ArticleFrontiers in genetics2014
Phenome-wide association study (PheWAS) in EMR-linked pediatric cohorts, genetically links PLCL1 to speech language development and IL5-IL13 to Eosinophilic Esophagitis.
Article in Frontiers in genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Replication and meta-analyses nominate numerous eosinophilic esophagitis risk genes.The Journal of allergy and clinical immunology · 2021Pooled it
- Multitrait analysis of genome-wide association studies expands eosinophilic esophagitis genetic susceptibility and polygenic risk scores.The Journal of allergy and clinical immunology · 2026Article
- Unravelling the pathogenesis of Eosinophilic Esophagitis from genetic predisposition to environmental triggers.Clinical and experimental immunology · 2025Review
- Uncovering Important Diagnostic Features for Alzheimer's, Parkinson's and Other Dementias Using Interpretable Association Mining Methods.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2025Article
- Genome-wide association study and polygenic risk scores of eosinophilia in Taiwan.Clinical & translational immunology · 2025Article
- Eosinophilic Esophagitis and Inflammatory Bowel Disease: What Are the Differences?International journal of molecular sciences · 2024Review
- Breaking down the complex pathophysiology of eosinophilic esophagitis.Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2023Review
- Language abnormalities in schizophrenia: binding core symptoms through contemporary empirical evidence.Schizophrenia (Heidelberg, Germany) · 2022Review
- KnockoffTrio: A knockoff framework for the identification of putative causal variants in genome-wide association studies with trio design.American journal of human genetics · 2022Article
- Large-scale real-world data analysis identifies comorbidity patterns in schizophrenia.Translational psychiatry · 2022Observational
- Peripheral Expression ofPsychiatry and clinical psychopharmacology · 2021Article
- Bidirectional crosstalk between eosinophils and esophageal epithelial cells regulates inflammatory and remodeling processes.Mucosal immunology · 2021Article
- GABA Signaling Pathway-associated Gene PLCL1 Rare Variants May be Associated with Autism Spectrum Disorders.Neuroscience bulletin · 2021Article
- Identifying developmental stuttering and associated comorbidities in electronic health records and creating a phenome risk classifier.Journal of fluency disorders · 2021Article
- Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets.Frontiers in physiology · 2021Review
- The genetic etiology of eosinophilic esophagitis.The Journal of allergy and clinical immunology · 2020Review
- Building a Population Representative Pediatric Biobank: Lessons Learned From the Greater Cincinnati Childhood Cohort.Frontiers in public health · 2020Article
- The current state of omics technologies in the clinical management of asthma and allergic diseases.Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2019Review
- Poly(ADP-Ribosylation) in Age-Related Neurological Disease.Trends in genetics : TIG · 2019Review
- Genetic variants at the 16p13 locus confer risk for eosinophilic esophagitis.Genes and immunity · 2019Article
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Authors and funding
16 authors at 7 institutions in 1 country.
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Abstract
objectiveWe report the first pediatric specific Phenome-Wide Association Study (PheWAS) using electronic medical records (EMRs). Given the early success of PheWAS in adult populations, we investigated the feasibility of this approach in pediatric cohorts in which associations between a previously known genetic variant and a wide range of clinical or physiological traits were evaluated. Although computationally intensive, this approach has potential to reveal disease mechanistic relationships between a variant and a network of phenotypes.
methodData on 5049 samples of European ancestry were obtained from the EMRs of two large academic centers in five different genotyped cohorts. Recently, these samples have undergone whole genome imputation. After standard quality controls, removing missing data and outliers based on principal components analyses (PCA), 4268 samples were used for the PheWAS study. We scanned for associations between 2476 single-nucleotide polymorphisms (SNP) with available genotyping data from previously published GWAS studies and 539 EMR-derived phenotypes. The false discovery rate was calculated and, for any new PheWAS findings, a permutation approach (with up to 1,000,000 trials) was implemented.
resultsThis PheWAS found a variety of common variants (MAF > 10%) with prior GWAS associations in our pediatric cohorts including Juvenile Rheumatoid Arthritis (JRA), Asthma, Autism and Pervasive Developmental Disorder (PDD) and Type 1 Diabetes with a false discovery rate < 0.05 and power of study above 80%. In addition, several new PheWAS findings were identified including a cluster of association near the NDFIP1 gene for mental retardation (best SNP rs10057309, p = 4.33 × 10(-7), OR = 1.70, 95%CI = 1.38 - 2.09); association near PLCL1 gene for developmental delays and speech disorder [best SNP rs1595825, p = 1.13 × 10(-8), OR = 0.65(0.57 - 0.76)]; a cluster of associations in the IL5-IL13 region with Eosinophilic Esophagitis (EoE) [best at rs12653750, p = 3.03 × 10(-9), OR = 1.73 95%CI = (1.44 - 2.07)], previously implicated in asthma, allergy, and eosinophilia; and association of variants in GCKR and JAZF1 with allergic rhinitis in our pediatric cohorts [best SNP rs780093, p = 2.18 × 10(-5), OR = 1.39, 95%CI = (1.19 - 1.61)], previously demonstrated in metabolic disease and diabetes in adults.
conclusionThe PheWAS approach with re-mapping ICD-9 structured codes for our European-origin pediatric cohorts, as with the previous adult studies, finds many previously reported associations as well as presents the discovery of associations with potentially important clinical implications.
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