ArticleEuropean journal of epidemiology2017
The interaction between smoking and HLA genes in multiple sclerosis: replication and refinement.
Article in European journal of epidemiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- The HLA paradox across populations in multiple sclerosis progression: a systematic review.BMC neurology · 2026Pooled it
- Reducing Early-Life Smoke Exposure as a Preventive Strategy for Pediatric Multiple Sclerosis: Results from the PEDIGREE Study.Neurology and therapy · 2026Article
- HLA polymorphism in neuroimmune diseases: linking antigen presentation to neuroinflammatory programs.Frontiers in immunology · 2026Review
- Multiple sclerosis pathophysiology: a comprehensive review of genetic, environmental, and immunological drivers.Inflammopharmacology · 2025Review
- Applying a genetic risk score model to enhance prediction of future multiple sclerosis diagnosis at first presentation with optic neuritis.Nature communications · 2024Article
- Review
- FutureMS cohort profile: a Scottish multicentre inception cohort study of relapsing-remitting multiple sclerosis.BMJ open · 2022Observational
- Risk Factors from Pregnancy to Adulthood in Multiple Sclerosis Outcome.International journal of molecular sciences · 2022Review
- Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target.Frontiers in immunology · 2022Review
- Association between HLA alleles and Epstein-Barr virus Zta-IgA serological status in healthy males from southern China.The journal of gene medicine · 2021Article
- The increased risk of multiple sclerosis associated with HLA-DRB1*15:01 and smoking is modified by alcohol consumption.Scientific reports · 2021Article
- DRB1-environment interactions in multiple sclerosis etiology: results from two Swedish case-control studies.Journal of neurology, neurosurgery, and psychiatry · 2021Article
- Methylome and transcriptome signature of bronchoalveolar cells from multiple sclerosis patients in relation to smoking.Multiple sclerosis (Houndmills, Basingstoke, England) · 2021Article
- Mining Complex Genetic Patterns Conferring Multiple Sclerosis Risk.International journal of environmental research and public health · 2021Article
- Moving from two- to multi-way interactions among binary risk factors on the additive scale.Biostatistics & epidemiology · 2020Article
- Little evidence for an effect of smoking on multiple sclerosis risk: A Mendelian Randomization study.PLoS biology · 2020Article
- Article
- Review
- Smoking and Epstein-Barr virus infection in multiple sclerosis development.Scientific reports · 2020Article
- Environmental Influencers, MicroRNA, and Multiple Sclerosis.Journal of central nervous system disease · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 10 institutions in 6 countries.
Funding
Abstract
Interactions between environment and genetics may contribute to multiple sclerosis (MS) development. We investigated whether the previously observed interaction between smoking and HLA genotype in the Swedish population could be replicated, refined and extended to include other populations. We used six independent case-control studies from five different countries (Sweden, Denmark, Norway, Serbia, United States). A pooled analysis was performed for replication of previous observations (7190 cases, 8876 controls). Refined detailed analyses were carried out by combining the genetically similar populations from the Nordic studies (6265 cases, 8401 controls). In both the pooled analyses and in the combined Nordic material, interactions were observed between HLA-DRB*15 and absence of HLA-A*02 and between smoking and each of the genetic risk factors. Two way interactions were observed between each combination of the three variables, invariant over categories of the third. Further, there was also a three way interaction between the risk factors. The difference in MS risk between the extremes was considerable; smokers carrying HLA-DRB1*15 and lacking HLA-A*02 had a 13-fold increased risk compared with never smokers without these genetic risk factors (OR 12.7, 95% CI 10.8-14.9). The risk of MS associated with HLA genotypes is strongly influenced by smoking status and vice versa. Since the function of HLA molecules is to present peptide antigens to T cells, the demonstrated interactions strongly suggest that smoking alters MS risk through actions on adaptive immunity.
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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.