Systematic elucidation of genetic mechanisms underlying cholesterol uptake.
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
10 Jan 2023
10 Jan 2023
Historique:
entrez:
30
1
2023
pubmed:
31
1
2023
medline:
31
1
2023
Statut:
epublish
Résumé
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
Identifiants
pubmed: 36711952
doi: 10.1101/2023.01.09.500804
pmc: PMC9881906
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : R01 HG010372
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL164409
Pays : United States
Commentaires et corrections
Type : UpdateIn
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