ArticleHuman genetics2014
Unraveling the complex genetic model for cystic fibrosis: pleiotropic effects of modifier genes on early cystic fibrosis-related morbidities.
Article in Human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 3 of them syntheses 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
59 citing papers in PubMed, 3 syntheses or guidelines pooled it, 111 citations in OpenAlex.
- Impact of Gene Modifiers on Cystic Fibrosis Phenotypic Profiles: A Systematic Review.Human mutation · 2024Pooled it
- Pooled it
- Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis.Nature communications · 2015Pooled it
- Emerging roles of SLC6A14 in digestive system diseases: from amino acid transport to therapeutic targeting.Molecular biology reports · 2026Review
- Distinct regulatory elements of SLC6A14 expression contribute to modification of cystic fibrosis phenotypes.Human genetics · 2026Article
- Most Pleiotropic Effects of Gene Knockouts Are Evolutionarily Transient in Yeasts.Molecular biology and evolution · 2024Article
- Cystic fibrosis.Nature reviews. Disease primers · 2024Review
- Delayed identification of compound heterozygous (Phe508del/Arg117His) cystic fibrosis variants in a patient awaiting liver transplantation.BMJ case reports · 2023Article
- Modifier Factors of Cystic Fibrosis Phenotypes: A Focus on Modifier Genes.International journal of molecular sciences · 2022Review
- Bicarbonate Effects on Antibacterial Immunity and Mucus Glycobiology in the Cystic Fibrosis Lung: A Review With Selected Experimental Observations.Infectious microbes & diseases · 2022Article
- Factors Predisposing the Response to Lumacaftor/Ivacaftor in People with Cystic Fibrosis.Journal of personalized medicine · 2022Article
- SLC26A9 as a Potential Modifier and Therapeutic Target in Cystic Fibrosis Lung Disease.Biomolecules · 2022Review
- SLC6A14 Impacts Cystic Fibrosis Lung Disease SeverityFrontiers in molecular biosciences · 2022Article
- Genetic Modifying Factors of Cystic Fibrosis Phenotype: A Challenge for Modern Medicine.Journal of clinical medicine · 2021Review
- Synergy in Cystic Fibrosis Therapies: Targeting SLC26A9.International journal of molecular sciences · 2021Article
- SLC26A9 SNP rs7512462 is not associated with lung disease severity or lung function response to ivacaftor in cystic fibrosis patients with G551D-CFTR.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2021Observational
- Pancreatitis severity in mice with impaired CFTR function but pancreatic sufficiency is mediated via ductal and inflammatory cells-Not acinar cells.Journal of cellular and molecular medicine · 2021Article
- Cystic Fibrosis Lung Disease Modifiers and Their Relevance in the New Era of Precision Medicine.Genes · 2021Review
- These Are the Genes You're Looking For: Finding Host Resistance Genes.Trends in microbiology · 2021Review
- Airway Surface Liquid pH Regulation in Airway Epithelium Current Understandings and Gaps in Knowledge.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The existence of pleiotropy in disorders with multi-organ involvement can suggest therapeutic targets that could ameliorate overall disease severity. Here we assessed pleiotropy of modifier genes in cystic fibrosis (CF). CF, caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, affects the lungs, liver, pancreas and intestines. However, modifier genes contribute to variable disease severity across affected organs, even in individuals with the same CFTR genotype. We sought to determine whether SLC26A9, SLC9A3 and SLC6A14, that contribute to meconium ileus in CF, are pleiotropic for other early-affecting CF co-morbidities. In the Canadian CF population, we assessed evidence for pleiotropic effects on (1) pediatric lung disease severity (n = 815), (2) age at first acquisition of Pseudomonas aeruginosa (P. aeruginosa) (n = 730), and (3) prenatal pancreatic damage measured by immunoreactive trypsinogen (n = 126). A multiple-phenotype analytic strategy assessed evidence for pleiotropy in the presence of phenotypic correlation. We required the same alleles to be associated with detrimental effects. SLC26A9 was pleiotropic for meconium ileus and pancreatic damage (p = 0.002 at rs7512462), SLC9A3 for meconium ileus and lung disease (p = 1.5 × 10(-6) at rs17563161), and SLC6A14 for meconium ileus and both lung disease and age at first P. aeruginosa infection (p = 0.0002 and p = 0.006 at rs3788766, respectively). The meconium ileus risk alleles in SLC26A9, SLC9A3 and SLC6A14 are pleiotropic, increasing risk for other early CF co-morbidities. Furthermore, co-morbidities affecting the same organ tended to associate with the same genes. The existence of pleiotropy within this single disorder suggests that complementary therapeutic strategies to augment solute transport will benefit multiple CF-associated tissues.
Indexed as
Identifiers
What OpenQuestion holds
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.