Evidence mapPaperPMID 41501544Full record

ArticleNature genetics2026

Protein-protein interactions shape trans-regulatory impact of genetic variation on protein expression and complex traits.

Jinghui Li, Yang I Li, Xuanyao Liu

Abstract read
In one paragraph

Article in Nature genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

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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

3 authors.

Jinghui LiDepartment of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL, USA.ORCID 0000-0002-4854-2613
Yang I LiDepartment of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL, USA.
Xuanyao LiuDepartment of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL, USA. xuanyao@uchicago.edu.ORCID 0000-0002-5955-6738

Funding

Statistical Methods to Study the Genetic Basis and Mechanisms of Trans Gene RegulationR35GM138084 · NIGMS · UNIVERSITY OF CHICAGO · PI LIU, XUANYAO · 2020 to 2024
$2.0M
Computational genomics approaches to study mechanisms and function of mRNA splicingR35GM153249 · NIGMS · UNIVERSITY OF CHICAGO · PI Yang Li · 2024 to 2026
$1.2M
NIGMS NIH HHS R35 GM138084NIGMS NIH HHS R35 GM153249U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM138084U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM153249
6 · The paper itself

Abstract

Most genetic variants influence complex traits by affecting gene regulation. Yet, despite comprehensive catalogs of molecular quantitative trait loci (QTLs), linking trait-associated variants to biological functions remains difficult. By re-analyzing large maps of protein QTLs (pQTLs), we found that genes with trans-pQTLs but no cis-pQTLs are under strong selective constraints and are particularly informative in interpreting genome-wide association study (GWAS) loci. We observed that trans-pQTLs and their target proteins are frequently involved in protein-protein interactions (PPIs). Notably, trans-pQTLs are enriched in missense variants and at PPI interfaces, suggesting a key role of PPIs in the trans-regulation of proteome. Using PPI annotations to guide trans-pQTL mapping, we identified 17,662 trans-pQTLs affecting 961 PPI clusters after accounting for blood cell composition effects. These trans-pQTLs colocalized with 36% GWAS loci per trait on average for 27 complex traits, helping in many cases to link GWAS loci to cellular function. Finally, we identified trans-pQTL effects at multiple autoimmune GWAS loci that converge to the same PPIs, pinpointing protein complexes and signaling pathways that show promising therapeutic target potential.

Indexed as

Gene Expression RegulationGenetic VariationMultifactorial InheritanceProtein Interaction MapsQuantitative Trait LociGenome-Wide Association StudyHumansPolymorphism, Single NucleotideProtein Interaction Mapping

Identifiers

PMID41501544
PMCPMC12807863

What Socratic holds

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Registered trials

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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 Socratic graph.