Evidence map›Paper›PMID 42066773›Full record

ArticleAmerican journal of human genetics2026

Multi-ancestry transcriptome-wide association study reveals shared and population-specific genetic effects in Alzheimer disease.

Xinyu Sun, Makaela Mews, Nicholas R Wheeler, Penelope Benchek, Tianjie Gu, Lissette Gomez, Nicholas Ray, Christiane Reitz, Adam C Naj, Jennifer Elizabeth Below and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 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

5 · Who and what money

Authors and funding

21 authors.

Xinyu SunDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
Makaela MewsSystem Biology & Bioinformatics, Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
Nicholas R WheelerDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
Penelope BenchekDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
Tianjie GuJohn P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Lissette GomezJohn P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Nicholas RayTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY, USA.
Christiane ReitzTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY, USA.
Adam C NajDepartment of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jennifer Elizabeth BelowVanderbilt University Medical Center, Nashville, TN, USA.
Giuseppe TostoTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY, USA.
Mario Cornejo-OlivasNeurogenetics Working Group, Universidad Cientifica del Sur, Lima, Peru; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru.
Goldie S ByrdMaya Angelou Center for Health Equity, Wake Forest University, Winston-Salem, NC, USA.
Briseida E Feliciano-AstacioUniversidad Central del Caribe, Bayamón, Puerto Rico.
Katrina CelisJohn P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Farid RajabliJohn P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Brian W KunkleJohn P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Margaret A Pericak-VanceJohn P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Jonathan L HainesDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
Anthony J GriswoldJohn P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
William S BushDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA. Electronic address: wsb36@case.edu.

Funding

Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the ADSP (READD-ADSP)U19AG074865 · NIA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI GOLDIE S. BYRD, William S Bush · 2022 to 2026
$55.3M
Functional genetic analyses of existing data resources to expand AD gene discoveryRF1AG061351 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BELOW, JENNIFER, BUSH, WILLIAM S · 2019 to 2019
$3.0M
Genomic, Epigenomic, and Transcriptomic Mechanisms of Contributing to Alzheimer's Disease Risk in Diverse Ancestral PopulationsRF1AG070935 · NIA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BUSH, WILLIAM S, GRISWOLD, ANTHONY JOHN · 2021 to 2021
$2.3M
Genomic, Epigenomic, and Transcriptomic Mechanisms of Contributing to Alzheimer's Disease Risk in Diverse Ancestral PopulationsR01AG070935 · NIA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BUSH, WILLIAM S, GRISWOLD, ANTHONY JOHN · 2024 to 2025
$1.5M
NIA NIH HHS R01 AG070935NIA NIH HHS RF1 AG061351NIA NIH HHS RF1 AG070935NIA NIH HHS U19 AG074865
6 · The paper itself

Abstract

Alzheimer disease (AD) risk differs across ancestral populations, yet most genetic studies have focused on non-Hispanic White (NHW) cohorts. We conducted a multi-population transcriptome-wide association study (TWAS) using whole-blood RNA sequencing (RNA-seq) and genotype data from NHW (n = 235), African American (AA; n = 224), and Hispanic (HISP; n = 292) Multi-Ancestry Genomics, Epigenomics, and Transcriptomics of Alzheimer's (MAGENTA) participants. Using sum of shared single effects (SuShiE) for multi-population cis-eQTL fine-mapping, we identified credible sets for 8,748 genes, improving fine-mapping precision relative to analyses using fewer populations. cis-eQTL effects were largely shared across populations, with a subset showing population-specific regulation. We performed population-stratified TWAS of AD and inverse-variance-weighted meta-analysis, followed by gene-level TWAS fine-mapping (MA-FOCUS), prioritizing nine genes (false discovery rate [FDR] <0.05, posterior inclusion probability [PIP] >0.8), including established AD loci (BIN1, PTK2B, DMPK) with broadly consistent effects across populations. At BIN1, fine-mapped cis-eQTL variants used in the TWAS prediction model highlighted rs11682128, which is only modestly correlated with the genome-wide association study (GWAS) index SNP rs6733839 (r

Indexed as

Alzheimer DiseaseGenetic Predisposition to DiseaseGenome-Wide Association StudyTranscriptomeBlack or African AmericanFemaleHispanic or LatinoHumansMalePolymorphism, Single NucleotideQuantitative Trait LociWhiteAlzheimer's diseaseeQTLmulti-ancestrytranscriptome-wide association study

Identifiers

PMID42066773
PMCPMC13247992

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