Genome-wide association study

Phenotype

DNA repair

Pathology

Neuroscience

Disease

Imputation (statistics)

Biology

Missing data

Gene

Genotype

Machine learning

Genetic association

Single-nucleotide polymorphism

Huntington's disease

PMS2

Computer science

Computational biology

Genetics

DNA mismatch repair

Medicine

Locus (genetics)

The American Journal of Human Genetics

Genome-wide association studies (GWASs) of Huntington disease (HD) have identified six DNA maintenance gene loci (among others) as modifiers and implicated a two step-mechanism of pathogenesis: somatic instability of the causative HTT CAG repeat with subsequent triggering of neuronal damage. The largest studies have been limited to HD individuals with a rater-estimated age at motor onset. To capitalize on the wealth of phenotypic data in several large HD natural history studies, we have performed algorithmic prediction by using common motor and cognitive measures to predict age at other disease landmarks as additional phenotypes for GWASs.

Genetic modifiers of Huntington disease differentially influence motor and cognitive domains