Evidence map›Paper›PMID 34282949›Full record

ArticleCirculation. Genomic and precision medicine2021

Associations of Genetically Predicted Lp(a) (Lipoprotein [a]) Levels With Cardiovascular Traits in Individuals of European and African Ancestry.

Benjamin A Satterfield, Ozan Dikilitas, Maya S Safarova, Shoa L Clarke, Catherine Tcheandjieu, Xiang Zhu, Lisa Bastarache, Eric B Larson, Anne E Justice, Ning Shang and 12 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation. Genomic and precision medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.6field-weighted citation impact, top 4% of its field
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

25 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Genetic Prediction of Circulating Lipoprotein(a) Levels in Diverse Populations.medRxiv : the preprint server for health sciences · 2026
    Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Observational
  8. Review
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  10. Review
  11. Article
  12. Article
  13. Lipoprotein(a) and panvascular disease.Lipids in health and disease · 2025
    Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2023
    Review
  19. Article
  20. 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

22 authors at 13 institutions in 1 country.

Benjamin A Satterfield *Department of Cardiovascular Medicine (B.A.S., O.D., M.S.S., I.J.K.), Mayo Clinic, Rochester, MN.
Ozan Dikilitas *Department of Cardiovascular Medicine (B.A.S., O.D., M.S.S., I.J.K.), Mayo Clinic, Rochester, MN.
Maya S SafarovaDepartment of Cardiovascular Medicine (B.A.S., O.D., M.S.S., I.J.K.), Mayo Clinic, Rochester, MN.
Shoa L ClarkeVA Palo Alto Health Care System, Palo Alto (S.L.C., C.T., X.Z., T.L.A.).
Catherine TcheandjieuVA Palo Alto Health Care System, Palo Alto (S.L.C., C.T., X.Z., T.L.A.).
Xiang ZhuVA Palo Alto Health Care System, Palo Alto (S.L.C., C.T., X.Z., T.L.A.).
Lisa BastaracheDepartment of Biomedical Informatics, Vanderbilt University, Nashville, TN (L.B., W.-Q.W.).
Eric B LarsonKaiser Permanente Washington Health Research Institutes, Seattle (E.B.L.).
Anne E JusticeDepartment of Population Health Sciences, Geisinger, Danville, PA (A.E.J.).
Ning ShangDepartment of Biomedical Informatics, Columbia University, New York, NY (N.S.).
Elisabeth A RosenthalDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle (E.A.R., G.P.J.).
Amy Sanghavi ShahDivision of Endocrinology (A.S.S.), Cincinnati Children's Hospital Medical Center & University of Cincinnati.
Bahram Namjou-KhalesCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center & Department of Pediatrics, University of Cincinnati College of Medicine, OH (B.-N.K.).
Elaine M UrbinaHeart Institute (E.M.U.), Cincinnati Children's Hospital Medical Center & University of Cincinnati.
Wei-Qi WeiDepartment of Biomedical Informatics, Vanderbilt University, Nashville, TN (L.B., W.-Q.W.).
QiPing FengDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (Q.F.).
Gail P JarvikDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle (E.A.R., G.P.J.).
Scott J HebbringCenter for Precision Medicine, Marshfield Clinic Research Institute, WI (S.J.H.).
Mariza de AndradeDepartment of Health Sciences Research (M.d.A.), Mayo Clinic, Rochester, MN.
Teri A ManolioDivision of Genomic Medicine, National Human Genome Research Institute, Bethesda, MD (T.A.M.).
Themistocles L AssimesVA Palo Alto Health Care System, Palo Alto (S.L.C., C.T., X.Z., T.L.A.).
Iftikhar J KulloDepartment of Cardiovascular Medicine (B.A.S., O.D., M.S.S., I.J.K.), Mayo Clinic, Rochester, MN.
Mayo Clinic · USCincinnati Children's Hospital Medical Center · USVA Palo Alto Health Care System · USUniversity of Washington Medical Center · USVanderbilt University · USColumbia University · USGeisinger Medical Center · USKaiser Permanente Washington Health Research Institute · USMarshfield Clinic · USMayo Clinic in Arizona · USNational Human Genome Research Institute · USPennsylvania State University · USVanderbilt University Medical Center · US

