scholarly journals The First Genome-Wide Association Study for Type 2 Diabetes in Youth: The Progress in Diabetes Genetics in Youth (ProDiGY) Consortium

2021 ◽  
Author(s):  
Shylaja Srinivasan ◽  
Ling Chen ◽  
Jennifer Todd ◽  
Jasmin Divers ◽  
Samuel Gidding ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Linear Mixed Model ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Relationship Matrix ◽  
Onset Type ◽  
Genome Wide ◽  
Diabetes In Youth

The prevalence of type 2 diabetes in youth has increased substantially, yet the genetic underpinnings remain largely unexplored. To identify genetic variants predisposing to youth-onset type 2 diabetes, we formed ProDiGY, a multi-ethnic collaboration of three studies (TODAY, SEARCH, and T2D-GENES) with 3,006 youth type 2 diabetes cases (mean age 15.1±2.9 y) and 6,061 diabetes-free adult controls (mean age 54.2±12.4 y). After stratifying by principal component-clustered ethnicity, we performed association analyses on ~10 million imputed variants using a generalized linear mixed model incorporating a genetic relationship matrix to account for population structure and adjusting for sex. We identified 7 genome-wide significant loci, including the novel locus rs10992863 in <i>PHF2 </i>(<i>P</i>=3.2´10<sup>-8</sup>, odds ratio [OR]=1.23). Known loci identified in our analysis include rs7903146 in <i>TCF7L2 </i>(<i>P</i>=8.0´10<sup>-20</sup>, OR 1.58), rs72982988 near <i>MC4R </i>(<i>P</i>=4.4´10<sup>-14</sup>, OR=1.53), rs200893788 in <i>CDC123</i> (<i>P</i>=1.1´10<sup>-12</sup>, OR= 1.32), rs2237892 in <i>KCNQ1</i> (<i>P</i>=4.8´10<sup>-11</sup>, OR=1.59), rs937589119 in <i>IGF2BP2</i> (<i>P</i>=3.1´10<sup>-9</sup>, OR=1.34) and rs113748381 in <i>SLC16A11 </i>(<i>P</i>=4.1´10<sup>-8</sup>, OR=1.04). Secondary analysis with 856 diabetes-free youth controls uncovered an additional locus in <i>CPEB2</i> (<i>P</i>=3.2´10<sup>-8</sup>, OR=2.1) and consistent direction of effect for diabetes risk. In conclusion, we identified both known and novel loci in the first genome wide association study (GWAS) of youth-onset type 2 diabetes.

scholarly journals The First Genome-Wide Association Study for Type 2 Diabetes in Youth: The Progress in Diabetes Genetics in Youth (ProDiGY) Consortium

2021 ◽  
Author(s):  
Shylaja Srinivasan ◽  
Ling Chen ◽  
Jennifer Todd ◽  
Jasmin Divers ◽  
Samuel Gidding ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Linear Mixed Model ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Relationship Matrix ◽  
Onset Type ◽  
Genome Wide ◽  
Diabetes In Youth

The prevalence of type 2 diabetes in youth has increased substantially, yet the genetic underpinnings remain largely unexplored. To identify genetic variants predisposing to youth-onset type 2 diabetes, we formed ProDiGY, a multi-ethnic collaboration of three studies (TODAY, SEARCH, and T2D-GENES) with 3,006 youth type 2 diabetes cases (mean age 15.1±2.9 y) and 6,061 diabetes-free adult controls (mean age 54.2±12.4 y). After stratifying by principal component-clustered ethnicity, we performed association analyses on ~10 million imputed variants using a generalized linear mixed model incorporating a genetic relationship matrix to account for population structure and adjusting for sex. We identified 7 genome-wide significant loci, including the novel locus rs10992863 in <i>PHF2 </i>(<i>P</i>=3.2´10<sup>-8</sup>, odds ratio [OR]=1.23). Known loci identified in our analysis include rs7903146 in <i>TCF7L2 </i>(<i>P</i>=8.0´10<sup>-20</sup>, OR 1.58), rs72982988 near <i>MC4R </i>(<i>P</i>=4.4´10<sup>-14</sup>, OR=1.53), rs200893788 in <i>CDC123</i> (<i>P</i>=1.1´10<sup>-12</sup>, OR= 1.32), rs2237892 in <i>KCNQ1</i> (<i>P</i>=4.8´10<sup>-11</sup>, OR=1.59), rs937589119 in <i>IGF2BP2</i> (<i>P</i>=3.1´10<sup>-9</sup>, OR=1.34) and rs113748381 in <i>SLC16A11 </i>(<i>P</i>=4.1´10<sup>-8</sup>, OR=1.04). Secondary analysis with 856 diabetes-free youth controls uncovered an additional locus in <i>CPEB2</i> (<i>P</i>=3.2´10<sup>-8</sup>, OR=2.1) and consistent direction of effect for diabetes risk. In conclusion, we identified both known and novel loci in the first genome wide association study (GWAS) of youth-onset type 2 diabetes.

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 lipid traits in youth with type 2 diabetes

2021 ◽  
Author(s):  
Nicola Santoro ◽  
Ling Chen ◽  
Jennifer Todd ◽  
Jasmin Divers ◽  
Amy S Shah ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Risk Allele ◽  
Density Lipoprotein ◽  
Genome Wide Association ◽  
Relationship Matrix ◽  
Genome Wide ◽  
A Genome

Abstract Context Dyslipidemia is highly prevalent in youth with type 2 diabetes (T2D), yet the pathogenic components of dyslipidemia in youth with T2D are poorly understood. Objective To evaluate the genetic determinants of lipid traits in youth with T2D through a genome-wide association study (GWAS). Design, participants and main outcome measures We genotyped 206,928 variants and imputed 17,642,824 variants in 1,076 youth (mean age 15.0 ±2.48 years) with T2D from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) and SEARCH for Diabetes in Youth (SEARCH) studies as part of the Progress in Diabetes Genetics in Youth (ProDiGY) consortium. We performed association testing for triglyceride, low-density lipoprotein (LDL-c) and high-density lipoprotein (HDL-c) concentrations adjusted for the genetic relationship matrix within each sub-study followed by meta-analyses for each trait. Results We identified a novel association between a deletion on chromosome 3 (3:67817380_AT/A_Deletion:RP11-81N13.1) and triglyceride levels at genome-wide level of significance (P=2.3×10 -8) with each risk allele increasing triglycerides by 20%. We also identified a genome-wide significant signal at rs247617 (P=5.1×10 -9) between HERFUD1 and CETP associated with HDL-c, with carriers of one copy of the risk allele having twice higher HDL-c. Conclusions Our genetic analyses of lipid traits in youth with T2D have identified one novel and one previously known locus. Additional studies are needed to further characterize the genetic architecture of dyslipidemia in youth with T2D.

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
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