scholarly journals Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations

Diabetes Care ◽  
2020 ◽  
Vol 44 (1) ◽  
pp. 98-106
Author(s):  
Ju-Sheng Zheng ◽  
Jian’an Luan ◽  
Eleni Sofianopoulou ◽  
Fumiaki Imamura ◽  
Isobel D. Stewart ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vitamin C ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Genome Wide Association ◽  
Plasma Vitamin ◽  
Genome Wide ◽  
Randomization Analysis ◽  
European Populations

scholarly journals Plasma vitamin C and type 2 diabetes: genome-wide association study and Mendelian randomization analysis in European populations

2020 ◽  
Author(s):  
Ju-Sheng Zheng ◽  
Jian’an Luan ◽  
Eleni Sofianopoulou ◽  
Fumiaki Imamura ◽  
Isobel D Stewart ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vitamin C ◽  
Mendelian Randomization ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Plasma Vitamin ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
European Populations

<b>Objective</b> Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. <p><b>Research Design and Methods</b> We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted difference in plasma vitamin C with type 2 diabetes in up-to 80,983 cases and 842,909 non-cases. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 cases and 11,073 non-cases.</p> <p><b>Results</b> We identified 11 genomic regions associated with plasma vitamin C (p<5×10<sup>-8</sup>), with the strongest signal at <i>SLC23A1</i>, and 10 novel genetic loci including <i>SLC23A3</i>, <i>CHPT1</i>,<i> BCAS3</i>, <i>SNRPF</i>, <i>RER1</i>, <i>MAF</i>, <i>GSTA5</i>, <i>RGS14</i>, <i>AKT1</i> and <i>FADS1</i>. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per standard deviation, 0.88, 95%CI: 0.82, 0.94), <a>but there was no association between genetically predicted plasma vitamin C (excluding <i>FADS1</i> variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03, 95%CI: 0.96, 1.10)</a>. </p> <p><b>Conclusions</b> <a>These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of</a> vitamin C supplementation for type 2 diabetes prevention.</p>

scholarly journals Plasma vitamin C and type 2 diabetes: genome-wide association study and Mendelian randomization analysis in European populations

2020 ◽  
Author(s):  
Ju-Sheng Zheng ◽  
Jian’an Luan ◽  
Eleni Sofianopoulou ◽  
Fumiaki Imamura ◽  
Isobel D Stewart ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vitamin C ◽  
Mendelian Randomization ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Plasma Vitamin ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
European Populations

<b>Objective</b> Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. <p><b>Research Design and Methods</b> We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted difference in plasma vitamin C with type 2 diabetes in up-to 80,983 cases and 842,909 non-cases. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 cases and 11,073 non-cases.</p> <p><b>Results</b> We identified 11 genomic regions associated with plasma vitamin C (p<5×10<sup>-8</sup>), with the strongest signal at <i>SLC23A1</i>, and 10 novel genetic loci including <i>SLC23A3</i>, <i>CHPT1</i>,<i> BCAS3</i>, <i>SNRPF</i>, <i>RER1</i>, <i>MAF</i>, <i>GSTA5</i>, <i>RGS14</i>, <i>AKT1</i> and <i>FADS1</i>. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per standard deviation, 0.88, 95%CI: 0.82, 0.94), <a>but there was no association between genetically predicted plasma vitamin C (excluding <i>FADS1</i> variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03, 95%CI: 0.96, 1.10)</a>. </p> <p><b>Conclusions</b> <a>These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of</a> vitamin C supplementation for type 2 diabetes prevention.</p>

The First Genome-Wide Association Study (GWAS) for Type 2 Diabetes in Youth from the Progress in Diabetes Genetics in Youth (ProDiGY) Collaboration

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1703-P ◽  
Author(s):  
SHYLAJA SRINIVASAN ◽  
JENNIFER TODD ◽  
LING CHEN ◽  
JASMIN DIVERS ◽  
SAM GIDDING ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Diabetes Genetics ◽  
Diabetes In Youth

scholarly journals Genome-wide Association Study of Pancreatic Fat: The Multiethnic Cohort Adiposity Phenotype Study

2021 ◽  
Author(s):  
Samantha Streicher ◽  
Unhee Lim ◽  
S. Lani Park ◽  
Yuqing Li ◽  
Xin Sheng ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
American Population ◽  
Pancreatic Fat ◽  
Genome Wide ◽  
Multiethnic Cohort

Several studies have found associations between higher pancreatic fat content and adverse health outcomes, such as diabetes and the metabolic syndrome, but investigations into the genetic contributions to pancreatic fat are limited.  This genome-wide association study, comprised of 804 participants with MRI-assessed pancreatic fat measurements, was conducted in the ethnically diverse Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS).  Two genetic variants reaching genome-wide significance, rs73449607 on chromosome 13q21.2 (Beta = -0.67, P = 4.50x10 -8 ) and rs7996760 on chromosome 6q14 (Beta = -0.90, P = 4.91x10 -8 ) were associated with percent pancreatic fat on the log scale.  Rs73449607 was most common in the African American population (13%) and rs79967607 was most common in the European American population (6%).  Rs73449607 was also suggestively associated with lower risk of type 2 diabetes (OR = 0.95, 95% CI = 0.89-1.00, P = 0.047) in the Population Architecture Genomics and Epidemiology (PAGE) Study and the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM), which included substantial numbers of non-European ancestry participants (53,102 cases and 193,679 controls).  Rs73449607 is located in an intergenic region between GSX1 and PLUT , and rs79967607 is in intron 1 of EPM2A .  PLUT, a linkRNA, regulates transcription of an adjacent gene, PDX1 , that controls beta-cell function in the mature pancreas, and EPM2A encodes the protein laforin, which plays a critical role in regulating glycogen production.  If validated, these variants may suggest a genetic component for pancreatic fat and a common etiologic link between pancreatic fat and type 2 diabetes.

scholarly journals Genome-Wide Association Study Identifies a Novel Locus Contributing to Type 2 Diabetes Susceptibility in Sikhs of Punjabi Origin From India

Diabetes ◽  
2013 ◽  
Vol 62 (5) ◽  
pp. 1746-1755 ◽  
Author(s):  
R. Saxena ◽  
D. Saleheen ◽  
L. F. Been ◽  
M. L. Garavito ◽  
T. Braun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Diabetes Susceptibility ◽  
Genome Wide

Pilot genome-wide association study identifying novel risk loci for type 2 diabetes in a Maya population

Gene ◽  
2018 ◽  
Vol 677 ◽  
pp. 324-331 ◽  
Author(s):  
Miriam Givisay Domínguez-Cruz ◽  
María de Lourdes Muñoz ◽  
Armando Totomoch-Serra ◽  
María Guadalupe García-Escalante ◽  
Juan Burgueño ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide

scholarly journals A Genome-Wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility Variants

Science ◽  
2007 ◽  
Vol 316 (5829) ◽  
pp. 1341-1345 ◽  
Author(s):  
L. J. Scott ◽  
K. L. Mohlke ◽  
L. L. Bonnycastle ◽  
C. J. Willer ◽  
Y. Li ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome
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