Funding

JH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2M
A Center for GEI Association StudiesU01HG004424 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY · 2007 to 2010
$21.4M
Genomic Basis of Susceptibility to COVID-19 Infection and its ComplicationsU01HG006379 · NHGRI · MAYO CLINIC ROCHESTER · PI Richard R. Sharp · 2011 to 2026
$16.5M
OMOP information model for eMERGE phenotypingU01HG008680 · NHGRI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Wendy K Chung, GEORGE M HRIPCSAK · 2015 to 2026
$13.3M
Vanderbilt Genome-Electronic Records ProjectU01HG004603 · NHGRI · VANDERBILT UNIVERSITY · PI RODEN, DAN M · 2007 to 2011
$7.3M
eMERGE Coordinating Center - Administrative SupplementU01HG006385 · NHGRI · VANDERBILT UNIVERSITY · PI HARRIS, PAUL A. · 2011 to 2014
$5.4M
Biorepository for Genomic Medicine in diverse CommunitiesU01HG006380 · NHGRI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BOTTINGER, ERWIN P. · 2011 to 2015
$4.5M
Geisinger eGenonic Medicine (GeM) ProgramU01HG006382 · NHGRI · GEISINGER CLINIC · PI CAREY, DAVID J., WILLIAMS, MARC S. · 2011 to 2014
$4.3M
Development and Use of Network Infrastructure for High-Throughput GWA StudiesU01HG004610 · NHGRI · KAISER FOUNDATION HEALTH PLAN OF WASHINGTON · PI LARSON, ERIC B · 2007 to 2010
$4.2M
A Personalized Genomic Medicine Pilot Program Using the NJgene eMERGE ExperienceU01HG006388 · NHGRI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHISHOLM, REX L, SMITH, MAUREEN E · 2011 to 2014
$4.1M
IRIS: Incorporating Research Into SightU01HG006389 · NHGRI · ESSENTIA INSTITUTE OF RURAL HEALTH · PI MCCARTY, CATHERINE ANNE · 2011 to 2014
$4.1M
Genetic Discovery and Application in a Clinical Setting Continuing a PartnershipU01HG006375 · NHGRI · KAISER FOUNDATION HEALTH PLAN OF WASHINGTON · PI JARVIK, GAIL PAIRITZ, LARSON, ERIC B · 2011 to 2014
$4.1M
BLRD VA I01 BX003362NHGRI NIH HHS U01 HG004424NHGRI NIH HHS U01 HG004438NHGRI NIH HHS U01 HG004599NHGRI NIH HHS U01 HG004603NHGRI NIH HHS U01 HG004608NHGRI NIH HHS U01 HG004609NHGRI NIH HHS U01 HG004610NHGRI NIH HHS U01 HG006375NHGRI NIH HHS U01 HG006378NHGRI NIH HHS U01 HG006379NHGRI NIH HHS U01 HG006380NHGRI NIH HHS U01 HG006382NHGRI NIH HHS U01 HG006385NHGRI NIH HHS U01 HG006388NHGRI NIH HHS U01 HG006389NHGRI NIH HHS U01 HG008680NHLBI NIH HHS K24 HL137010
6 · The paper itself

Abstract

backgroundLp(a) (lipoprotein [a]) levels are higher in individuals of African ancestry (AA) than in individuals of European ancestry (EA). We examined associations of genetically predicted Lp(a) levels with (1) atherosclerotic cardiovascular disease subtypes: coronary heart disease, cerebrovascular disease, peripheral artery disease, and abdominal aortic aneurysm and (2) nonatherosclerotic cardiovascular disease phenotypes, stratified by ancestry.

methodsWe performed (1) Mendelian randomization analyses for previously reported cardiovascular associations and (2) Mendelian randomization-phenome-wide association analyses for novel associations. Analyses were stratified by ancestry in electronic Medical Records and Genomics, United Kingdom Biobank, and Million Veteran Program cohorts separately and in a combined cohort of 804 507 EA and 103 580 AA participants.

resultsIn Mendelian randomization analyses using the combined cohort, a 1-SD genetic increase in Lp(a) level was associated with atherosclerotic cardiovascular disease subtypes in EA-odds ratio and 95% CI for coronary heart disease 1.28 (1.16-1.41); cerebrovascular disease 1.14 (1.07-1.21); peripheral artery disease 1.22 (1.11-1.34); abdominal aortic aneurysm 1.28 (1.17-1.40); in AA, the effect estimate was lower than in EA and nonsignificant for coronary heart disease 1.11 (0.99-1.24) and cerebrovascular disease 1.06 (0.99-1.14) but similar for peripheral artery disease 1.16 (1.01-1.33) and abdominal aortic aneurysm 1.34 (1.11-1.62). In EA, a 1-SD genetic increase in Lp(a) level was associated with aortic valve disorders 1.34 (1.10-1.62), mitral valve disorders 1.18 (1.09-1.27), congestive heart failure 1.12 (1.05-1.19), and chronic kidney disease 1.07 (1.01-1.14). In AA, no significant associations were noted for aortic valve disorders 1.08 (0.94-1.25), mitral valve disorders 1.02 (0.89-1.16), congestive heart failure 1.02 (0.95-1.10), or chronic kidney disease 1.05 (0.99-1.12). Mendelian randomization-phenome-wide association analyses identified novel associations in EA with arterial thromboembolic disease, nonaortic aneurysmal disease, atrial fibrillation, cardiac conduction disorders, and hypertension.

conclusionsMany cardiovascular associations of genetically increased Lp(a) that were significant in EA were not significant in AA. Lp(a) was associated with atherosclerotic cardiovascular disease in four major arterial beds in EA but only with peripheral artery disease and abdominal aortic aneurysm in AA. Additionally, novel cardiovascular associations were detected in EA.

Indexed as

Genetic Predisposition to DiseaseQuantitative Trait, HeritableAgedAged, 80 and overBlack PeopleCardiovascular DiseasesFemaleHumansLipoprotein(a)MaleMendelian Randomization AnalysisMiddle AgedUnited KingdomWhite PeopleLipoprotein(a)LPA protein, humanatherosclerosiscardiovascular diseaseheart failurelipoproteinMendelian randomization analysis

Identifiers

PMID34282949
PMCPMC8634549
OpenAlexW3185131304

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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.