Alzheimer’s Disease: Analyzing the Missing Heritability
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No Canadian affiliation. An affiliation-only frame — the usual design — would never have seen this work. It is one of the works that make the case for inverting the frame.
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
- Teacher spread
- 0.215 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
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.
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The record
- Venue
- PLoS ONE
- Topic
- Alzheimer's disease research and treatments
- Field
- Medicine
- Canadian institutions
- —
- Funders
- National Institute of Neurological Disorders and StrokeNational Human Genome Research InstituteNational Institute of Mental HealthNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchGenentechNational Institutes of HealthMedical Research CouncilHersenstichtingUniversitat de BarcelonaBristol-Myers SquibbNorth Bristol NHS TrustHoward Hughes Medical InstituteEisaiNational Cancer InstituteStichting MS ResearchEli Lilly and CompanyAlzheimer's Research TrustNorthern California Institute for Research and EducationMedpaceNational Center for Research ResourcesF. Hoffmann-La RocheWellcome TrustBrigham Young UniversityGlaxoSmithKlinePfizerNovartisElanNewcastle UniversityOffice of Research and DevelopmentU.S. Department of Veterans AffairsSynarcDana FoundationAlzheimer's AssociationAstraZeneca
- Keywords
- International HapMap ProjectGenome-wide association studySingle-nucleotide polymorphismBiologyGeneticsHeritabilityGenotypingMissing heritability problemGenetic associationApolipoprotein EDiseaseGenotypePhenotypeMedicineGenePathology
- Has abstract in OpenAlex
- yes