Olfactory receptor copy number association with age at onset of alzheimer disease

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is a devastating neurodegenerative disorder affecting approximately four million individuals in the US and is the most common cause of dementia in North America and Europe. Genetic factors play an important role in the pathogenesis of AD. Heritability is estimated between 58 and 79% based on twin studies, including a large twin study from the Swedish Twin Registry. Our long term goal is to identify genetic variants that may serve as biomarkers for early diagnosis and/or may suggest novel targets for therapeutic intervention. Recently copy number variants (CNVs) have been recognized as important mechanisms of genetic variation contributing to disease phenotypes. In a cases-only genome-wide CNV association study looking for loci affecting AAO of AD we have identified a chromosomal segment on 14q11.2 (reference sequence position 19.3-19.5 Mb) where gene dosage is associated with AAO of AD (genome-wide adjusted p