title: Combined Genome-Wide CSF Aβ-42's Associations and Simple Network Properties Highlight New Risk Factors for Alzheimer's Disease.
abstract: The abnormal deposition of amyloid-β protein in the brain plays an important role in Alzheimer's disease (AD), being considered a potential clinical biomarker. To investigate genetic associations with amyloid-β we used biomarker data and genome-wide variants from individuals with AD and mild cognitive impairment in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We used a standard linear model and retested the associations with a mixed linear model to correct the residual sample structure. Both methods' results showed two identical significant SNPs associated with the A β-42 levels in CSF (rs2075650 at intron region TOMM40 with p-value ≥ 1 × 10-16 and rs439401 in the intergenic region of LOC100129500 and APOC1 with p-value ≥ 1 × 10-9) and highlighted APOC1 and TOMM40, which are well-known genes previously associated with AD. Extending our analysis, we considered possible candidate genes mapped to SNPs with p-value ≥ 1 × 10-6 to explore gene-set enrichment e gene-gene network analysis, which reveals genes related to synaptic transmission, transmission of nerve impulses, cell-cell signaling and neurological processes. These genes require fine mapping and replication studies to allow more detailed understanding of how they may contribute to the genetic architecture of AD.
authors.affiliation: Keizo Asami Laboratory (LIKA), Federal University of Pernambuco (UFPE), Recife, PE, 50670901, Brazil.
authors.forename: M B R
authors.initials: MB
authors.lastname: Souza
authors.affiliation: Center of Informatics, Federal University of Pernambuco (UFPE), Recife, PE, 50670901, Brazil.
authors.forename: G S
authors.initials: GS
authors.lastname: Araújo
authors.affiliation: Center of Informatics, Federal University of Pernambuco (UFPE), Recife, PE, 50670901, Brazil.|Interdiciplinary Center for Clinical Resaarch (IZKF), RWHT Aachen University, Aachen, 52074, Germany.
authors.forename: I G
authors.initials: IG
authors.lastname: Costa
authors.affiliation: Keizo Asami Laboratory (LIKA), Federal University of Pernambuco (UFPE), Recife, PE, 50670901, Brazil. joao.ricardo@ufpe.br.|Department of Neuropsychiatry, Federal University of Pernambuco (UFPE), Av. Prof. Morais Rego, s/n-cidade Universitária, 50670901, Recife, PE, Brazil. joao.ricardo@ufpe.br.
authors.forename: J R M
authors.initials: JR
authors.lastname: Oliveira
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000235:genetics; D053302:Apolipoprotein C-I / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D010446:Peptide Fragments / Q000134:cerebrospinal fluid* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: C505803:APOC1 protein, human; D016229:Amyloid beta-Peptides; D053302:Apolipoprotein C-I; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D010446:Peptide Fragments; C400783:TOMM40 protein, human; C075222:amyloid beta-protein (1-42)
keywords: A β-42; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Alzheimer’s disease; Biomarkers; Mild cognitive impairment