1703-P: Altered DNA-Methylation Modulates Adipose Tissue Gene Expression and Is Associated with Insulin Resistance in African Americans

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1703-P
Author(s):  
NEERAJ K. SHARMA ◽  
MARY E. COMEAU ◽  
CARL D. LANGEFELD ◽  
SWAPAN K. DAS
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
African Americans ◽  
Adipose Tissue Gene Expression ◽  
Tissue Gene Expression

scholarly journals Integrative analysis of glucometabolic traits, adipose tissue DNA methylation and gene expression identifies epigenetic regulatory mechanisms of insulin resistance and obesity in African Americans

2020 ◽  
Author(s):  
Ada Admin ◽  
Neeraj K. Sharma ◽  
Mary E. Comeau ◽  
Dennis Montoya ◽  
Matteo Pellegrini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
African Americans ◽  
Association Studies ◽  
Regulation Of Gene Expression ◽  
Transcript Level ◽  
Matsuda Index

Decline in insulin sensitivity due to dysfunction of adipose tissue (AT) is one of the earliest pathogenic events in Type 2 Diabetes. We hypothesize that differential DNA methylation (DNAm) controls insulin sensitivity and obesity by modulating transcript expression in AT. Integrating AT DNAm profiles with transcript profile data measured in a cohort of 230 African Americans from AAGMEx cohort, we performed <i>cis</i>-expression quantitative trait methylation (<i>cis</i>-eQTM) analysis to identify epigenetic regulatory loci for glucometabolic trait-associated transcripts. We identified significantly associated CpG-regions for 82 transcripts (FDR-P<0.05). The strongest eQTM locus was observed for the proopiomelanocortin (<i>POMC</i>; r= -0.632, P= 4.70X10<sup>-27</sup>) gene. Epigenome-wide association studies (EWAS) further identified 155, 46, and 168 CpG regions associated (FDR-P <0.05) with Matsuda index, S<sub>I</sub> and BMI, respectively. Intersection of EWAS, transcript level to trait association, and eQTM results, followed by causal inference test identified significant eQTM loci for 23 genes that were also associated with Matsuda index, S<sub>I </sub>and/or BMI in EWAS. These associated genes include <i>FERMT3</i>, <i>ITGAM</i>, <i>ITGAX</i>, and <i>POMC</i>. In summary, applying an integrative multi-omics approach, our study provides evidence for DNAm-mediated regulation of gene expression at both previously identified and novel loci for many key AT transcripts influencing insulin resistance and obesity.

scholarly journals Integrative Analysis of Glucometabolic Traits, Adipose Tissue DNA Methylation, and Gene Expression Identifies Epigenetic Regulatory Mechanisms of Insulin Resistance and Obesity in African Americans

Diabetes ◽  
2020 ◽  
Vol 69 (12) ◽  
pp. 2779-2793
Author(s):  
Neeraj K. Sharma ◽  
Mary E. Comeau ◽  
Dennis Montoya ◽  
Matteo Pellegrini ◽  
Timothy D. Howard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
African Americans ◽  
Integrative Analysis ◽  
Regulatory Mechanisms

scholarly journals Integrative analysis of glucometabolic traits, adipose tissue DNA methylation and gene expression identifies epigenetic regulatory mechanisms of insulin resistance and obesity in African Americans

2020 ◽  
Author(s):  
Ada Admin ◽  
Neeraj K. Sharma ◽  
Mary E. Comeau ◽  
Dennis Montoya ◽  
Matteo Pellegrini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
African Americans ◽  
Association Studies ◽  
Regulation Of Gene Expression ◽  
Transcript Level ◽  
Matsuda Index

Decline in insulin sensitivity due to dysfunction of adipose tissue (AT) is one of the earliest pathogenic events in Type 2 Diabetes. We hypothesize that differential DNA methylation (DNAm) controls insulin sensitivity and obesity by modulating transcript expression in AT. Integrating AT DNAm profiles with transcript profile data measured in a cohort of 230 African Americans from AAGMEx cohort, we performed <i>cis</i>-expression quantitative trait methylation (<i>cis</i>-eQTM) analysis to identify epigenetic regulatory loci for glucometabolic trait-associated transcripts. We identified significantly associated CpG-regions for 82 transcripts (FDR-P<0.05). The strongest eQTM locus was observed for the proopiomelanocortin (<i>POMC</i>; r= -0.632, P= 4.70X10<sup>-27</sup>) gene. Epigenome-wide association studies (EWAS) further identified 155, 46, and 168 CpG regions associated (FDR-P <0.05) with Matsuda index, S<sub>I</sub> and BMI, respectively. Intersection of EWAS, transcript level to trait association, and eQTM results, followed by causal inference test identified significant eQTM loci for 23 genes that were also associated with Matsuda index, S<sub>I </sub>and/or BMI in EWAS. These associated genes include <i>FERMT3</i>, <i>ITGAM</i>, <i>ITGAX</i>, and <i>POMC</i>. In summary, applying an integrative multi-omics approach, our study provides evidence for DNAm-mediated regulation of gene expression at both previously identified and novel loci for many key AT transcripts influencing insulin resistance and obesity.

243-OR: Integrative Multiomics Analysis of Glucometabolic Traits, Adipose Tissue DNA Methylation, and Gene Expression Identifies Epigenetic Regulatory Mechanisms of Insulin Resistance and Obesity in African Americans

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 243-OR
Author(s):  
NEERAJ K. SHARMA ◽  
MARY COMEAU ◽  
DENNIS J. MONTOYA ◽  
MATTEO PELLEGRINI ◽  
TIMOTHY HOWARD ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
African Americans ◽  
Regulatory Mechanisms

Central obesity and altered peripheral adipose tissue gene expression characterize the NAFLD patient with insulin resistance: Role of nutrition and insulin challenge

Nutrition ◽  
2014 ◽  
Vol 30 (2) ◽  
pp. 177-185 ◽  
Author(s):  
J.A. Paniagua ◽  
J.M. Escandell-Morales ◽  
D. Gil-Contreras ◽  
F.J. Berral de la Rosa ◽  
M. Romero-Jimenez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Central Obesity ◽  
Nafld Patient ◽  
Adipose Tissue Gene Expression ◽  
Tissue Gene Expression

scholarly journals Differences in Muscle and Adipose Tissue Gene Expression and Cardio-Metabolic Risk Factors in the Members of Physical Activity Discordant Twin Pairs

PLoS ONE ◽  
2010 ◽  
Vol 5 (9) ◽  
pp. e12609 ◽  
Author(s):  
Tuija Leskinen ◽  
Rita Rinnankoski-Tuikka ◽  
Mirva Rintala ◽  
Tuulikki Seppänen-Laakso ◽  
Eija Pöllänen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Physical Activity ◽  
Risk Factors ◽  
Adipose Tissue ◽  
Metabolic Risk Factors ◽  
Metabolic Risk ◽  
Adipose Tissue Gene Expression ◽  
Tissue Gene Expression ◽  
Discordant Twin

Central injection of oxytocin reduces food intake and affects hypothalamic and adipose tissue gene expression in chickens

2019 ◽  
Vol 67 ◽  
pp. 11-20
Author(s):  
Betty R. McConn ◽  
Anna Koskinen ◽  
D. Michael Denbow ◽  
Elizabeth R. Gilbert ◽  
Paul B. Siegel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Food Intake ◽  
Adipose Tissue Gene Expression ◽  
Tissue Gene Expression
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