIH HHS / United States
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/ / Medical Research Council / United Kingdom
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AG05128 / AG / NIA NIH HHS / United States
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UO1 HG004610 / HG / NHGRI NIH HHS / United States
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/ / Canadian Institutes of Health Research / Canada
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