ArticleTranslational psychiatry2013
Independent and epistatic effects of variants in VPS10-d receptors on Alzheimer disease risk and processing of the amyloid precursor protein (APP).
Article in Translational psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Multi-trait analysis for genome-wide association study of five psychiatric disorders.Translational psychiatry · 2020Pooled it
- p75 neurotrophin receptor modulation in mild to moderate Alzheimer disease: a randomized, placebo-controlled phase 2a trial.Nature medicine · 2024Trial
- A low frequency damaging SORCS2 variant identified in a family with ADHD compromises receptor stability and quenches activity.Molecular psychiatry · 2026Article
- Spatiotemporal patterns of gene expression changes in the mouse dentate gyrus following entorhinal denervation.Frontiers in molecular neuroscience · 2026Article
- Astrocytes distress triggers brain pathology through induction of δ secretase in a murine model of Alzheimer's disease.Nature communications · 2025Article
- Article
- A triple serine motif in the intracellular domain of SorCS2 impacts its cellular signaling.iScience · 2025Article
- Debiased machine learning for ultra-high dimensional mediation analysis.Bioinformatics (Oxford, England) · 2025Article
- Whole-genome sequencing study in Koreans identifies novel loci for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
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- Genome-wide association study of brain arteriolosclerosis.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Retromer dysfunction in amyotrophic lateral sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Alzheimer Disease: Recent Updates on Apolipoprotein E and Gut Microbiome Mediation of Oxidative Stress, and Prospective Interventional Agents.Aging and disease · 2022Review
- Impact of Genetic Risk Factors for Alzheimer's Disease on Brain Glucose Metabolism.Molecular neurobiology · 2021Review
- Non-coding variants in MYH11, FZD3, and SORCS3 are associated with dementia in women.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- Urinary metabolic phenotyping for Alzheimer's disease.Scientific reports · 2020Article
- Integrated analysis and network pharmacology approaches to explore key genes of Xingnaojing for treatment of Alzheimer's disease.Brain and behavior · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
Genetic variants in the sortilin-related receptor (SORL1) and the sortilin-related vacuolar protein sorting 10 (VPS10) domain-containing receptor 1 (SORCS1) are associated with increased risk of Alzheimer's disease (AD), declining cognitive function and altered amyloid precursor protein (APP) processing. We explored whether other members of the (VPS10) domain-containing receptor protein family (the sortilin-related VPS10 domain-containing receptors 2 and 3 (SORCS2 and SORCS3) and sortilin (SORT1)) would have similar effects either independently or together. We conducted the analyses in a large Caucasian case control data set (n=11,840 cases, 10,931 controls) to determine the associations between single nucleotide polymorphisms (SNPs) in all the five homologous genes and AD risk. Evidence for interactions between SNPs in the five VPS10 domain receptor family genes was determined in epistatic statistical models. We also compared expression levels of SORCS2, SORCS3 and SORT1 in AD and control brains using microarray gene expression analyses and assessed the effects of these genes on γ-secretase processing of APP. Several SNPs in SORL1, SORCS1, SORCS2 and SORCS3 were associated with AD. In addition, four specific linkage disequilibrium blocks in SORCS1, SORCS2 and SORCS3 showed additive epistatic effects on the risk of AD (P≤0.0006). SORCS3, but not SORCS2 or SORT1, showed reduced expression in AD compared with control brains, but knockdown of all the three genes using short hairpin RNAs in HEK293 cells caused a significant threefold increase in APP processing (from P<0.001 to P<0.05). These findings indicate that in addition to SORL1 and SORCS1, variants in other members of the VPS10 domain receptor family (that is, SORCS1, SORCS2, SORCS3) are associated with AD risk and alter APP processing. More importantly, the results indicate that variants within these genes have epistatic effects on AD risk.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.