ArticlePLoS genetics2019
MR-pheWAS with stratification and interaction: Searching for the causal effects of smoking heaviness identified an effect on facial aging.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 84 citations in OpenAlex.
- Systematic review of Mendelian randomization studies on risk of cancer.BMC medicine · 2022Pooled it
- Using Mendelian randomization analysis to better understand the relationship between mental health and substance use: a systematic review.Psychological medicine · 2021Pooled it
- A phenome-wide association study of genetically determined nicotine metabolism reveals novel links with health-related outcomes.European journal of epidemiology · 2025Article
- A hypothesis-free approach to identifying potential effects of relative age in school year: an instrumental variable phenome-wide association study in the UK Biobank.American journal of epidemiology · 2025Article
- Exploring pleiotropy in Mendelian randomisation analyses: What are genetic variants associated with 'cigarette smoking initiation' really capturing?Genetic epidemiology · 2025Article
- Mendelian Randomization Analysis of the Causal Effect of Cigarette Smoking on Hospital Costs.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024Article
- The association of psychological and trauma-related factors with biological and facial aging acceleration: evidence from the UK Biobank.BMC medicine · 2024Article
- Exploring the Bidirectional Causal Pathways Between Smoking Behaviors and Headache: A Mendelian Randomization Study.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024Article
- Socioeconomic traits and the risk of Barrett's esophagus and gastroesophageal reflux disease: A Mendelian randomization study.World journal of gastrointestinal oncology · 2024Article
- Different effects of 24 dietary intakes on gastroesophageal reflux disease: A mendelian randomization.World journal of clinical cases · 2024Article
- A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals.EBioMedicine · 2024Article
- Iron status and sarcopenia-related traits: a bi-directional Mendelian randomization study.Scientific reports · 2024Article
- Article
- The relationship between emotional disorders and heart rate variability: A Mendelian randomization study.PloS one · 2024Article
- Proxy gene-by-environment Mendelian randomization study of the association between cigarette smoking during pregnancy and offspring mental health.International journal of epidemiology · 2023Article
- Association between adiposity and facial aging: results from a Mendelian randomization study.European journal of medical research · 2023Article
- Evaluation for causal effects of socioeconomic traits on risk of female genital prolapse (FGP): a multivariable Mendelian randomization analysis.BMC medical genomics · 2023Article
- Associations between health behaviours, fertility and reproductive outcomes: triangulation of evidence in the Norwegian Mother, Father and Child Cohort Study (MoBa).BMC medicine · 2023Article
- Effects of insomnia and non-vasomotor menopausal symptoms on coronary heart disease risk: a mendelian randomization study.Heliyon · 2023Article
- An integrated genome and phenome-wide association study approach to understanding Alzheimer's disease predisposition.Neurobiology of aging · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Mendelian randomization (MR) is an established approach to evaluate the effect of an exposure on an outcome. The gene-by-environment (GxE) study design can be used to determine whether the genetic instrument affects the outcome through pathways other than via the exposure of interest (horizontal pleiotropy). MR phenome-wide association studies (MR-pheWAS) search for the effects of an exposure, and can be conducted in UK Biobank using the PHESANT package. In this proof-of-principle study, we introduce the novel GxE MR-pheWAS approach, that combines MR-pheWAS with the use of GxE interactions. This method aims to identify the presence of effects of an exposure while simultaneously investigating horizontal pleiotropy. We systematically test for the presence of causal effects of smoking heaviness-stratifying on smoking status (ever versus never)-as an exemplar. If a genetic variant is associated with smoking heaviness (but not smoking initiation), and this variant affects an outcome (at least partially) via tobacco intake, we would expect the effect of the variant on the outcome to differ in ever versus never smokers. We used PHESANT to test for the presence of effects of smoking heaviness, instrumented by genetic variant rs16969968, among never and ever smokers respectively, in UK Biobank. We ranked results by the strength of interaction between ever and never smokers. We replicated previously established effects of smoking heaviness, including detrimental effects on lung function. Novel results included a detrimental effect of heavier smoking on facial aging. We have demonstrated how GxE MR-pheWAS can be used to identify potential effects of an exposure, while simultaneously assessing whether results may be biased by horizontal pleiotropy.
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Registered trials
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.