ArticleAmerican journal of human genetics2019
A Rare Variant Nonparametric Linkage Method for Nuclear and Extended Pedigrees with Application to Late-Onset Alzheimer Disease via WGS Data.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Systematic review and meta-analysis of the association betweenFrontiers in aging neuroscience · 2024Pooled it
- Structural basis for regulation of the proteasome 20S core particle by the Parkinsonism-associated proteins FBXO7 and PI31.bioRxiv : the preprint server for biology · 2026Article
- Advancements in the Study of Missense Mutations in ABCA7 in Alzheimer's Disease.Journal of molecular neuroscience : MN · 2026Review
- Variants in the proteasome regulator PSMF1 cause a phenotypic spectrum from parkinsonism to perinatal lethality.Nature communications · 2026Article
- Magical moments in protease biology: proteasome autocatalytic activation and PI31-mediated inhibition.Trends in biochemical sciences · 2026Review
- PI31 expression is neuroprotective in a mouse model of early-onset parkinsonism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- RetroFun-RVS: A Retrospective Family-Based Framework for Rare Variant Analysis Incorporating Functional Annotations.Genetic epidemiology · 2025Article
- BICEP: Bayesian inference for rare genomic variant causality evaluation in pedigrees.Briefings in bioinformatics · 2024Article
- The ABC's of Alzheimer risk gene ABCA7.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Rational design of proteasome inhibitors based on the structure of the endogenous inhibitor PI31/Fub1.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The National Institute on Aging Late-Onset Alzheimer's Disease Family Based Study: A resource for genetic discovery.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Yeast PI31 inhibits the proteasome by a direct multisite mechanism.Nature structural & molecular biology · 2022Article
- The role of ATP-binding cassette subfamily A in the etiology of Alzheimer's disease.Molecular neurodegeneration · 2022Review
- Hereditable variants of classical protein tyrosine phosphatase genes: Will they prove innocent or guilty?Frontiers in cell and developmental biology · 2022Review
- Whole-genome sequencing reveals new Alzheimer's disease-associated rare variants in loci related to synaptic function and neuronal development.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- Review
- The Genetics of Alzheimer's Disease in the Chinese Population.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
To analyze family-based whole-genome sequence (WGS) data for complex traits, we developed a rare variant (RV) non-parametric linkage (NPL) analysis method, which has advantages over association methods. The RV-NPL differs from the NPL in that RVs are analyzed, and allele sharing among affected relative-pairs is estimated only for minor alleles. Analyzing families can increase power because causal variants with familial aggregation usually have larger effect sizes than those underlying sporadic diseases. Differing from association analysis, for NPL only affected individuals are analyzed, which can increase power, since unaffected family members can be susceptibility variant carriers. RV-NPL is robust to population substructure and admixture, inclusion of nonpathogenic variants, as well as allelic and locus heterogeneity and can readily be applied outside of coding regions. In contrast to analyzing common variants using NPL, where loci localize to large genomic regions (e.g., >50 Mb), mapped regions are well defined for RV-NPL. Using simulation studies, we demonstrate that RV-NPL is substantially more powerful than applying traditional NPL methods to analyze RVs. The RV-NPL was applied to analyze 107 late-onset Alzheimer disease (LOAD) pedigrees of Caribbean Hispanic and European ancestry with WGS data, and statistically significant linkage (LOD ≥ 3.8) was found with RVs in PSMF1 and PTPN21 which have been shown to be involved in LOAD etiology. Additionally, nominally significant linkage was observed with RVs in ABCA7, ACE, EPHA1, and SORL1, genes that were previously reported to be associated with LOAD. RV-NPL is an ideal method to elucidate the genetic etiology of complex familial diseases.
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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.