ArticleAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics2009
An association analysis of Alzheimer disease candidate genes detects an ancestral risk haplotype clade in ACE and putative multilocus association between ACE, A2M, and LRRTM3.
Article in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.
- Angiotensin-converting enzyme polymorphisms AND Alzheimer's disease susceptibility: An updated meta-analysis.PloS one · 2021Pooled it
- Angiotensin-converting enzyme gene polymorphisms and risk for sporadic Alzheimer's disease: a meta-analysis.Journal of neural transmission (Vienna, Austria : 1996) · 2015Pooled it
- A decade of progress in understanding LRRTM and Slitrk synaptic cell-adhesion molecules.Molecules and cells · 2026Review
- Pharmacogenetic and Association Studies on the Influence of HLA Alleles and Rivastigmine on the Iranian Patients with Late-Onset Alzheimer's Disease.Molecular neurobiology · 2021Article
- Enhanced synaptic plasticity and spatial memory in female but not male FLRT2-haplodeficient mice.Scientific reports · 2018Article
- acn-1, a C. elegans homologue of ACE, genetically interacts with the let-7 microRNA and other heterochronic genes.Cell cycle (Georgetown, Tex.) · 2017Article
- Clearance of cerebral Aβ in Alzheimer's disease: reassessing the role of microglia and monocytes.Cellular and molecular life sciences : CMLS · 2017Review
- Pharmacogenetic Study on the Impact of Rivastigmine Concerning Genetic Variants of A2M and IL-6 Genes on Iranian Alzheimer's Patients.Molecular neurobiology · 2016Article
- Control of neural circuit formation by leucine-rich repeat proteins.Trends in neurosciences · 2014Review
- The Role of the Renin-Angiotensin System in Amyloid Metabolism of Alzheimer's Disease.Acta Cardiologica Sinica · 2014Review
- Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.Molecular psychiatry · 2014Article
- Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects.Neurobiology of aging · 2014Article
- Influence of genetic variation on plasma protein levels in older adults using a multi-analyte panel.PloS one · 2013Article
- LRRTM3 interacts with APP and BACE1 and has variants associating with late-onset Alzheimer's disease (LOAD).PloS one · 2013Article
- The leucine-rich repeat superfamily of synaptic adhesion molecules: LRRTMs and Slitrks.Molecules and cells · 2012Review
- Effect of genetic variation in LRRTM3 on risk of Alzheimer disease.Archives of neurology · 2012Article
- A multi-center study of ACE and the risk of late-onset Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2011Article
- A general framework for formal tests of interaction after exhaustive search methods with applications to MDR and MDR-PDT.PloS one · 2010Article
- A cross-validation procedure for general pedigrees and matched odds ratio fitness metric implemented for the multifactor dimensionality reduction pedigree disequilibrium test.Genetic epidemiology · 2010Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is the most common form of progressive dementia in the elderly. It is a neurodegenerative disorder characterized by the neuropathologic findings of neurofibrillary tangles and amyloid plaques that accumulate in vulnerable brain regions. AD etiology has been studied by many groups, but since the discovery of the APOE epsilon4 allele, no further genes have been mapped conclusively to late-onset AD (LOAD). In this study, we examined genetic association with LOAD susceptibility in 738 Caucasian families (4,704 individuals) and an independent case-control dataset with 296 cases and 566 controls exploring 11 candidate genes (47 SNPs common to both samples). In addition to tests for main effects and haplotypes, the MDR-PDT was used to search for gene-gene interactions in the family data. We observed significant haplotype effects in ACE in family and case-control samples using standard and cladistic haplotype models. ACE was also part of significant 2 and 3-locus MDR-PDT joint effects models with Alpha-2-Macroglobulin (A2M), which mediates the clearance of Abeta, and Leucine-Rich Repeat Transmembrane-3 (LRRTM3), a nested gene in Alpha-3 Catenin (CTNNA3) which binds Presenilin-1. This result did not replicate in the case-control sample, and may not be a true positive. These genes are related to Abeta clearance; thus this constellation of effects might constitute an axis of susceptibility for LOAD. The consistent ACE haplotype result between independent family-based and unrelated case-control datasets is strong evidence in favor of ACE as a susceptibility locus for AD, and replicates results from several other studies in a large sample.
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