ArticleNature communications2021
Pairwise effects between lipid GWAS genes modulate lipid plasma levels and cellular uptake.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Functional genomic analysis reveals HAVCR1 as the key regulator of 5q33.3 locus linked to hyperlipidemia.HGG advances · 2026Article
- Interactions with polygenic background impact quantitative traits in the UK Biobank.medRxiv : the preprint server for health sciences · 2025Article
- Building a growing genomic repository for maternal and fetal health through the PING Consortium.Pediatric research · 2025Article
- Genetic analyses point to alterations in immune-related pathways underpinning the association between psychiatric disorders and COVID-19.Molecular psychiatry · 2025Article
- Transfer learning with false negative control improves polygenic risk prediction.PLoS genetics · 2023Article
- APOE ɛ4 allele and TOMM40-APOC1 variants jointly contribute to survival to older ages.Aging cell · 2022Article
- Regulation of the COPII secretory machinery via focal adhesions and extracellular matrix signaling.The Journal of cell biology · 2022Article
Corrections and comments
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Authors and funding
15 authors.
Funding
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Abstract
Complex traits are characterized by multiple genes and variants acting simultaneously on a phenotype. However, studying the contribution of individual pairs of genes to complex traits has been challenging since human genetics necessitates very large population sizes, while findings from model systems do not always translate to humans. Here, we combine genetics with combinatorial RNAi (coRNAi) to systematically test for pairwise additive effects (AEs) and genetic interactions (GIs) between 30 lipid genome-wide association studies (GWAS) genes. Gene-based burden tests from 240,970 exomes show that in carriers with truncating mutations in both, APOB and either PCSK9 or LPL ("human double knock-outs") plasma lipid levels change additively. Genetics and coRNAi identify overlapping AEs for 12 additional gene pairs. Overlapping GIs are observed for TOMM40/APOE with SORT1 and NCAN. Our study identifies distinct gene pairs that modulate plasma and cellular lipid levels primarily via AEs and nominates putative drug target pairs for improved lipid-lowering combination therapies.
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