ArticleThe Journal of clinical endocrinology and metabolism2011
Type 2 diabetes (T2D) associated polymorphisms regulate expression of adjacent transcripts in transformed lymphocytes, adipose, and muscle from Caucasian and African-American subjects.
Article in The Journal of clinical endocrinology and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 22 citations in OpenAlex.
- Bridging the variant-to-function gap in type 2 diabetes: advances and challenges.Diabetologia · 2026Review
- Deletion ofProceedings of the National Academy of Sciences of the United States of America · 2022Article
- GWA-based pleiotropic analysis identified potential SNPs and genes related to type 2 diabetes and obesity.Journal of human genetics · 2021Article
- Expression Quantitative Trait Loci in Equine Skeletal Muscle Reveals Heritable Variation in Metabolism and the Training Responsive Transcriptome.Frontiers in genetics · 2019Article
- Improved detection of genetic loci in estimated glomerular filtration rate and type 2 diabetes using a pleiotropic cFDR method.Molecular genetics and genomics : MGG · 2018Article
- Tissue-Specific and Genetic Regulation of Insulin Sensitivity-Associated Transcripts in African Americans.The Journal of clinical endocrinology and metabolism · 2016Article
- Expression quantitative trait analyses to identify causal genetic variants for type 2 diabetes susceptibility.World journal of diabetes · 2014Review
- Allelic expression imbalance screening of genes in chromosome 1q21-24 region to identify functional variants for Type 2 diabetes susceptibility.Physiological genomics · 2013Article
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- Phospholipid biosynthesis genes and susceptibility to obesity: analysis of expression and polymorphisms.PloS one · 2013Article
- Nutritional regulation of genome-wide association obesity genes in a tissue-dependent manner.Nutrition & metabolism · 2012Article
- Single nucleotide polymorphisms in JAZF1 and BCL11A gene are nominally associated with type 2 diabetes in African-American families from the GENNID study.Journal of human genetics · 2012Article
- An integrative genomics approach identifies activation of thioredoxin/thioredoxin reductase-1-mediated oxidative stress defense pathway and inhibition of angiogenesis in obese nondiabetic human subjects.The Journal of clinical endocrinology and metabolism · 2011Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
contextGenome-wide association scans (GWAS) have identified novel single nucleotide polymorphisms (SNPs) that increase T2D susceptibility and indicated the role of nearby genes in T2D pathogenesis.
objectiveWe hypothesized that T2D-associated SNPs act as cis-regulators of nearby genes in human tissues and that expression of these transcripts may correlate with metabolic traits, including insulin sensitivity (S(I)). DESIGN, SETTINGS, AND PATIENTS: Association of SNPs with the expression of their nearest transcripts was tested in adipose and muscle from 168 healthy individuals who spanned a broad range of S(I) and body mass index (BMI) and in transformed lymphocytes (TLs). We tested correlations between the expression of these transcripts in adipose and muscle with metabolic traits. Utilizing allelic expression imbalance (AEI) analysis we examined the presence of other cis-regulators for those transcripts in TLs.
resultsSNP rs9472138 was significantly (P = 0.037) associated with the expression of VEGFA in TLs while rs6698181 was detected as a cis-regulator for the PKN2 in muscle (P = 0.00027) and adipose (P = 0.018). Significant association was also observed for rs17036101 (P = 0.001) with expression of SYN2 in adipose of Caucasians. Among 19 GWAS-implicated transcripts, expression of VEGFA in adipose was correlated with BMI (r = -0.305) and S(I) (r = 0.230). Although only a minority of the T2D-associated SNPs were validated as cis-eQTLs for nearby transcripts, AEI analysis indicated presence of other cis-regulatory polymorphisms in 54% of these transcripts.
conclusionsOur study suggests that a small subset of GWAS-identified SNPs may increase T2D susceptibility by modulating expression of nearby transcripts in adipose or muscle.
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