Evidence map›Paper›PMID 37745480›Full record

ArticlebioRxiv : the preprint server for biology2023

Whole Genome Sequencing Based Analysis of Inflammation Biomarkers in the Trans-Omics for Precision Medicine (TOPMed) Consortium.

Min-Zhi Jiang, Sheila M Gaynor, Xihao Li, Eric Van Buren, Adrienne Stilp, Erin Buth, Fei Fei Wang, Regina Manansala, Stephanie M Gogarten, Zilin Li and 37 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

47 authors at 20 institutions in 5 countries.

Min-Zhi JiangDepartment of Genetics, University of North Carolina at Chapel Hill, 120 Mason Farm Road, Chapel Hill, NC, 27599, USA.
Sheila M GaynorDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, MA, 02115, USA.
Xihao LiDepartment of Genetics, University of North Carolina at Chapel Hill, 120 Mason Farm Road, Chapel Hill, NC, 27599, USA.
Eric Van BurenDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, MA, 02115, USA.
Adrienne StilpDepartment of Biostatistics, University of Washington, Seattle, WA, 98105, USA.
Erin ButhDepartment of Biostatistics, University of Washington, Seattle, WA, 98105, USA.
Fei Fei WangDepartment of Biostatistics, University of Washington, Seattle, WA, 98105, USA.
Regina ManansalaCentre for Health Economics Research & Modelling Infectious Diseases (CHERMID), Vaccine & Infectious Disease Institute (VAXINFECTIO) WHO Collaborating Centre, University of Antwerp, Antwerp, BE.
Stephanie M GogartenDepartment of Biostatistics, University of Washington, Seattle, WA, 98105, USA.
Zilin LiSchool of Mathematics and Statistics, Northeast Normal University, Changchun, Jilin, 130024, China.
Linda M PolfusDepartment of Preventive Medicine, Center for Genetic Epidemiology, University of Southern California, Los Angeles, CA, 90033, USA.
Shabnam SalimiDepartment of Epidemiology and Public Health, Division of Gerontology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, 4333 Brooklyn Ave NE, Box 359458, Seattle, WA, 98195, USA.
Nathan PankratzDepartment of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
Lisa R YanekDepartment of Medicine, General Internal Medicine, Johns Hopkins University School of Medicine, 1830 E Monument St Rm 8024, Baltimore, MD, 21287, USA.
Peter DurdaDepartment of Pathology & Laboratory Medicine, University of Vermont Larner College of Medicine, 360 South Park Drive, Colchester, VT, 05446, USA.
Russell P TracyDepartment of Pathology & Laboratory Medicine, University of Vermont Larner College of Medicine, 360 South Park Drive, Colchester, VT, 05446, USA.
Stephen S RichCenter for Public Health Genomics, University of Virginia School of Medicine, 200 Jeanette Lancaster Way, Charlottesville, VA, 22903, USA.
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, 1124 W. Carson Street, Torrance, CA, 90502, USA.
Braxton D MitchellDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, 670 W. Baltimore St., Baltimore, MD, 21201, USA.
Joshua P LewisDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, 670 W. Baltimore St., Baltimore, MD, 21201, USA.
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, University of Washington, 4333 Brooklyn Ave NE, Box 359458, Seattle, WA, 98195, USA.
Katherine A PratteDepartment of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, Denver, CO, 80206, USA.
Edwin K SilvermanDepartment of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA, 02115, USA.
Robert C KaplanDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Christy AveryDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Kari NorthDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Rasika A MathiasDepartment of Medicine, Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Cir JHAAC Room 3B53, Baltimore, MD, 21287, USA.
Nauder FaradayDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 N Wolfe St, Baltimore, MD, 21287, USA.
Honghuang LinDepartment of Medicine, University of Massachusetts Chan Medical School, 55 Lake Ave North, Worcester, MA, 01655, USA.
Biqi WangDepartment of Medicine, University of Massachusetts Chan Medical School, 55 Lake Ave North, Worcester, MA, 01655, USA.
April P CarsonDepartment of Medicine, University of Mississippi Medical Center, 350 W. Woodrow Wilson Avenue, Suite 701, Jackson, MS, 39213, USA.
Arnita F NorwoodDepartment of Medicine, University of Mississippi Medical Center, 350 W. Woodrow Wilson Avenue, Suite 701, Jackson, MS, 39213, USA.
Richard A GibbsDepartment of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Jessica LundinDivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Ulrike PetersDivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Josée DupuisDepartment of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec, H3A 1G1, Canada.
Lifang HouDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Myriam FornageBrown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Emelia J BenjaminDepartment of Medicine, Cardiovascular Medicine, Boston Medical Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, 02118, USA.
Alexander P ReinerDepartment of Epidemiology, University of Washington, Seattle, WA, 98105, USA.
Russell P BowlerDepartment of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, Denver, CO, 80206, USA.
Xihong LinDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, MA, 02115, USA.
Paul L AuerDivision of Biostatistics, Institute for Health and Equity, and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
Laura M RaffieldDepartment of Genetics, University of North Carolina at Chapel Hill, 120 Mason Farm Road, Chapel Hill, NC, 27599, USA.
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Inflammation Working Group
University of Washington · USUniversity of North Carolina at Chapel Hill · USCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZAHarvard University · USJohns Hopkins University · USUniversity of Maryland, Baltimore · USBoston University · USNational Jewish Health · USUniversity of Massachusetts Chan Medical School · USUniversity of Mississippi Medical Center · USUniversity of Vermont · USAlbert Einstein College of Medicine · USBaylor College of Medicine · USBrigham and Women's Hospital · USBrown Foundation · USInfectious Diseases Institute · UGMedical College of Wisconsin · USNortheast Normal University · CNNorthwestern University · USOffice of Public Health Genomics · US

