Evidence map›Paper›PMID 40881139›Full record

ArticleNeurology. Genetics2024

Examining the Performance of Polygenic Risk Scores for Alzheimer Disease Within and Across Populations Using

Michael D Osterman, Yeunjoo E Song, Audrey Lynn, Kristy Miskimen, Nicholas R Wheeler, Jacquelaine Bartlett, Lindsay A Farrer, Gerard D Schellenberg, Eden R Martin, Margaret A Pericak-Vance and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology. Genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
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

13 authors.

Michael D OstermanFrom the Department of Population and Quantitative Health Sciences (M.D.O., Y.E.S., A.L., K.M., N.R.W., J.B., W.S.B., J.L.H.); Cleveland Institute for Computational Biology (M.D.O., Y.E.S., A.L., W.S.B., J.L.H.), Case Western Reserve University, OH; Department of Medicine (Biomedical Genetics) (L.A.F.), Boston University, Boston, MA; Penn Neurodegeneration Genomics Center (G.D.S.), Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia; The John P. Hussman Institute for Human Genomics (E.R.M., M.A.P.-V.), The University of Miami Miller School of Medicine; and Dr. John T. Macdonald Foundation Department of Human Genetics (E.R.M., M.A.P.-V.), University of Miami, Miami, FL.ORCID https://orcid.org/0000-0003-4302-6596
Yeunjoo E SongFrom the Department of Population and Quantitative Health Sciences (M.D.O., Y.E.S., A.L., K.M., N.R.W., J.B., W.S.B., J.L.H.); Cleveland Institute for Computational Biology (M.D.O., Y.E.S., A.L., W.S.B., J.L.H.), Case Western Reserve University, OH; Department of Medicine (Biomedical Genetics) (L.A.F.), Boston University, Boston, MA; Penn Neurodegeneration Genomics Center (G.D.S.), Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia; The John P. Hussman Institute for Human Genomics (E.R.M., M.A.P.-V.), The University of Miami Miller School of Medicine; and Dr. John T. Macdonald Foundation Department of Human Genetics (E.R.M., M.A.P.-V.), University of Miami, Miami, FL.
Audrey LynnFrom the Department of Population and Quantitative Health Sciences (M.D.O., Y.E.S., A.L., K.M., N.R.W., J.B., W.S.B., J.L.H.); Cleveland Institute for Computational Biology (M.D.O., Y.E.S., A.L., W.S.B., J.L.H.), Case Western Reserve University, OH; Department of Medicine (Biomedical Genetics) (L.A.F.), Boston University, Boston, MA; Penn Neurodegeneration Genomics Center (G.D.S.), Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia; The John P. Hussman Institute for Human Genomics (E.R.M., M.A.P.-V.), The University of Miami Miller School of Medicine; and Dr. John T. Macdonald Foundation Department of Human Genetics (E.R.M., M.A.P.-V.), University of Miami, Miami, FL.
Kristy MiskimenFrom the Department of Population and Quantitative Health Sciences (M.D.O., Y.E.S., A.L., K.M., N.R.W., J.B., W.S.B., J.L.H.); Cleveland Institute for Computational Biology (M.D.O., Y.E.S., A.L., W.S.B., J.L.H.), Case Western Reserve University, OH; Department of Medicine (Biomedical Genetics) (L.A.F.), Boston University, Boston, MA; Penn Neurodegeneration Genomics Center (G.D.S.), Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia; The John P. Hussman Institute for Human Genomics (E.R.M., M.A.P.-V.), The University of Miami Miller School of Medicine; and Dr. John T. Macdonald Foundation Department of Human Genetics (E.R.M., M.A.P.-V.), University of Miami, Miami, FL.ORCID https://orcid.org/0000-0003-0376-9053
Nicholas R WheelerFrom the Department of Population and Quantitative Health Sciences (M.D.O., Y.E.S., A.L., K.M., N.R.W., J.B., W.S.B., J.L.H.); Cleveland Institute for Computational Biology (M.D.O., Y.E.S., A.L., W.S.B., J.L.H.), Case Western Reserve University, OH; Department of Medicine (Biomedical Genetics) (L.A.F.), Boston University, Boston, MA; Penn Neurodegeneration Genomics Center (G.D.S.), Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia; The John P. Hussman Institute for Human Genomics (E.R.M., M.A.P.-V.), The University of Miami Miller School of Medicine; and Dr. John T. Macdonald Foundation Department of Human Genetics (E.R.M., M.A.P.-V.), University of Miami, Miami, FL.
Jacquelaine BartlettFrom the Department of Population and Quantitative Health Sciences (M.D.O., Y.E.S., A.L., K.M., N.R.W., J.B., W.S.B., J.L.H.); Cleveland Institute for Computational Biology (M.D.O., Y.E.S., A.L., W.S.B., J.L.H.), Case Western Reserve University, OH; Department of Medicine (Biomedical Genetics) (L.A.F.), Boston University, Boston, MA; Penn Neurodegeneration Genomics Center (G.D.S.), Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia; The John P. Hussman Institute for Human Genomics (E.R.M., M.A.P.-V.), The University of Miami Miller School of Medicine; and Dr. John T. Macdonald Foundation Department of Human Genetics (E.R.M., M.A.P.-V.), University of Miami, Miami, FL.
