ArticlePloS one2015
A GWAS Study on Liver Function Test Using eMERGE Network Participants.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Replication and Characterization of Association between ABO SNPs and Red Blood Cell Traits by Meta-Analysis in Europeans.PloS one · 2016Pooled it
- Effect of bilirubin and Gilbert syndrome on health: cohort analysis of observational, genetic, and Mendelian randomisation associations.BMJ medicine · 2023Article
- A comprehensive analysis of SNPs and CNVs identifies novel markers associated with disease outcomes in colorectal cancer.Molecular oncology · 2021Article
- A UGT1A1 variant is associated with serum total bilirubin levels, which are causal for hypertension in African-ancestry individuals.NPJ genomic medicine · 2021Article
- Article
- Building a Population Representative Pediatric Biobank: Lessons Learned From the Greater Cincinnati Childhood Cohort.Frontiers in public health · 2020Article
- The eMERGE genotype set of 83,717 subjects imputed to ~40 million variants genome wide and association with the herpes zoster medical record phenotype.Genetic epidemiology · 2019Article
- Article
- Secondary Use and Analysis of Big Data Collected for Patient Care.Yearbook of medical informatics · 2017Review
- Exploration of haplotype research consortium imputation for genome-wide association studies in 20,032 Generation Scotland participants.Genome medicine · 2017Article
- Phenome-Wide Association Studies as a Tool to Advance Precision Medicine.Annual review of genomics and human genetics · 2016Review
- Unravelling the human genome-phenome relationship using phenome-wide association studies.Nature reviews. Genetics · 2016Review
- Feasibility of Representing Data from Published Nursing Research Using the OMOP Common Data Model.AMIA ... Annual Symposium proceedings. AMIA Symposium · 2016Article
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16 authors at 10 institutions in 1 country.
Funding
Abstract
introductionLiver enzyme levels and total serum bilirubin are under genetic control and in recent years genome-wide population-based association studies have identified different susceptibility loci for these traits. We conducted a genome-wide association study in European ancestry participants from the Electronic Medical Records and Genomics (eMERGE) Network dataset of patient medical records with available genotyping data in order to identify genetic contributors to variability in serum bilirubin levels and other liver function tests and to compare the effects between adult and pediatric populations.
methodsThe process of whole genome imputation of eMERGE samples with standard quality control measures have been described previously. After removing missing data and outliers based on principal components (PC) analyses, 3294 samples from European ancestry were used for the GWAS study. The association between each single nucleotide polymorphism (SNP) and total serum bilirubin and other liver function tests was tested using linear regression, adjusting for age, gender, site, platform and ancestry principal components (PC).
resultsConsistent with previous results, a strong association signal has been detected for UGT1A gene cluster (best SNP rs887829, beta = 0.15, p = 1.30x10-118) for total serum bilirubin level. Indeed, in this region more than 176 SNPs (or indels) had p<10-8 spanning 150Kb on the long arm of chromosome 2q37.1. In addition, we found a similar level of magnitude in a pediatric group (p = 8.26x10-47, beta = 0.17). Further imputation using sequencing data as a reference panel revealed association of other markers including known TA7 repeat indels (rs8175347) (p = 9.78x10-117) and rs111741722 (p = 5.41x10-119) which were in proxy (r2 = 0.99) with rs887829. Among rare variants, two Asian subjects homozygous for coding SNP rs4148323 (G71R) were identified. Additional known effects for total serum bilirubin were also confirmed including organic anion transporters SLCO1B1-SLCO1B3, TDRP and ZMYND8 at FDR<0.05 with no gene-gene interaction effects. Phenome-wide association studies (PheWAS) suggest a protective effect of TA7 repeat against cerebrovascular disease in an adult cohort (OR = 0.75, p = 0.0008). Among other liver function tests, we also confirmed the previous effect of the ABO blood group locus for variation in serum alkaline phosphatase (rs579459, p = 9.44x10-15).
conclusionsTaken together, our data present interesting findings with strong confirmation of previous effects by simply using the eMERGE electronic health record phenotyping. In addition, our findings indicate that similar to the adult population, the UGT1A1 is the main locus responsible for normal variation of serum bilirubin in pediatric populations.
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