Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database

  title={Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database},
  author={Lars Bertram and Matthew B. McQueen and Kristina Mullin and Deborah Blacker and Rudolph E. Tanzi},
  journal={Nature Genetics},
The past decade has witnessed hundreds of reports declaring or refuting genetic association with putative Alzheimer disease susceptibility genes. This wealth of information has become increasingly difficult to follow, much less interpret. We have created a publicly available, continuously updated database that comprehensively catalogs all genetic association studies in the field of Alzheimer disease ( We performed systematic meta-analyses for each polymorphism with… 
Whole genome association analysis shows that ACE is a risk factor for Alzheimer's disease and fails to replicate most candidates from Meta-analysis.
The results of the ACE replication study are presented with a discussion of the statistical limitations of multiple test corrections in whole genome studies.
Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database
The SzGene project represents the first comprehensive online resource for systematically synthesized and graded evidence of genetic association studies in schizophrenia and could serve as a model for field synopses of genetic associations in other common and genetically complex disorders.
Genome-wide association studies in Alzheimer disease.
This review considers recent publications from studies that have successfully applied genome-wide association methods to investigations of AD by taking advantage of the currently available high-throughput arrays, bioinformatics, and software advances.
Assessment of Alzheimer’s disease case–control associations using family-based methods
The convergence of case–control and family-based findings suggests that these loci currently represent the most promising AD gene candidates and further fine-mapping and functional analyses are warranted to elucidate the potential biochemical mechanisms and epidemiological relevance of these genes.
Genetics of Late-Onset Alzheimer's Disease: Update from the Alzgene Database and Analysis of Shared Pathways
A systematic analysis of gene ontology terms associated with each marker showed that most genes were implicated in cholesterol metabolism, intracellular transport of beta-amyloid precursor, and autophagy of damaged organelles in late-onset Alzheimer's disease.
Gene-Based Rare Allele Analysis Identified a Risk Gene of Alzheimer’s Disease
It is identified that rare variants in ZNF628 are associated with AD, and the associations of APOE and TREM2 with AD were highly significant, even in gene-based rare allele analysis, which implies that further deep sequencing of these genes is required in AD heritability studies.
Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease.
Systematic analysis of candidate genes for Alzheimer's disease in a French, genome-wide association study.
Of the genes showing nominal association with risk of developing Alzheimer's disease in cohorts, TFAM and CHRNB2 appear particularly interesting and warrant further genetic and functional follow-up analyses.
Effect of heterogeneity on the chromosome 10 risk in late‐onset Alzheimer disease
These data continue to support a role for chromosome 10 loci in AD, however, the candidate gene and linkage analysis results did not converge, suggesting that there is more extensive heterogeneity on chromosome 10 than previously appreciated.


Large meta-analysis establishes the ACE insertion-deletion polymorphism as a marker of Alzheimer's disease.
The association of the angiotensin I-converting enzyme indel with Alzheimer's disease across diverse populations is confirmed, although this is probably due to linkage disequilibrium with the true risk factor.
Alzheimer's disease: one disorder, too many genes?
It is suggested that it may be prudent for investigators to pay closer attention to issues such as power, replicability and haplotype structure prior to initial publication to greatly decrease the likelihood of false positive and false negative findings reported in future years.
APOE promoter polymorphisms do not confer independent risk for Alzheimer's disease in a French population
This study does not reinforce the hypothesis of an independent involvement of the APOE promoter region polymorphisms in AD risk, and retested association after adjustment on apoE status and found that the sole association which remained significant was the association with the –427 T allele.
Is M129V of PRNP gene associated with Alzheimer's disease? A case-control study and a meta-analysis
Genomic epidemiology of complex disease: the need for an electronic evidence-based approach to research synthesis.
  • M. Bracken
  • Biology
    American journal of epidemiology
  • 2005
The author proposes that electronic evidence-based methodology, perhaps modeled after that used by the Cochrane Collaboration in clinical medicine, would facilitate the systematic preparation and frequent updating of systematic reviews, which is essential for identifying valid and replicable gene-disease associations.
Association between the interleukin-1alpha gene and Alzheimer's disease: a meta-analysis.
The data support a significant but modest association between the T/T genotype of the IL-1alpha gene and AD and analysis of subgroups showed a significant association in patients with early-onset AD but not in late-onsets AD.
Case-control study of presenilin-1 intronic polymorphism in sporadic early and late onset Alzheimer’s disease
A subtle but positive association of presenilin-1 gene polymorphism with Alzheimer’s disease is suggested, although Japanese data in this study which failed to support such a relation would indicate an ethnic variation.
A genetic dichotomy model for the inheritance of Alzheimer's disease and common age-related disorders.
  • R. Tanzi
  • Biology, Medicine
    The Journal of clinical investigation
  • 1999
There is an emerging consensus that AD is a complex and genetically heterogeneous disorder that is best explained by an age-dependent dichotomous model.