ArticleAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics2010
Evidence for three loci modifying age-at-onset of Alzheimer's disease in early-onset PSEN2 families.
Article in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Identification of genetic modifiers of autosomal dominant Alzheimer's disease: a genome-wide association study.The Lancet. Neurology · 2026Article
- α5-GABAA Receptor Modulation Reverses Behavioral and Neurophysiological Correlates of Psychosis in Rats with Ventral Hippocampal Alzheimer's Disease-like Pathology.International journal of molecular sciences · 2023Article
- Variants regulating ZBTB4 are associated with age-at-onset of Alzheimer's disease.Genes, brain, and behavior · 2018Article
- Modifier variant of METTL13 suppresses human GAB1-associated profound deafness.The Journal of clinical investigation · 2018Article
- CRISPR/Cas9-Correctable mutation-related molecular and physiological phenotypes in iPSC-derived Alzheimer's PSEN2Acta neuropathologica communications · 2017Article
- The genetic landscape of Alzheimer disease: clinical implications and perspectives.Genetics in medicine : official journal of the American College of Medical Genetics · 2016Review
- Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease.Molecular psychiatry · 2015Article
- Genetic Modifiers of Age at Onset in Carriers of the G206A Mutation in PSEN1 With Familial Alzheimer Disease Among Caribbean Hispanics.JAMA neurology · 2015Article
- Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease.Human genetics · 2013Review
- Genome scan in familial late-onset Alzheimer's disease: a locus on chromosome 6 contributes to age-at-onset.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2013Article
- Exploratory data from complete genomes of familial alzheimer disease age-at-onset outliers.Human mutation · 2012Article
- Genome scan of age-at-onset in the NIMH Alzheimer disease sample uncovers multiple loci, along with evidence of both genetic and sample heterogeneity.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2011Article
- Genome-wide association of familial late-onset Alzheimer's disease replicates BIN1 and CLU and nominates CUGBP2 in interaction with APOE.PLoS genetics · 2011Article
- Genome scan for spelling deficits: effects of verbal IQ on models of transmission and trait gene localization.Behavior genetics · 2011Article
- Estimation and visualization of identity-by-descent within pedigrees simplifies interpretation of complex trait analysis.Human heredity · 2011Article
- Alzheimer's disease phenotypes and genotypes associated with mutations in presenilin 2.Brain : a journal of neurology · 2010Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Families with early-onset Alzheimer's disease (AD) sharing a single PSEN2 mutation exhibit a wide range of age-at-onset, suggesting that modifier loci segregate within these families. While APOE is known to be an age-at-onset modifier, it does not explain all of this variation. We performed a genome scan within nine such families for loci influencing age-at-onset, while simultaneously controlling for variation in the primary PSEN2 mutation (N141I) and APOE. We found significant evidence of linkage between age-at-onset and chromosome 1q23.3 (P < 0.001) when analysis included all families, and to chromosomes 1q23.3 (P < 0.001), 17p13.2 (P = 0.0002), 7q33 (P = 0.017), and 11p14.2 (P = 0.017) in a single large pedigree. Simultaneous analysis of these four chromosomes maintained strong evidence of linkage to chromosomes 1q23.3 and 17p13.2 when all families were analyzed, and to chromosomes 1q23.3, 7q33, and 17p13.2 within the same single pedigree. Inclusion of major gene covariates proved essential to detect these linkage signals, as all linkage signals dissipated when PSEN2 and APOE were excluded from the model. The four chromosomal regions with evidence of linkage all coincide with previous linkage signals, associated SNPs, and/or candidate genes identified in independent AD study populations. This study establishes several candidate regions for further analysis and is consistent with an oligogenic model of AD risk and age-at-onset. More generally, this study also demonstrates the value of searching for modifier loci in existing datasets previously used to identify primary causal variants for complex disease traits.
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