Evidence map›Paper›PMID 39142284›Full record

ArticleCell genomics2024

Genetic and functional analysis of Raynaud's syndrome implicates loci in vasculature and immunity.

Anniina Tervi, Markus Ramste, Erik Abner, Paul Cheng, Jacqueline M Lane, Matthew Maher, Jesse Valliere, Vilma Lammi, Satu Strausz, Juha Riikonen and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. 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

30 authors.

Anniina TerviInstitute for Molecular Medicine Finland, FIMM, Helsinki Institute of Life Science - HiLIFE, University of Helsinki, Helsinki, Finland. Electronic address: anniina.tervi@helsinki.fi.
Markus RamsteDivision of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Erik AbnerInstitute of Genomics, University of Tartu, Tartu, Estonia.
Paul ChengDivision of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jacqueline M LaneDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Matthew MaherCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jesse ValliereCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Vilma LammiInstitute for Molecular Medicine Finland, FIMM, Helsinki Institute of Life Science - HiLIFE, University of Helsinki, Helsinki, Finland.
Satu StrauszInstitute for Molecular Medicine Finland, FIMM, Helsinki Institute of Life Science - HiLIFE, University of Helsinki, Helsinki, Finland.
Juha RiikonenInstitute for Molecular Medicine Finland, FIMM, Helsinki Institute of Life Science - HiLIFE, University of Helsinki, Helsinki, Finland.
Trieu NguyenDivision of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Gabriella E MartynDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA; Basic Science and Engineering Initiative, Stanford Children's Health, Betty Irene Moore Children's Heart Center, Stanford, CA, USA.
Maya U ShethDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA; Basic Science and Engineering Initiative, Stanford Children's Health, Betty Irene Moore Children's Heart Center, Stanford, CA, USA.
Fan XiaDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA; Basic Science and Engineering Initiative, Stanford Children's Health, Betty Irene Moore Children's Heart Center, Stanford, CA, USA.
Mauro Lago DocampoDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA; Stanford Children's Health Betty Irene Moore Children's Heart Center, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Wenduo GuDivision of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
FinnGen, Estonian Biobank research team
Tõnu EskoInstitute of Genomics, University of Tartu, Tartu, Estonia.
Richa SaxenaCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Matti PirinenInstitute for Molecular Medicine Finland, FIMM, Helsinki Institute of Life Science - HiLIFE, University of Helsinki, Helsinki, Finland; Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland; Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Aarno PalotieInstitute for Molecular Medicine Finland, FIMM, Helsinki Institute of Life Science - HiLIFE, University of Helsinki, Helsinki, Finland; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Samuli RipattiInstitute for Molecular Medicine Finland, FIMM, Helsinki Institute of Life Science - HiLIFE, University of Helsinki, Helsinki, Finland; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Nasa Sinnott-ArmstrongHerbold Computational Biology Program, Public Health Sciences Division, Fred Hutch, Seattle, WA, USA.
Mark DalyInstitute for Molecular Medicine Finland, FIMM, Helsinki Institute of Life Science - HiLIFE, University of Helsinki, Helsinki, Finland; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jesse M EngreitzDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA; Basic Science and Engineering Initiative, Stanford Children's Health, Betty Irene Moore Children's Heart Center, Stanford, CA, USA; The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
Marlene RabinovitchStanford Children's Health Betty Irene Moore Children's Heart Center, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Caroline A HeckmanInstitute for Molecular Medicine Finland, FIMM, Helsinki Institute of Life Science - HiLIFE, University of Helsinki, Helsinki, Finland.
Thomas QuertermousDivision of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Samuel E JonesInstitute for Molecular Medicine Finland, FIMM, Helsinki Institute of Life Science - HiLIFE, University of Helsinki, Helsinki, Finland.
Hanna M OllilaInstitute for Molecular Medicine Finland, FIMM, Helsinki Institute of Life Science - HiLIFE, University of Helsinki, Helsinki, Finland; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: hanna.m.ollila@helsinki.fi.

Funding

Stanford Center for Connecting DNA Variants to Function and PhenotypeUM1HG011972 · NHGRI · STANFORD UNIVERSITY · PI JESSE M ENGREITZ, THOMAS QUERTERMOUS · 2021 to 2026
$10.5M
Endothelial Injury, BMPR2 Dysfunction and Macrophage Activation Cause EndMT and PAHR01HL138473 · NHLBI · STANFORD UNIVERSITY · PI Mark Robert Nicolls, Marlene Rabinovitch · 2017 to 2026
$4.9M
Mapping, modeling, and manipulating 3D contacts in vascular cells to connect risk variants to disease genesR01HL159176 · NHLBI · STANFORD UNIVERSITY · PI ENGREITZ, JESSE M · 2022 to 2025
$2.8M
Long COVID as a putative subtype of chronic fatigue syndromeR01AI170850 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Richa Saxena · 2022 to 2026
$2.2M
Systematic mapping and prediction of gene-enhancer connectionsR00HG009917 · NHGRI · STANFORD UNIVERSITY · PI ENGREITZ, JESSE M · 2020 to 2022
$796k
Systematic mapping and prediction of gene-enhancer connectionsK99HG009917 · NHGRI · BROAD INSTITUTE, INC. · PI ENGREITZ, JESSE M · 2018 to 2019
$65k
NHGRI NIH HHS K99 HG009917NHGRI NIH HHS R00 HG009917NHGRI NIH HHS UM1 HG011972NHLBI NIH HHS R01 HL138473NHLBI NIH HHS R01 HL159176NIAID NIH HHS R01 AI170850
6 · The paper itself

Abstract

Raynaud's syndrome is a dysautonomia where exposure to cold causes vasoconstriction and hypoxia, particularly in the extremities. We performed meta-analysis in four cohorts and discovered eight loci (ADRA2A, IRX1, NOS3, ACVR2A, TMEM51, PCDH10-DT, HLA, and RAB6C) where ADRA2A, ACVR2A, NOS3, TMEM51, and IRX1 co-localized with expression quantitative trait loci (eQTLs), particularly in distal arteries. CRISPR gene editing further showed that ADRA2A and NOS3 loci modified gene expression and in situ RNAscope clarified the specificity of ADRA2A in small vessels and IRX1 around small capillaries in the skin. A functional contraction assay in the cold showed lower contraction in ADRA2A-deficient and higher contraction in ADRA2A-overexpressing smooth muscle cells. Overall, our study highlights the power of genome-wide association testing with functional follow-up as a method to understand complex diseases. The results indicate temperature-dependent adrenergic signaling through ADRA2A, effects at the microvasculature by IRX1, endothelial signaling by NOS3, and immune mechanisms by the HLA locus in Raynaud's syndrome.

Indexed as

Genome-Wide Association StudyQuantitative Trait LociRaynaud DiseaseFemaleHumansMaleNitric Oxide Synthase Type IIINitric Oxide Synthase Type III

Identifiers

PMID39142284
PMCPMC11480858

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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.