Lindsay A FarrerFrom the Department of Population and Quantitative Health Sciences (M.D.O., Y.E.S., A.L., K.M., N.R.W., J.B., W.S.B., J.L.H.); Cleveland Institute for Computational Biology (M.D.O., Y.E.S., A.L., W.S.B., J.L.H.), Case Western Reserve University, OH; Department of Medicine (Biomedical Genetics) (L.A.F.), Boston University, Boston, MA; Penn Neurodegeneration Genomics Center (G.D.S.), Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia; The John P. Hussman Institute for Human Genomics (E.R.M., M.A.P.-V.), The University of Miami Miller School of Medicine; and Dr. John T. Macdonald Foundation Department of Human Genetics (E.R.M., M.A.P.-V.), University of Miami, Miami, FL.ORCID https://orcid.org/0000-0001-5533-4225
Gerard D SchellenbergFrom the Department of Population and Quantitative Health Sciences (M.D.O., Y.E.S., A.L., K.M., N.R.W., J.B., W.S.B., J.L.H.); Cleveland Institute for Computational Biology (M.D.O., Y.E.S., A.L., W.S.B., J.L.H.), Case Western Reserve University, OH; Department of Medicine (Biomedical Genetics) (L.A.F.), Boston University, Boston, MA; Penn Neurodegeneration Genomics Center (G.D.S.), Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia; The John P. Hussman Institute for Human Genomics (E.R.M., M.A.P.-V.), The University of Miami Miller School of Medicine; and Dr. John T. Macdonald Foundation Department of Human Genetics (E.R.M., M.A.P.-V.), University of Miami, Miami, FL.ORCID https://orcid.org/0000-0003-1115-2475
Eden R MartinFrom the Department of Population and Quantitative Health Sciences (M.D.O., Y.E.S., A.L., K.M., N.R.W., J.B., W.S.B., J.L.H.); Cleveland Institute for Computational Biology (M.D.O., Y.E.S., A.L., W.S.B., J.L.H.), Case Western Reserve University, OH; Department of Medicine (Biomedical Genetics) (L.A.F.), Boston University, Boston, MA; Penn Neurodegeneration Genomics Center (G.D.S.), Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia; The John P. Hussman Institute for Human Genomics (E.R.M., M.A.P.-V.), The University of Miami Miller School of Medicine; and Dr. John T. Macdonald Foundation Department of Human Genetics (E.R.M., M.A.P.-V.), University of Miami, Miami, FL.
Margaret A Pericak-VanceFrom the Department of Population and Quantitative Health Sciences (M.D.O., Y.E.S., A.L., K.M., N.R.W., J.B., W.S.B., J.L.H.); Cleveland Institute for Computational Biology (M.D.O., Y.E.S., A.L., W.S.B., J.L.H.), Case Western Reserve University, OH; Department of Medicine (Biomedical Genetics) (L.A.F.), Boston University, Boston, MA; Penn Neurodegeneration Genomics Center (G.D.S.), Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia; The John P. Hussman Institute for Human Genomics (E.R.M., M.A.P.-V.), The University of Miami Miller School of Medicine; and Dr. John T. Macdonald Foundation Department of Human Genetics (E.R.M., M.A.P.-V.), University of Miami, Miami, FL.
William S BushFrom the Department of Population and Quantitative Health Sciences (M.D.O., Y.E.S., A.L., K.M., N.R.W., J.B., W.S.B., J.L.H.); Cleveland Institute for Computational Biology (M.D.O., Y.E.S., A.L., W.S.B., J.L.H.), Case Western Reserve University, OH; Department of Medicine (Biomedical Genetics) (L.A.F.), Boston University, Boston, MA; Penn Neurodegeneration Genomics Center (G.D.S.), Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia; The John P. Hussman Institute for Human Genomics (E.R.M., M.A.P.-V.), The University of Miami Miller School of Medicine; and Dr. John T. Macdonald Foundation Department of Human Genetics (E.R.M., M.A.P.-V.), University of Miami, Miami, FL.ORCID https://orcid.org/0000-0002-9729-6519
Jonathan L HainesFrom the Department of Population and Quantitative Health Sciences (M.D.O., Y.E.S., A.L., K.M., N.R.W., J.B., W.S.B., J.L.H.); Cleveland Institute for Computational Biology (M.D.O., Y.E.S., A.L., W.S.B., J.L.H.), Case Western Reserve University, OH; Department of Medicine (Biomedical Genetics) (L.A.F.), Boston University, Boston, MA; Penn Neurodegeneration Genomics Center (G.D.S.), Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia; The John P. Hussman Institute for Human Genomics (E.R.M., M.A.P.-V.), The University of Miami Miller School of Medicine; and Dr. John T. Macdonald Foundation Department of Human Genetics (E.R.M., M.A.P.-V.), University of Miami, Miami, FL.
as the Alzheimer's Disease Sequencing Project (ADSP)

