Evidence map›Paper›PMID 41174181›Full record

ArticleNature genetics2025

An African ancestry-specific nonsense variant in CD36 is associated with a higher risk of dilated cardiomyopathy.

Jennifer E Huffman, Liam Gaziano, Zeina R Al Sayed, Renae L Judy, Laura M Raffield, Kiran J Biddinger, Brian Charest, Anant Chopra, David Gagnon, Xiuqing Guo and 33 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 2 pooled it
–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

7 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Geographical and Ethnic Heterogeneity in Genetic Dilated Cardiomyopathies.International journal of molecular sciences · 2026
    Pooled it
  3. Article
  4. Review
  5. A CommonmedRxiv : the preprint server for health sciences · 2026
    Article
  6. Genetic factors contributing to atherosclerosis.Current opinion in cardiology · 2026
    Review
  7. 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

43 authors.

Jennifer E Huffman *VA Boston Healthcare System, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9672-2491
Liam Gaziano *VA Boston Healthcare System, Boston, MA, USA.
Zeina R Al Sayed *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Renae L JudyPerelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Laura M RaffieldUniversity of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kiran J BiddingerBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Brian CharestVA Boston Healthcare System, Boston, MA, USA.
Anant ChopraBayer US, LLC, Cambridge, MA, USA.
David GagnonVA Boston Healthcare System, Boston, MA, USA.
Xiuqing GuoThe Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID http://orcid.org/0000-0002-5264-5068
Vera KoledovaBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Michael G LevinPerelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9937-9932
Yuan-I MinUniversity of Mississippi Medical Center, Jackson, MS, USA.ORCID http://orcid.org/0000-0003-2470-0004
James P PirruccelloUniversity of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-6088-4037
Nosheen RezaPerelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Richard RuanBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Shefali Setia VermaUniversity of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-5216-4670
Bharath Ambale VenkateshJohns Hopkins University, Baltimore, MD, USA.
Anurag VermaUniversity of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-5063-9107
Jie YaoThe Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
John Jeffrey CarrVanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-4398-8237
Juan P CasasNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Kelly ChoVA Boston Healthcare System, Boston, MA, USA.
Joao A C LimaJohns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-8756-6995
Wendy S PostJohns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-8655-5204
Daniel J RaderPerelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9245-9876
Marylyn D RitchiePerelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Amil ShahUniversity of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0003-1056-4451
Kent D TaylorThe Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
James G TerryVanderbilt University Medical Center, Nashville, TN, USA.
Stephen S RichUniversity of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0003-3872-7793
Christopher J O'DonnellNovartis Institutes for Biomedical Research, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2667-8624
Lawrence S PhillipsEmory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-6542-8046
Kathryn L LunettaBoston University School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9268-810X
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID http://orcid.org/0000-0001-7191-1723
Peter W F WilsonEmory University School of Medicine, Atlanta, GA, USA.
J Michael GazianoVA Boston Healthcare System, Boston, MA, USA.
Scott M DamrauerPerelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8009-1632
VA Million Veteran Program
Yan V SunAtlanta VA Medical Center, Decatur, GA, USA.ORCID http://orcid.org/0000-0002-2838-1824
Patrick T EllinorBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2067-0533
Jacob JosephVA Boston Healthcare System, Boston, MA, USA. jacob.joseph@va.gov.ORCID http://orcid.org/0000-0002-7279-4896
Krishna G AragamVA Boston Healthcare System, Boston, MA, USA. karagam@broadinstitute.org.ORCID http://orcid.org/0000-0003-3223-9131

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILES Frome WILKINSON · 2003 to 2026
$40.4M
Wake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
Task Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2M
Studies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
Rare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00005 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WATSON, KAROL E · 2020 to 2025
$5.1M
BLRD VA I01 BX004821CSRD VA I01 CX001737CSRD VA I01 CX001922NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NHGRI NIH HHS U54 HG003067NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS HHSN268201100037CNHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS HHSN268201800010INHLBI NIH HHS HHSN268201800011CNHLBI NIH HHS HHSN268201800011INHLBI NIH HHS HHSN268201800012CNHLBI NIH HHS HHSN268201800012INHLBI NIH HHS HHSN268201800014CNHLBI NIH HHS HHSN268201800014INHLBI NIH HHS HHSN268201800015INHLBI NIH HHS K08 HL153937NHLBI NIH HHS K24 HL152008NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL143224NHLBI NIH HHS R01 HL160793NHLBI NIH HHS U01 HL120393NIDDK NIH HHS P30 DK063491NIMHD NIH HHS HHSN268201800013I
6 · The paper itself

Abstract

The high burden of dilated cardiomyopathy (DCM) in individuals of African descent remains incompletely explained. Here, to explore a genetic basis, we conducted a genome-wide association study in 1,802 DCM cases and 93,804 controls of African genetic ancestry (AFR). A nonsense variant ( rs3211938 :G) in CD36 was associated with increased risk of DCM. This variant, believed to be under positive selection due to a protective role in malaria resistance, is present in 17% of AFR individuals but <0.1% of European genetic ancestry (EUR) individuals. Homozygotes for the risk allele, who comprise ~1% of the AFR population, had approximately threefold higher odds of DCM. Among those without clinical cardiomyopathy, homozygotes exhibited an 8% absolute reduction in left ventricular ejection fraction. In AFR, the DCM population attributable fraction for the CD36 variant was 8.1%. This single variant accounted for approximately 20% of the excess DCM risk in individuals of AFR compared to those of EUR. Experiments in human induced pluripotent stem cell-derived cardiomyocytes demonstrated that CD36 loss of function impairs fatty acid uptake and disrupts cardiac metabolism and contractility. These findings implicate CD36 loss of function and suboptimal myocardial energetics as a prevalent cause of DCM in individuals of African descent.

Indexed as

Black PeopleCardiomyopathy, DilatedCD36 AntigensCodon, NonsenseGenetic Predisposition to DiseaseAdultCase-Control StudiesFemaleGenome-Wide Association StudyHumansMaleMiddle AgedMyocytes, CardiacPolymorphism, Single NucleotideRisk FactorsWhite PeopleCD36 AntigensCD36 protein, humanCodon, Nonsense

Identifiers

PMID41174181
PMCPMC12597818

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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.