Evidence map›Paper›PMID 37766997›Full record

ArticleiScience2023

Bayesian multivariate genetic analysis improves translational insights.

Sarah M Urbut, Satoshi Koyama, Whitney Hornsby, Rohan Bhukar, Sumeet Kheterpal, Buu Truong, Margaret S Selvaraj, Benjamin Neale, Christopher J O'Donnell, Gina M Peloso and 1 more

Abstract read
In one paragraph

Article in iScience, 2023. 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

11 authors.

Sarah M UrbutCardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Satoshi KoyamaCardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Whitney HornsbyCardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Rohan BhukarCardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Sumeet KheterpalCardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Buu TruongCardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Margaret S SelvarajCardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Benjamin NealeProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA.
Christopher J O'DonnellDepartment of Medicine Harvard Medical School, Boston, MA 02115, USA.
Gina M PelosoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02218, USA.
Pradeep NatarajanCardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.

Funding

Polygenic Risk Scores for Diverse Populations - Bridging Research and Clinical CareR01HL151152 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Christy Leigh Avery, Jennifer Below · 2020 to 2026
$12.3M
Using genetic variation to study biology of blood lipids & coronary heart diseaseR01HL127564 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pradeep Natarajan, Gina Marie Peloso · 2015 to 2026
$7.3M
Clonal hematopoiesis in the Womens Health Initiative Memory StudyR01HL148565 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ALEXANDER P REINER, Eric A. Whitsel · 2019 to 2026
$5.9M
Clonal hematopoiesis in humans: determinants of development and progressionR01HL148050 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI BALLANTYNE, CHRISTIE MITCHELL, NATARAJAN, PRADEEP · 2019 to 2022
$5.9M
Whole genome sequences in individuals to comprehensively characterize the genetic mechanisms of dyslipidemiasR01HL142711 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Satoshi Koyama, Gina Marie Peloso · 2019 to 2026
$4.7M
CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL IN CHRONIC KIDNEY DISEASE PATIENTSR01DK125782 · NIDDK · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KELLY, TANIKA NICOLE · 2021 to 2025
$3.3M
Partners Healthcare Training Program in Precision and Genomic MedicineT32HG010464 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI HEIDI L REHM, JORDAN W SMOLLER · 2019 to 2026
$3.1M
Clonal hematopoiesis of indeterminate potential and HIV in the REPRIEVE trialR01HL151283 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI NATARAJAN, PRADEEP · 2020 to 2023
$2.5M
Whole genome sequence interpretation for lipids to discover new genes and mechanisms for coronary artery diseaseK99HL169733 · NHLBI · BROAD INSTITUTE, INC. · PI KOYAMA, SATOSHI · 2023 to 2024
$330k
NHGRI NIH HHS T32 HG010464NHLBI NIH HHS K99 HL169733NHLBI NIH HHS R01 HL127564NHLBI NIH HHS R01 HL142711NHLBI NIH HHS R01 HL148050NHLBI NIH HHS R01 HL148565NHLBI NIH HHS R01 HL151152NHLBI NIH HHS R01 HL151283NIDDK NIH HHS R01 DK125782
6 · The paper itself

Abstract

While lipid traits are known essential mediators of cardiovascular disease, few approaches have taken advantage of their shared genetic effects. We apply a Bayesian multivariate size estimator, mash, to GWAS of four lipid traits in the Million Veterans Program (MVP) and provide posterior mean and local false sign rates for all effects. These estimates borrow information across traits to improve effect size accuracy. We show that controlling local false sign rates accurately and powerfully identifies replicable genetic associations and that multivariate control furthers the ability to explain complex diseases. Our application yields high concordance between independent datasets, more accurately prioritizes causal genes, and significantly improves polygenic prediction beyond state-of-the-art methods by up to 59% for lipid traits. The use of Bayesian multivariate genetic shrinkage has yet to be applied to human quantitative trait GWAS results, and we present a staged approach to prediction on a polygenic scale.

Indexed as

Association analysisBiocomputational methodComputational bioinformaticsGenomic analysisHuman genetics

Identifiers

PMID37766997
PMCPMC10520309

What OpenQuestion 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 OpenQuestion graph.