ArticleCytokine2014
Novel gene variants predict serum levels of the cytokines IL-18 and IL-1ra in older adults.
Article in Cytokine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
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Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Soluble CD14-associated DNA methylation sites predict mortality among men with HIV infection.AIDS (London, England) · 2022Pooled it
- Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.Nature communications · 2019Pooled it
- Assessment of Inflammatory Biomarkers and Incident Atrial Fibrillation in Older Adults.Journal of the American Heart Association · 2024Article
- Genetic evidence for causal effects of immune dysfunction in psychiatric disorders: where are we?Translational psychiatry · 2024Review
- Genetic Markers of Insulin Resistance and Atherosclerosis in Type 2 Diabetes Mellitus Patients with Coronary Artery Disease.Metabolites · 2023Review
- Interleukin-1 receptor antagonist, mode of analgesia and risk of Caesarean delivery after onset of labour: a Mendelian randomisation analysis.British journal of anaesthesia · 2022Article
- Article
- Circulating biomarkers of immunity and inflammation, risk of Alzheimer's disease, and hippocampal volume: a Mendelian randomization study.Translational psychiatry · 2021Article
- Inflammasome genetics and complex diseases: a comprehensive review.European journal of human genetics : EJHG · 2020Review
- Multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults.Genome medicine · 2020Article
- Interleukin 1 receptor antagonist (Annals of the rheumatic diseases · 2020Article
- Combining Host Genetics and Functional Analysis to Depict Inflammasome Contribution in Tuberculosis Susceptibility and Outcome in Endemic Areas.Frontiers in immunology · 2020Article
- A Mendelian Randomization Analysis to Expose the Causal Effect of IL-18 on Osteoporosis Based on Genome-Wide Association Study Data.Frontiers in bioengineering and biotechnology · 2020Article
- Multivariate Genome-wide Association Analysis of a Cytokine Network Reveals Variants with Widespread Immune, Haematological, and Cardiometabolic Pleiotropy.American journal of human genetics · 2019Article
- Integrating Mendelian randomization and multiple-trait colocalization to uncover cell-specific inflammatory drivers of autoimmune and atopic disease.Human molecular genetics · 2019Article
- The Effect of Genetic Variation on the Placental Transcriptome in Humans.Frontiers in genetics · 2019Article
- A Positive Causal Influence of IL-18 Levels on the Risk of T2DM: A Mendelian Randomization Study.Frontiers in genetics · 2019Article
- Systemic inflammation and causal risk for Alzheimer's dementia: Possibilities and limitations of a Mendelian randomization approach.Aging medicine (Milton (N.S.W)) · 2018Article
- Inflammatory Biomarkers and Risk of Schizophrenia: A 2-Sample Mendelian Randomization Study.JAMA psychiatry · 2017Article
- Mendelian randomization: a novel approach for the prediction of adverse drug events and drug repurposing opportunities.International journal of epidemiology · 2017Article
Corrections and comments
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Authors and funding
16 authors at 9 institutions in 3 countries.
Funding
Abstract
Activation of inflammatory pathways measured by serum inflammatory markers such as interleukin-18 (IL-18) and interleukin-1 receptor antagonist (IL-1ra) is strongly associated with the progression of chronic disease states in older adults. Given that these serum cytokine levels are in part a heritable trait, genetic variation may predict increased serum levels. Using the Cardiovascular Health Study and InCHIANTI cohorts, a genome-wide association study was performed to identify genetic variants that influence IL-18 and IL-1ra serum levels among older adults. Multiple linear regression models characterized the association between each SNP and log-transformed cytokine values. Tests for multiple independent signals within statistically significant loci were performed using haplotype analysis and regression models conditional on lead SNP in each region. Multiple SNPs were associated with these cytokines with genome-wide significance, including SNPs in the IL-18-BCO gene region of chromosome 2 for IL-18 (top SNP rs2250417, P=1.9×10(-32)) and in the IL-1 gene family region of chromosome 2 for IL-1ra (rs6743376, P=2.3×10(-26)). Haplotype tests and conditional linear regression models showed evidence of multiple independent signals in these regions. Serum IL-18 levels were also associated with a region on chromosome 2 containing the NLRC4 gene (rs12989936, P=2.7×10(-19)). These data characterize multiple robust genetic signals that influence IL-18 and IL-1ra cytokine production. In particular, the signal for serum IL-18 located on chromosome two is novel and potentially important in inflammasome triggered chronic activation of inflammation in older adults. Replication in independent cohorts is an important next step, as well as molecular studies to better understand the role of NLRC4.
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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.