Evidence map›Paper›PMID 34005834›Full record

SynthesisHuman mutation2021

Genetic pleiotropy of ERCC6 loss-of-function and deleterious missense variants links retinal dystrophy, arrhythmia, and immunodeficiency in diverse ancestries.

Iain S Forrest, Kumardeep Chaudhary, Ha My T Vy, Shantanu Bafna, Soyeon Kim, Hong-Hee Won, Ruth J F Loos, Judy Cho, Louis R Pasquale, Girish N Nadkarni and 2 more

Open access · greenAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Human mutation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 30% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Review
  3. 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

12 authors at 4 institutions in 2 countries.

Iain S ForrestCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.ORCID 0000-0002-5642-422X
Kumardeep ChaudharyCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Ha My T VyCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Shantanu BafnaCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Soyeon KimCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Hong-Hee WonSamsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea.
Ruth J F LoosCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Judy ChoCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Louis R PasqualeDepartment of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Girish N NadkarniCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Ghislain RocheleauCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Ron DoCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.ORCID 0000-0002-3144-3627
Icahn School of Medicine at Mount Sinai · USSamsung Medical Center · KRChild Health and Development Institute · USNew York Eye and Ear Infirmary · US

Funding

MOUNT SINAI MEDICAL SCIENTIST TRAINING PROGRAMT32GM007280 · NIGMS · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI BARON, MARGARET H · 1985 to 2021
$22.8M
Gene-Environment Interactions in GlaucomaR01EY015473 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI PASQUALE, LOUIS ROBERT · 2005 to 2021
$8.3M
Towards an integrated map of causal connections for common, complex diseasesR35GM124836 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ron Do · 2017 to 2026
$3.9M
Elucidating hereditary transthyretin-mediated heart failure risk using machine learning, polygenic risk and recall by genotype approaches in African ancestry individualsR01HL155915 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DO, RON, NADKARNI, GIRISH NITIN · 2021 to 2024
$3.4M
Big Omics Data Engine 2 SupercomputerS10OD026880 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2019 to 2019
$2.0M
Transforming Genomics with 5 PB Big Omics Data Engine Cray CS300-AC SupercomputerS10OD018522 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2014 to 2014
$1.9M
Resolving Causal Influences Among Correlated Risk Biomarkers for Coronary Artery DiseaseR01HL139865 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DO, RON · 2018 to 2021
$1.7M
Medical Research Council MC_PC_17228Medical Research Council MC_QA137853NEI NIH HHS R01 EY015473NHLBI NIH HHS R01 HL139865NHLBI NIH HHS R01 HL155915NIGMS NIH HHS R35 GM124836NIGMS NIH HHS T32 GM007280NIH HHS S10 OD018522NIH HHS S10 OD026880
6 · The paper itself

Abstract

Biobanks with exomes linked to electronic health records (EHRs) enable the study of genetic pleiotropy between rare variants and seemingly disparate diseases. We performed robust clinical phenotyping of rare, putatively deleterious variants (loss-of-function [LoF] and deleterious missense variants) in ERCC6, a gene implicated in inherited retinal disease. We analyzed 213,084 exomes, along with a targeted set of retinal, cardiac, and immune phenotypes from two large-scale EHR-linked biobanks. In the primary analysis, a burden of deleterious variants in ERCC6 was strongly associated with (1) retinal disorders; (2) cardiac and electrocardiogram perturbations; and (3) immunodeficiency and decreased immunoglobulin levels. Meta-analysis of results from the BioMe Biobank and UK Biobank showed a significant association of deleterious ERCC6 burden with retinal dystrophy (odds ratio [OR] = 2.6, 95% confidence interval [CI]: 1.5-4.6; p = 8.7 × 10

Indexed as

Genetic PleiotropyRetinal DystrophiesArrhythmias, CardiacDNA HelicasesDNA Repair EnzymesExomeExome SequencingHumansPoly-ADP-Ribose Binding ProteinsDNA HelicasesDNA Repair EnzymesERCC6 protein, humanPoly-ADP-Ribose Binding ProteinsERCC6genotype-first diagnosispleiotropyrare variantwhole-exome sequencing

Identifiers

PMID34005834
PMCPMC8295228
OpenAlexW3160647417

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.