ArticleMolecular psychiatry2013
Pooling/bootstrap-based GWAS (pbGWAS) identifies new loci modifying the age of onset in PSEN1 p.Glu280Ala Alzheimer's disease.
Article in Molecular psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
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- Genetic modifiers of cognitive decline in PSEN1 E280A Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
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- Translational approaches to understanding resilience to Alzheimer's disease.Trends in neurosciences · 2022Review
- d-Amino Acids and pLG72 in Alzheimer's Disease and Schizophrenia.International journal of molecular sciences · 2021Review
- Association between chronic periodontitis and the risk of Alzheimer's disease: combination of text mining and GEO dataset.BMC oral health · 2021Article
- A Comprehensive Machine Learning Framework for the Exact Prediction of the Age of Onset in Familial and Sporadic Alzheimer's Disease.Diagnostics (Basel, Switzerland) · 2021Article
- A multifactorial model of pathology for age of onset heterogeneity in familial Alzheimer's disease.Acta neuropathologica · 2021Article
- Association of Gremlin-2 gene polymorphisms with osteoporosis risk in Chinese postmenopausal women.Bioscience reports · 2020Observational
- Familial Alzheimer's Disease and Recessive Modifiers.Molecular neurobiology · 2020Article
- Recent Consanguinity and Outbred Autozygosity Are Associated With Increased Risk of Late-Onset Alzheimer's Disease.Frontiers in genetics · 2020Article
- Lithium alters expression of RNAs in a type-specific manner in differentiated human neuroblastoma neuronal cultures, including specific genes involved in Alzheimer's disease.Scientific reports · 2019Article
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Authors and funding
20 authors at 7 institutions in 3 countries.
Funding
Abstract
The literature on GWAS (genome-wide association studies) data suggests that very large sample sizes (for example, 50,000 cases and 50,000 controls) may be required to detect significant associations of genomic regions for complex disorders such as Alzheimer's disease (AD). Because of the challenges of obtaining such large cohorts, we describe here a novel sequential strategy that combines pooling of DNA and bootstrapping (pbGWAS) in order to significantly increase the statistical power and exponentially reduce expenses. We applied this method to a very homogeneous sample of patients belonging to a unique and clinically well-characterized multigenerational pedigree with one of the most severe forms of early onset AD, carrying the PSEN1 p.Glu280Ala mutation (often referred to as E280A mutation), which originated as a consequence of a founder effect. In this cohort, we identified novel loci genome-wide significantly associated as modifiers of the age of onset of AD (CD44, rs187116, P=1.29 × 10⁻¹²; NPHP1, rs10173717, P=1.74 × 10⁻¹²; CADPS2, rs3757536, P=1.54 × 10⁻¹⁰; GREM2, rs12129547, P=1.69 × 10⁻¹³, among others) as well as other loci known to be associated with AD. Regions identified by pbGWAS were confirmed by subsequent individual genotyping. The pbGWAS methodology and the genes it targeted could provide important insights in determining the genetic causes of AD and other complex conditions.
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