Funding

NHLBI Data Stage Coordinating CenterOT3HL147154 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Ashok Kumar Krishnamurthy · 2018 to 2026
$98.9M
The Integration of Trans-omics for Precision Medicine (TOPMED) and Other Heart, Lung, Blood and Sleep (HLBS) Data Sets with the Data CommonsOT3HL142481 · NHLBI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI GROSSMAN, ROBERT L., PATEN, BENEDICT · 2017 to 2020
$24.9M
The Integration of Trans-omics for Precision Medicine (TOPMED) and Other Heart, Lung, Blood and Sleep (HLBS) Data Sets with the Data CommonsOT3HL142478 · NHLBI · SEVEN BRIDGES GENOMICS, INC. · PI DAVIS-DUSENBERY, BRANDI NICOLE · 2017 to 2022
$12.6M
North Carolina Translational and Clinical Science Institute (NC TraCS) KL2KL2TR002490 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WEINBERGER, MORRIS · 2018 to 2022
$11.0M
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
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
The Integration of Trans-omics for Precision Medicine (TOPMED) and Other Heart, Lung, Blood and Sleep (HLBS) Data Sets with the Data CommonsOT3HL142480 · NHLBI · HARVARD MEDICAL SCHOOL · PI AVILLACH, PAUL · 2017 to 2022
$8.8M
PAGE III: Population Architecture using Genomics and EpidemiologyR01HG010297 · NHGRI · RUTGERS, THE STATE UNIV OF N.J. · PI GIGNOUX, CHRISTOPHER R, MATISE, TARA C. · 2019 to 2022
$6.5M
The Integration of Trans-omics for Precision Medicine (TOPMED) and Other Heart, Lung, Blood and Sleep (HLBS) Data Sets with the Data CommonsOT3HL142479 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KRISHNAMURTHY, ASHOK KUMAR · 2017 to 2020
$6.1M
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
Powering whole genome sequence-based genetic discovery for common human diseases- Extended 2021-2022.U01HG009088 · NHGRI · HARVARD SCHOOL OF PUBLIC HEALTH · PI LIN, XIHONG, NEALE, BENJAMIN MICHAEL · 2016 to 2021
$5.1M
Predictive Modeling of the Functional and Phenotypic Impacts of Genetic VariantsU01HG012064 · NHGRI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Manuel Garber, XIHONG LIN · 2021 to 2026
$4.0M
NCATS NIH HHS KL2 TR002490NHGRI NIH HHS R01 HG010297NHGRI NIH HHS U01 HG009088NHGRI NIH HHS U01 HG012064NHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS OT3 HL142478NHLBI NIH HHS OT3 HL142479NHLBI NIH HHS OT3 HL142480NHLBI NIH HHS OT3 HL142481NHLBI NIH HHS OT3 HL147154NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL163560NHLBI NIH HHS U01 HL120393
6 · The paper itself

Abstract

Inflammation biomarkers can provide valuable insight into the role of inflammatory processes in many diseases and conditions. Sequencing based analyses of such biomarkers can also serve as an exemplar of the genetic architecture of quantitative traits. To evaluate the biological insight, which can be provided by a multi-ancestry, whole-genome based association study, we performed a comprehensive analysis of 21 inflammation biomarkers from up to 38,465 individuals with whole-genome sequencing from the Trans-Omics for Precision Medicine (TOPMed) program. We identified 22 distinct single-variant associations across 6 traits - E-selectin, intercellular adhesion molecule 1, interleukin-6, lipoprotein-associated phospholipase A2 activity and mass, and P-selectin - that remained significant after conditioning on previously identified associations for these inflammatory biomarkers. We further expanded upon known biomarker associations by pairing the single-variant analysis with a rare variant set-based analysis that further identified 19 significant rare variant set-based associations with 5 traits. These signals were distinct from both significant single variant association signals within TOPMed and genetic signals observed in prior studies, demonstrating the complementary value of performing both single and rare variant analyses when analyzing quantitative traits. We also confirm several previously reported signals from semi-quantitative proteomics platforms. Many of these signals demonstrate the extensive allelic heterogeneity and ancestry-differentiated variant-trait associations common for inflammation biomarkers, a characteristic we hypothesize will be increasingly observed with well-powered, large-scale analyses of complex traits.

Identifiers

PMID37745480
PMCPMC10515765
OpenAlexW4387002000

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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.