Evidence map›Paper›PMID 41560352›Full record

ArticleHGG advances2026

Application of the STAAR framework in detecting rare variant associations with Alzheimer disease and related dementias: Insights and implications.

Dongyu Wang, Sabrina Abbruzzese, Nancy Heard-Costa, Andy Rampersaud, Eden Martin, Adam Naj, Bilcag Akgun, Brian Kunkle, Sudha Seshadri, Gina Peloso and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in HGG advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Dongyu WangDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
Sabrina AbbruzzeseDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
Nancy Heard-CostaDepartment of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; NHLBI Framingham Heart Study, Framingham, MA 01702, USA.
Andy RampersaudResearch Computing Services, Information Services & Technology, Boston University, Boston, MA 02215, USA.
Eden MartinJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA; The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, USA, Miami, FL 33136, USA.
Adam NajDepartment of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, Philadelphia, PA 19104, USA; Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Bilcag AkgunJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Brian KunkleJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA; The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, USA, Miami, FL 33136, USA.
Sudha SeshadriDepartment of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; NHLBI Framingham Heart Study, Framingham, MA 01702, USA; Glenn Biggs Institute for Alzheimer's Disease and Neurodegenerative Diseases, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
Gina PelosoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
Alzheimer's Disease Neuroimaging Initiative
Alzheimer's Disease Sequencing Project
Anita L DeStefanoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA; Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
Zilin LiSchool of Mathematics and Statistics and KLAS, Northeast Normal University, Changchun, Jilin 130024, China.
Xihao LiDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: xihaoli@unc.edu.
Seung Hoan ChoiDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA. Electronic address: seuchoi@bu.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rare genetic variation is considered a potential source of heritability in individuals with sporadic Alzheimer disease and related dementias (ADRD). The Variant-set test for association using annotation information (STAAR) framework leverages multiple functional annotations of genetic variants and combines association statistics from multiple variant aggregation-based methods, including burden, sequence kernel association test (SKAT), and aggregated Cauchy association test (ACAT-V), into a single measure of significance. Using whole-genome sequencing data from the Alzheimer's Disease Sequencing Project (ADSP), we comprehensively examined the association of rare genetic variation with ADRD in 23,454 individuals (37% individuals affected by ADRD) and with cognitively healthy elder status in 13,292 individuals (13% cognitively healthy elders) from diverse populations via the STAAR framework. We identified several genes significantly associated with ADRD or cognitively healthy status. However, our analysis revealed several limitations within the STAAR framework incorporating ultra-rare variants with dichotomous outcomes. To enhance the robustness of the framework, we proposed several computational refinements, including creating a burden of ultra-rare variants and employing more precise annotations to match the expected mechanism. After implementing the proposed modifications, the association with ADRD for ZNF200 was no longer statistically significant (α = 1 × 10

Indexed as

Alzheimer DiseaseDementiaGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyHumansWhole Genome SequencingAlzheimer disease and related dementiasrare variant analysisSTAAR frameworkstatistical refinement

Identifiers

PMID41560352
PMCPMC12934298

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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.