scholarly journals Identification of Novel Candidate Genes for Alzheimer's Disease by Autozygosity Mapping using Genome Wide SNP Data

2011 ◽  
Vol 23 (2) ◽  
pp. 349-359 ◽  
Author(s):  
Richard Sherva ◽  
Clinton T. Baldwin ◽  
Rivka Inzelberg ◽  
Badri Vardarajan ◽  
L. Adrienne Cupples ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Candidate Genes ◽  
Autozygosity Mapping ◽  
Snp Data ◽  
Genome Wide

scholarly journals Genetic data and cognitively defined late-onset Alzheimer’s disease subgroups

2018 ◽  
Vol 25 (11) ◽  
pp. 2942-2951 ◽  
Author(s):  
Shubhabrata Mukherjee ◽  
◽  
Jesse Mez ◽  
Emily H. Trittschuh ◽  
Andrew J. Saykin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Disease Diagnosis ◽  
Single Nucleotide ◽  
Cognitively Normal ◽  
Snp Data ◽  
Genotype Frequencies ◽  
Genome Wide ◽  
Ε4 Allele

Abstract Categorizing people with late-onset Alzheimer’s disease into biologically coherent subgroups is important for personalized medicine. We evaluated data from five studies (total n = 4050, of whom 2431 had genome-wide single-nucleotide polymorphism (SNP) data). We assigned people to cognitively defined subgroups on the basis of relative performance in memory, executive functioning, visuospatial functioning, and language at the time of Alzheimer’s disease diagnosis. We compared genotype frequencies for each subgroup to those from cognitively normal elderly controls. We focused on APOE and on SNPs with p < 10−5 and odds ratios more extreme than those previously reported for Alzheimer’s disease (<0.77 or >1.30). There was substantial variation across studies in the proportions of people in each subgroup. In each study, higher proportions of people with isolated substantial relative memory impairment had ≥1 APOE ε4 allele than any other subgroup (overall p = 1.5 × 10−27). Across subgroups, there were 33 novel suggestive loci across the genome with p < 10−5 and an extreme OR compared to controls, of which none had statistical evidence of heterogeneity and 30 had ORs in the same direction across all datasets. These data support the biological coherence of cognitively defined subgroups and nominate novel genetic loci.

scholarly journals Genetic data and cognitively-defined late-onset Alzheimer’s disease subgroups

2018 ◽  
Author(s):  
Shubhabrata Mukherjee ◽  
Jesse Mez ◽  
Emily Trittschuh ◽  
Andrew J. Saykin ◽  
Laura E. Gibbons ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Disease Diagnosis ◽  
Single Nucleotide ◽  
Total N ◽  
Snp Data ◽  
Genotype Frequencies ◽  
Genome Wide ◽  
E4 Allele

AbstractCategorizing people with late-onset Alzheimer’s disease into biologically coherent subgroups is important for personalized medicine. We evaluated data from five studies (total n=4 050, of whom 2 431 had genome-wide single nucleotide polymorphism (SNP) data). We assigned people to cognitively-defined subgroups on the basis of relative performance in memory, executive functioning, visuospatial functioning, and language at the time of Alzheimer’s disease diagnosis. We compared genotype frequencies for each subgroup to those from cognitively normal elderly controls. We focused on APOE and on SNPs with p<10-5 and odds ratios more extreme than those previously reported for Alzheimer’s disease (<0.77 or >1.30). There was substantial variation across studies in the proportions of people in each subgroup. In each study, higher proportions of people with isolated substantial relative memory impairment had ≥1 APOE e4 allele than any other subgroup (overall p= 1.5 × 10-27). Across subgroups, there were 33 novel suggestive loci across the genome with p<10-5 and an extreme OR compared to controls, of which none had statistical evidence of heterogeneity and 30 had ORs in the same direction across all datasets. These data support the biological coherence of cognitively-defined subgroups and nominate novel genetic loci.

Systematic Analysis of Candidate Genes for Alzheimer's Disease in a French, Genome-Wide Association Study

2010 ◽  
Vol 20 (4) ◽  
pp. 1181-1188 ◽  
Author(s):  
Geoffroy Laumet ◽  
Vincent Chouraki ◽  
Benjamin Grenier-Boley ◽  
Vanessa Legry ◽  
Simon Heath ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Study ◽  
Candidate Genes ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Systematic Analysis ◽  
Genome Wide

P4-120: Investigating psychosis candidate genes in Alzheimer's disease with psychosis using genome-wide association studies

2009 ◽  
Vol 5 (4S_Part_15) ◽  
pp. P466-P467
Author(s):  
Rebecca Sims ◽  
Paul Hollingworth ◽  
Richard Abraham ◽  
Denise Harold ◽  
Peter Holmans ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Candidate Genes ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Genome-wide analysis identifies a novel LINC-PINT splice variant associated with vascular amyloid pathology in Alzheimer’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Joseph S. Reddy ◽  
Mariet Allen ◽  
Charlotte C. G. Ho ◽  
Stephanie R. Oatman ◽  
Özkan İş ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genome Wide Association Study ◽  
Transcriptome Profiling ◽  
Brain Regions ◽  
Common Finding ◽  
Amyloid Angiopathy ◽  
Genome Wide ◽  
A Genome ◽  
Male Sex

AbstractCerebral amyloid angiopathy (CAA) contributes to accelerated cognitive decline in Alzheimer’s disease (AD) dementia and is a common finding at autopsy. The APOEε4 allele and male sex have previously been reported to associate with increased CAA in AD. To inform biomarker and therapeutic target discovery, we aimed to identify additional genetic risk factors and biological pathways involved in this vascular component of AD etiology. We present a genome-wide association study of CAA pathology in AD cases and report sex- and APOE-stratified assessment of this phenotype. Genome-wide genotypes were collected from 853 neuropathology-confirmed AD cases scored for CAA across five brain regions, and imputed to the Haplotype Reference Consortium panel. Key variables and genome-wide genotypes were tested for association with CAA in all individuals and in sex and APOEε4 stratified subsets. Pathway enrichment was run for each of the genetic analyses. Implicated loci were further investigated for functional consequences using brain transcriptome data from 1,186 samples representing seven brain regions profiled as part of the AMP-AD consortium. We confirmed association of male sex, AD neuropathology and APOEε4 with increased CAA, and identified a novel locus, LINC-PINT, associated with lower CAA amongst APOEε4-negative individuals (rs10234094-C, beta = −3.70 [95% CI −0.49—−0.24]; p = 1.63E-08). Transcriptome profiling revealed higher LINC-PINT expression levels in AD cases, and association of rs10234094-C with altered LINC-PINT splicing. Pathway analysis indicates variation in genes involved in neuronal health and function are linked to CAA in AD patients. Further studies in additional and diverse cohorts are needed to assess broader translation of our findings.

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