ArticleAtherosclerosis2013
Association of SNPs in the UGT1A gene cluster with total bilirubin and mortality in the Diabetes Heart Study.
Article in Atherosclerosis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Genetic determinants of serum bilirubin using inferred native American gene variants in Chilean adolescents.Frontiers in genetics · 2024Article
- Genetics of Plasma Bilirubin and Associations between Bilirubin and Cardiometabolic Risk Profiles in Danish Children and Adolescents.Antioxidants (Basel, Switzerland) · 2023Article
- Mendelian randomization analyses support causal relationships between blood metabolites and the gut microbiome.Nature genetics · 2022Observational
- Population Levels Assessment of the Distribution of Disease-Associated Variants With Emphasis on Armenians - A Machine Learning Approach.Frontiers in genetics · 2019Article
- Rare variants in drug target genes contributing to complex diseases, phenome-wide.Scientific reports · 2018Article
- The U-Shaped Association between Bilirubin and Diabetic Retinopathy Risk: A Five-Year Cohort Based on 5323 Male Diabetic Patients.Journal of diabetes research · 2018Article
- Identification of novel targets of diabetic nephropathy and PEDF peptide treatment using RNA-seq.BMC genomics · 2016Article
- Article
- Serum bilirubin concentration is modified by UGT1A1 haplotypes and influences risk of type-2 diabetes in the Norfolk Island genetic isolate.BMC genetics · 2015Article
- A Phenomic Scan of the Norfolk Island Genetic Isolate Identifies a Major Pleiotropic Effect Locus Associated with Metabolic and Renal Disorder Markers.PLoS genetics · 2015Article
- Genome-wide analysis of hepatic lipid content in extreme obesity.Acta diabetologica · 2015Article
- Phenome-wide Association Study Relating Pretreatment Laboratory Parameters With Human Genetic Variants in AIDS Clinical Trials Group Protocols.Open forum infectious diseases · 2015Article
- Analysis of common and coding variants with cardiovascular disease in the Diabetes Heart Study.Cardiovascular diabetology · 2014Article
- Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
objectiveA negative relationship between total bilirubin concentration (TBili) and CVD risk has been documented in a series of epidemiological studies. In addition, TBili is thought to be under strong genetic regulation via the UGT1A gene family, suggesting it may be a heritable CVD risk factor. However, few studies directly relate TBili-associated UGT1A variants to CVD severity or outcome. This study replicated the genetic association for TBili in the Diabetes Heart Study (DHS), and examined the relationships of TBili-associated SNPs with measures of subclinical CVD and mortality.
methodsThis investigation included 1220 self-described European American (EA) individuals from the DHS, a family-based study examining risk for macrovascular complications in type 2 diabetes (T2D). Genetic associations with TBili were examined using the Affymetrix Genome-wide Human SNP Array 5.0 and the Illumina Infinium Human Exome beadchip v1.0. Subsequent analyses assessed the relationships of the top TBili-associated SNPs with measures of vascular calcified plaque and mortality.
resultsA genome-wide association study detected 18 SNPs within the UGT1A gene family associated with TBili at p < 5 × 10(-8). The top hit was rs887829 (p = 8.67 × 10(-20)). There was no compelling evidence of association between the top TBili-associated SNPs and vascular calcified plaque (p = 0.05-0.88). There was, however, evidence of association with all-cause mortality (p = 0.0004-0.06), the top hit being rs2741034.
conclusionThese findings support a potential role for UGT1A genetic variants in risk for mortality in T2D. Further quantification of the extent of CVD risk conferred by UGT1A gene family variants in a high risk cohort with T2D is still required.
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