Funding

The Alzheimer Disease Sequence Analysis CollaborativeU01AG058654 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI BUSH, WILLIAM S, FARRER, LINDSAY A. · 2018 to 2022
$14.6M
Protective Genetic Varients for Alzheimer Disease in the AmishR01AG058066 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI Jonathan L Haines, Margaret A. Pericak-Vance · 2022 to 2026
$8.0M
NIA NIH HHS R01 AG058066NIA NIH HHS U01 AG058654
6 · The paper itself

Abstract

Background and Objectives: Alzheimer disease (AD) has a complex etiology with a strong genetic component. Despite mounting evidence that genetic risk effect sizes vary by population, most research on the genetics of AD has examined only data sets of individuals with European ancestry. In this study, we investigate the variable performance and transferability of polygenic risk scores (PRSs) by deriving a PRS from analyses of AD for various race and ethnic categories and applying this across groups using a Methods: After quality control and application of inclusion criteria, we analyzed 11,254 individuals from the Alzheimer's Disease Sequencing Project Release 3 with 3 predominant self-identified race/ethnicity groups: Hispanic individuals (n = 2,207), non-Hispanic Black individuals (n = 2,437), and non-Hispanic White individuals (n = 6,610). For each group, a 5-fold cross-validation approach was used to perform a genome-wide association study (training) and construct PRS estimates (test). This approach allowed for consideration of within-group and across-group PRS performance. Area under the curve (AUC) was calculated for each race/ethnicity-specific PRS within each cross-validation fold. Various PRS criteria were considered, including rare single-nucleotide polymorphisms and the Results: Across all participant groups, the PRS trained in the same race/ethnicity category as the test group nearly exclusively outperformed the other PRSs with considerable benefit in the Hispanic group. The range of AUCs across iterations was also greater when applying PRSs from other groups. These findings were consistent after inclusion of Discussion: In this study, we demonstrated the variable performance of AD PRSs within race/ethnicity groups and the weakness in transferability across groups, accounting for different criteria in PRS calculation. This work provided a framework for improving PRS application for AD and highlighted the importance of recruiting diverse populations in genetic studies.

Identifiers

PMID40881139
PMCPMC11727989

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.