KIAA1462, A Coronary Artery Disease Associated Gene, Is a Candidate Gene for Late Onset Alzheimer Disease in APOE Carriers

Alzheimer disease (AD) is a devastating neurodegenerative disease affecting more than five million Americans. In this study, we have used updated genetic linkage data from chromosome 10 in combination with expression data from serial analysis of gene expression to choose a new set of thirteen candidate genes for genetic analysis in late onset Alzheimer disease (LOAD). Results in this study identify the KIAA1462 locus as a candidate locus for LOAD in APOE4 carriers. Two genes exist at this locus, KIAA1462, a gene associated with coronary artery disease, and “rokimi”, encoding an untranslated spliced RNA The genetic architecture at this locus suggests that the gene product important in this association is either “rokimi”, or a different isoform of KIAA1462 than the isoform that is important in cardiovascular disease. Expression data suggests that isoform f of KIAA1462 is a more attractive candidate for association with LOAD in APOE4 carriers than “rokimi” which had no detectable expression in brain.

[1]  Mark T. W. Ebbert,et al.  Genetics of Alzheimer's Disease , 2013, BioMed research international.

[2]  T. Komori,et al.  A coronary artery disease-associated gene product, JCAD/KIAA1462, is a novel component of endothelial cell-cell junctions. , 2011, Biochemical and biophysical research communications.

[3]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease: Report of the NINCDS—ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease , 2011, Neurology.

[4]  D. G. Clark,et al.  Common variants in MS4A4/MS4A6E, CD2uAP, CD33, and EPHA1 are associated with late-onset Alzheimer’s disease , 2011, Nature Genetics.

[5]  Mark I. McCarthy,et al.  A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease , 2011, Nature Genetics.

[6]  N. Pedersen,et al.  Nonstroke Cardiovascular Disease and Risk of Alzheimer Disease and Dementia , 2010, Alzheimer disease and associated disorders.

[7]  J. Viña,et al.  Why women have more Alzheimer's disease than men: gender and mitochondrial toxicity of amyloid-beta peptide. , 2010, Journal of Alzheimer's disease : JAD.

[8]  S. DeKosky,et al.  Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease , 2009, Molecular Psychiatry.

[9]  Eleanor Feingold,et al.  Genetic Analysis of Variation in Human Meiotic Recombination , 2009, PLoS genetics.

[10]  Stephan Züchner,et al.  Genomic convergence to identify candidate genes for Alzheimer Disease on chromosome 10 , 2009, Human mutation.

[11]  M. Stephens,et al.  High-Resolution Mapping of Expression-QTLs Yields Insight into Human Gene Regulation , 2008, PLoS genetics.

[12]  J. Gilbert,et al.  A SAGE study of apolipoprotein E3/3, E3/4 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease , 2007, Molecular and Cellular Neuroscience.

[13]  J. Gilbert,et al.  Effect of heterogeneity on the chromosome 10 risk in late‐onset Alzheimer disease , 2007, Human mutation.

[14]  J. Danesh,et al.  Association of apolipoprotein E genotypes with lipid levels and coronary risk. , 2007, JAMA.

[15]  J. Gilbert,et al.  No Association between SNP rs498055 on Chromosome 10 and Late‐Onset Alzheimer Disease in Multiple Datasets , 2007, Annals of human genetics.

[16]  M. Pericak-Vance,et al.  A comparative analysis of the information content in long and short SAGE libraries , 2006, BMC Bioinformatics.

[17]  R. Mahley,et al.  Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[18]  M. Daly,et al.  Haploview: analysis and visualization of LD and haplotype maps , 2005, Bioinform..

[19]  Meir J Stampfer,et al.  Meta-Analysis: Apolipoprotein E Genotypes and Risk for Coronary Heart Disease , 2004, Annals of Internal Medicine.

[20]  Eric J Topol,et al.  Convergence of atherosclerosis and Alzheimer's disease: inflammation, cholesterol, and misfolded proteins , 2004, The Lancet.

[21]  E R Martin,et al.  Genotype‐based association test for general pedigrees: The genotype‐PDT , 2003, Genetic epidemiology.

[22]  Eden R Martin,et al.  Accounting for linkage in family-based tests of association with missing parental genotypes. , 2003, American journal of human genetics.

[23]  D. Bennett,et al.  Alzheimer disease in the US population: prevalence estimates using the 2000 census. , 2003, Archives of neurology.

[24]  L. Farrer,et al.  Identification of multiple loci for Alzheimer disease in a consanguineous Israeli-Arab community. , 2003, Human molecular genetics.

[25]  Tom H. Pringle,et al.  The human genome browser at UCSC. , 2002, Genome research.

[26]  Ji Huang,et al.  [Serial analysis of gene expression]. , 2002, Yi chuan = Hereditas.

[27]  L. Beckett,et al.  Annual Incidence of Alzheimer Disease in the United States Projected to the Years 2000 Through 2050 , 2001, Alzheimer disease and associated disorders.

[28]  J. Blangero,et al.  Linkage of plasma Abeta42 to a quantitative locus on chromosome 10 in late-onset Alzheimer's disease pedigrees. , 2000, Science.

[29]  M G McInnis,et al.  Evidence for genetic linkage of Alzheimer's disease to chromosome 10q. , 2000, Science.

[30]  M. Owen,et al.  Susceptibility locus for Alzheimer's disease on chromosome 10. , 2000, Science.

[31]  P. M. Conneally,et al.  Identification of Novel Genes in Late-Onset Alzheimer's Disease , 2000, Experimental Gerontology.

[32]  E. Martin,et al.  A test for linkage and association in general pedigrees: the pedigree disequilibrium test. , 2000, American journal of human genetics.

[33]  J. Ott,et al.  Heterogeneity for Multiple Disease Loci in Linkage Analysis , 1999, Human Heredity.

[34]  M. Owen,et al.  A full genome scan for late onset Alzheimer's disease , 1999 .

[35]  G. Zubenko,et al.  A genome survey for novel Alzheimer disease risk loci: results at 10-cM resolution. , 1998, Genomics.

[36]  P E Fraser,et al.  Analysis of the 5' sequence, genomic structure, and alternative splicing of the presenilin-1 gene (PSEN1) associated with early onset Alzheimer disease. , 1997, Genomics.

[37]  K. Engedal,et al.  The role of heredity in late-onset Alzheimer disease and vascular dementia. A twin study. , 1997, Archives of general psychiatry.

[38]  J. Rommens,et al.  Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene , 1995, Nature.

[39]  E M Wijsman,et al.  A familial Alzheimer's disease locus on chromosome 1 , 1995, Science.

[40]  S. Hodge What association analysis can and cannot tell us about the genetics of complex disease. , 1994, American journal of medical genetics.

[41]  J. Haines,et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. , 1993, Science.

[42]  M. Pericak-Vance,et al.  Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease , 1991, Nature.

[43]  C. Gieger,et al.  Genome-wide association study identifies a new locus for coronary artery disease on chromosome 10p11.23. , 2011, European heart journal.

[44]  M. Albert,et al.  Results of a high-resolution genome screen of 437 Alzheimer's disease families. , 2003, Human molecular genetics.