Evidence map›Paper›PMID 36711952›Full record

ArticlebioRxiv : the preprint server for biology2023

Systematic elucidation of genetic mechanisms underlying cholesterol uptake.

Marisa C Hamilton, James D Fife, Ersin Akinci, Tian Yu, Benyapa Khowpinitchai, Minsun Cha, Sammy Barkal, Thi Tun Thi, Grace H T Yeo, Juan Pablo Ramos Barroso and 7 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

17 authors at 4 institutions in 3 countries.

Marisa C HamiltonDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
James D FifeDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Ersin AkinciDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Tian YuDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Benyapa KhowpinitchaiDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Minsun ChaDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Sammy BarkalDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Thi Tun ThiPrecision Medicine Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Grace H T YeoDepartment of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Juan Pablo Ramos BarrosoDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Matthew Jake FrancoeurDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Minja VelimirovicDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
David K GiffordDepartment of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Guillaume LettreMontreal Heart Institute, Montréal, Québec, H1T 1C8, Canada.
Haojie YuPrecision Medicine Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Christopher A CassaDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Richard I SherwoodDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Brigham and Women's Hospital · USMassachusetts Institute of Technology · USNational University of Singapore · SGMontreal Heart Institute · CA

Funding

Integrated pathogenicity assessment of clinically actionable genetic variantsR01HG010372 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI CASSA, CHRISTOPHER · 2018 to 2022
$3.5M
High-throughput investigation of human genetic variants affecting cholesterol uptake and effluxR01HL164409 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SHERWOOD, RICHARD I · 2022 to 2025
$3.1M
High-Throughput Native Context Mapping and Modeling of Regulatory DNAR01HG008754 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GIFFORD, DAVID K · 2016 to 2019
$2.7M
Urgent Supplement: Correcting genetic disorders using predictable CRISPR/Cas9-induced exon skippingR21HG010391 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI CASSA, CHRISTOPHER, SHERWOOD, RICHARD I · 2019 to 2020
$632k
Medical Research Council MC_PC_17228NHGRI NIH HHS R01 HG008754NHGRI NIH HHS R01 HG010372NHGRI NIH HHS R21 HG010391NHLBI NIH HHS R01 HL164409
6 · The paper itself

Abstract

Genetic variation contributes greatly to LDL cholesterol (LDL-C) levels and coronary artery disease risk. By combining analysis of rare coding variants from the UK Biobank and genome-scale CRISPR-Cas9 knockout and activation screening, we have substantially improved the identification of genes whose disruption alters serum LDL-C levels. We identify 21 genes in which rare coding variants significantly alter LDL-C levels at least partially through altered LDL-C uptake. We use co-essentiality-based gene module analysis to show that dysfunction of the RAB10 vesicle transport pathway leads to hypercholesterolemia in humans and mice by impairing surface LDL receptor levels. Further, we demonstrate that loss of function of

Identifiers

PMID36711952
PMCPMC9881906
OpenAlexW4315489314

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.