Evidence map›Paper›PMID 31883642›Full record

ArticleAmerican journal of human genetics2020

Allelic Heterogeneity at the CRP Locus Identified by Whole-Genome Sequencing in Multi-ancestry Cohorts.

Laura M Raffield, Apoorva K Iyengar, Biqi Wang, Sheila M Gaynor, Cassandra N Spracklen, Xue Zhong, Madeline H Kowalski, Shabnam Salimi, Linda M Polfus, Emelia J Benjamin and 42 more

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Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Review
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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

52 authors.

Laura M RaffieldDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
Apoorva K IyengarDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
Biqi WangDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
Sheila M GaynorDepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
Cassandra N SpracklenDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
Xue ZhongDepartment of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, TN 37232, USA.
Madeline H KowalskiDepartment of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA.
Shabnam SalimiDepartment of Epidemiology and Public Health, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
Linda M PolfusDepartment of Preventive Medicine, Center for Genetic Epidemiology, University of Southern California, Los Angeles, CA 90089, USA.
Emelia J BenjaminDepartment of Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01702, USA.
Joshua C BisDepartment of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA 98101, USA.
Russell BowlerDepartment of Medicine, Division of Pulmonary, Critical Care & Sleep Medicine, National Jewish Health, Denver, CO 80206, USA.
Brian E CadeDepartment of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA.
Won Jung ChoiMacrogen USA, Rockville, MD 20850, USA.
Alejandro P ComellasDepartment of Medicine, Division of Pulmonary and Critical Care, University of Iowa, Iowa City, IA 52242, USA.
Adolfo CorreaDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Pedro CruzIllumina Laboratory Services, Illumina Inc., San Diego, CA 92122, USA.
Harsha DoddapaneniHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Peter DurdaDepartment of Pathology & Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05446, USA.
Stephanie M GogartenDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
Deepti JainDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
Ryan W KimMacrogen USA, Rockville, MD 20850, USA.
Brian G KralGeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Leslie A LangeDepartment of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA.
Martin G LarsonDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01702, USA.
Cecelia LaurieDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
Jiwon LeeDepartment of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115, USA.
Seonwook LeeMacrogen USA, Rockville, MD 20850, USA.
Joshua P LewisDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Ginger A MetcalfHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Braxton D MitchellDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD 21201, USA.
Zeineen MominHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Donna M MuznyHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Nathan PankratzDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Cheol Joo ParkMacrogen USA, Rockville, MD 20850, USA.
Stephen S RichDepartment of Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Kathleen RyanDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Daekwan SeoMacrogen USA, Rockville, MD 20850, USA.
Russell P TracyDepartment of Pathology & Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05446, USA; Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, VT 05446, USA.
Karine A Viaud-MartinezIllumina Laboratory Services, Illumina Inc., San Diego, CA 92122, USA.
Lisa R YanekGeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Lue Ping ZhaoDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; School of Public Health, University of Washington, Seattle, WA 98195, USA.
Xihong LinDepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Statistics, Harvard University, Cambridge, MA 02138, USA.
Bingshan LiDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA.
Yun LiDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Computer Science, University of North Carolina, Chapel Hill, NC 27599, USA.
Josée DupuisDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01702, USA.
Alexander P ReinerDepartment of Epidemiology, University of Washington, Seattle, WA 98195, USA.
Karen L MohlkeDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
Paul L AuerJoseph J. Zilber School of Public Health, University of Wisconsin Milwaukee, Milwaukee, WI 53205, USA. Electronic address: pauer@uwm.edu.
TOPMed Inflammation Working Group
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium

Funding

Pulmonary Toxicology Facility CoreP30ES005605 · NIEHS · UNIVERSITY OF IOWA · PI Andrea Adamcakova-Dodd · 1990 to 2026
$40.5M
Targeted Genetic Analysis of T2D and Quantitative TraitsR01DK072193 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2005 to 2026
$11.3M
Statistical Methods for Analysis of Massive Genetic and Genomic Data in Cancer ResearchR35CA197449 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI XIHONG LIN · 2015 to 2026
$10.9M
Analysis, Validation and Resource Creation for Genome Sequencing of Complex DiseasesU01HG009086 · NHGRI · VANDERBILT UNIVERSITY · PI COX, NANCY J, LI, BINGSHAN · 2016 to 2020
$4.3M
Framingham: Inflammation, Genes &Cardiovascular DiseaseR01HL076784 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BENJAMIN, EMELIA J. · 2004 to 2008
$3.9M
The Genetic Epidemiology of Heart, Lung, and Blood TraitsTraining Grant (GenHLB)T32HL129982 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Christy Leigh Avery, KAREN L. MOHLKE · 2016 to 2026
$3.8M
AFGen Consortium: Atrial Fibrillation Genomics to Functional AnalysesR01HL128914 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2015 to 2018
$3.1M
Thrombosis genetics in African AmericansR01HL132947 · NHLBI · UNIVERSITY OF WASHINGTON · PI LANGE, LESLIE A, REINER, ALEXANDER P · 2017 to 2020
$3.1M
Genetic Studies of Blood Cell Traits in Multi-Ethnic CohortsR01HL129132 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LI, YUN, REINER, ALEXANDER P · 2016 to 2019
$2.7M
T-cell subsets as CVD risk factors in CHS and MESAR01HL120854 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, TRACY, RUSSELL P · 2014 to 2017
$2.6M
Functional genetic variants for type 2 diabetesU01DK105561 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MOHLKE, KAREN L. · 2015 to 2019
$2.3M
The Impact of Carboxylesterase 1 ( CES1 ) in Personalized Antiplalet TherapyR01HL137922 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI LEWIS, JOSHUA PATRICK · 2017 to 2021
$1.9M
NCI NIH HHS R35 CA197449NHGRI NIH HHS U01 HG009086NHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS HHSN268201800010INHLBI NIH HHS HHSN268201800011CNHLBI NIH HHS HHSN268201800011INHLBI NIH HHS HHSN268201800012CNHLBI NIH HHS HHSN268201800012INHLBI NIH HHS HHSN268201800015INHLBI NIH HHS K01 HL135405NHLBI NIH HHS N01 HC025195NHLBI NIH HHS R01 HL076784NHLBI NIH HHS R01 HL120854NHLBI NIH HHS R01 HL128914NHLBI NIH HHS R01 HL129132NHLBI NIH HHS R01 HL132947NHLBI NIH HHS R01 HL137922NHLBI NIH HHS T32 HL129982NIA NIH HHS K01 AG059898NIA NIH HHS R01 AG028321NIDDK NIH HHS R01 DK072193NIDDK NIH HHS U01 DK105561NIEHS NIH HHS P30 ES005605NIMHD NIH HHS HHSN268201800013I
6 · The paper itself

Abstract

Whole-genome sequencing (WGS) can improve assessment of low-frequency and rare variants, particularly in non-European populations that have been underrepresented in existing genomic studies. The genetic determinants of C-reactive protein (CRP), a biomarker of chronic inflammation, have been extensively studied, with existing genome-wide association studies (GWASs) conducted in >200,000 individuals of European ancestry. In order to discover novel loci associated with CRP levels, we examined a multi-ancestry population (n = 23,279) with WGS (∼38× coverage) from the Trans-Omics for Precision Medicine (TOPMed) program. We found evidence for eight distinct associations at the CRP locus, including two variants that have not been identified previously (rs11265259 and rs181704186), both of which are non-coding and more common in individuals of African ancestry (∼10% and ∼1% minor allele frequency, respectively, and rare or monomorphic in 1000 Genomes populations of East Asian, South Asian, and European ancestry). We show that the minor (G) allele of rs181704186 is associated with lower CRP levels and decreased transcriptional activity and protein binding in vitro, providing a plausible molecular mechanism for this African ancestry-specific signal. The individuals homozygous for rs181704186-G have a mean CRP level of 0.23 mg/L, in contrast to individuals heterozygous for rs181704186 with mean CRP of 2.97 mg/L and major allele homozygotes with mean CRP of 4.11 mg/L. This study demonstrates the utility of WGS in multi-ethnic populations to drive discovery of complex trait associations of large effect and to identify functional alleles in noncoding regulatory regions.

Indexed as

Genetic Predisposition to DiseasePolymorphism, Single NucleotideAsian PeopleBlack PeopleCohort StudiesC-Reactive ProteinGene FrequencyGenome-Wide Association StudyHumansLinkage DisequilibriumWhite PeopleWhole Genome SequencingC-Reactive Proteinc-reactive proteinwhole-genome sequencing

Identifiers

PMID31883642
PMCPMC7042494

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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.