Association analysis of rare variants near the APOE region with CSF and neuroimaging biomarkers of Alzheimer's disease

• Published in: BMC medical genomics 2017-05, Vol.10 (Suppl 1), p.29-29, Article 29
• Main Authors: Nho, Kwangsik, Kim, Sungeun, Horgusluoglu, Emrin, Risacher, Shannon L, Shen, Li, Kim, Dokyoon, Lee, Seunggeun, Foroud, Tatiana, Shaw, Leslie M, Trojanowski, John Q, Aisen, Paul S, Petersen, Ronald C, Jack, Jr, Clifford R, Weiner, Michael W, Green, Robert C, Toga, Arthur W, Saykin, Andrew J
• Format: Article
• Language: English
• Subjects: ADNI; Age; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - genetics; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Apolipoprotein E; Apolipoproteins; Apolipoproteins E - genetics; Association analysis; Biomarkers; Blood; Blood-brain barrier; Care and treatment; Cerebrospinal fluid; Chromosome 19; Chromosomes; Chromosomes, Human, Pair 19 - genetics; Colony-stimulating factor; Cortex (entorhinal); Cortex (frontal); CSF; Development and progression; Disease; DNA sequencing; Female; Frontal lobe; Gene expression; Gene frequency; Genetic aspects; Genetic variation; Genomes; Health aspects; Heritability; Humans; Magnetic resonance imaging; Male; Medical imaging; Near APOE; Neurodegenerative diseases; Neuroimaging; Nucleotide sequence; Older people; Pathogenesis; Peptide Fragments - cerebrospinal fluid; Polymorphism, Single Nucleotide; Positron emission tomography; Rare variants; RelB protein; Software; Studies; Temporal cortex; Temporal lobe; Transcription; Whole Genome Sequencing; β-Amyloid
• ISSN: 1755-8794; 1755-8794
• DOI: 10.1186/s12920-017-0267-0

The APOE ε4 allele is the most significant common genetic risk factor for late-onset Alzheimer's disease (LOAD). The region surrounding APOE on chromosome 19 has also shown consistent association with LOAD. However, no common variants in the region remain significant after adjusting for APOE genotype. We report a rare variant association analysis of genes in the vicinity of APOE with cerebrospinal fluid (CSF) and neuroimaging biomarkers of LOAD. Whole genome sequencing (WGS) was performed on 817 blood DNA samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Sequence data from 757 non-Hispanic Caucasian participants was used in the present analysis. We extracted all rare variants (MAF (minor allele frequency)