Evidence map›Paper›PMID 40370099›Full record

ArticleBriefings in bioinformatics2025

Accounting for the impact of rare variants on causal inference with RARE: a novel multivariable Mendelian randomization method.

Yu Cheng, Xinjia Ruan, Xiaofan Lu, Yuqing Yang, Yuhang Wang, Shangjin Yan, Yuzhe Sun, Fangrong Yan, Liyun Jiang, Tiantian Liu

Abstract read
In one paragraph

Article in Briefings in bioinformatics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

10 authors.

Yu ChengResearch Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, #639 Longmian Ave, Jiangning District, Nanjing 211100, Jiangsu, China.
Xinjia RuanResearch Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, #639 Longmian Ave, Jiangning District, Nanjing 211100, Jiangsu, China.
Xiaofan LuDepartment of Cancer and Functional Genomics, Institute of Genetics and Molecular and Cellular Biology, CNRS/INSERM/UNISTRA, #10142 BP, Illkirch 67400, Bas-Rhin, France.
Yuqing YangResearch Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, #639 Longmian Ave, Jiangning District, Nanjing 211100, Jiangsu, China.
Yuhang WangResearch Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, #639 Longmian Ave, Jiangning District, Nanjing 211100, Jiangsu, China.
Shangjin YanHigh School Affiliated to Nanjing Normal University, #37 Chahar Road, Gulou District, Nanjing 210003, Jiangsu, China.
Yuzhe SunDepartment of Biochemistry, Vassar college, Poughkeepsie, NY 12604, United States.
Fangrong YanResearch Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, #639 Longmian Ave, Jiangning District, Nanjing 211100, Jiangsu, China.
Liyun JiangResearch Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, #639 Longmian Ave, Jiangning District, Nanjing 211100, Jiangsu, China.
Tiantian LiuResearch Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, #639 Longmian Ave, Jiangning District, Nanjing 211100, Jiangsu, China.

Funding

2024 National Key Research on Multi-Target Natural Drugs SKLNMZZ2024JS32Fundamental Research Funds for the Central Universities of China Pharmaceutical University 2632023FY04Fundamental Research Funds for the Central Universities of China Pharmaceutical University 2632023FY05Key Laboratory of Scientific and Engineering ComputingNational Natural Science Foundation of China 82273735National Natural Science Foundation of China 82304252National Natural Science Foundation of China 82473737National Science Foundation for Young Scientists of China 82404380Shanghai Frontiers Science Center of Modern Analysis
6 · The paper itself

Abstract

Mendelian randomization (MR) method utilizes genetic variants as instrumental variables to infer the causal effect of an exposure on an outcome. However, the impact of rare variants on traits is often neglected, and traditional MR assumptions can be violated by correlated horizontal pleiotropy (CHP) and uncorrelated horizontal pleiotropy (UHP). To address these issues, we propose a multivariable MR approach, an extension of the standard MR framework: MVMR incorporating Rare variants Accounting for multiple Risk factors and shared horizontal plEiotropy (RARE). In the simulation studies, we demonstrate that RARE effectively detects the causal effects of exposures on outcome with accounting for the impact of rare variants on causal inference. Additionally, we apply RARE to study the effects of high density lipoprotein and low density lipoprotein on type 2 diabetes and coronary atherosclerosis, respectively, thereby illustrating its robustness and effectiveness in real data analysis.

Indexed as

Genetic VariationMendelian Randomization AnalysisCausalityComputer SimulationCoronary Artery DiseaseDiabetes Mellitus, Type 2Genetic PleiotropyHumansLipoproteins, HDLLipoproteins, LDLPolymorphism, Single NucleotideRisk FactorsLipoproteins, HDLLipoproteins, LDLcoronary atherosclerosishorizontal pleiotropyMVMRpolygenic risk scoresrare variants

Identifiers

PMID40370099
PMCPMC12078940

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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 OpenQuestion graph.