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Mexico City Diabetes Study SIGMA Exome Sequencing Project

ABSTRACT: Mexico City Diabetes Study SIGMA Exome Sequencing Project

PROVIDER: PRJNA389148 | ENA |

REPOSITORIES: ENA

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Project description:The ~52,000 sample Type 2 Diabetes Exome Sequencing project is a collaboration of six consortia with various funding mechanisms that have joined together to investigate genetic variants for type 2 diabetes (T2D) using the largest T2D case/control sample set compiled to date. This includes samples from: <ul> <li>Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES)</li> <li>Genetics of Type 2 Diabetes (GoT2D)</li> <li>Exome Sequencing Project (ESP)</li> <li>Slim Initiative in Genomic Medicine for the Americas: Type 2 Diabetes (SIGMA T2D)</li> <li>Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCAMP)</li> <li>Progress in Diabetes Genetics in Youth (ProDIGY)</li> </ul> This data generated from the SIGMA Diabetes in Mexico Study (DMS) was part of the Slim Initiative in Genomic Medicine for the Americas: Type 2 Diabetes (SIGMA T2D), which is an international research consortium funded by the Carlos Slim Foundation that seeks to identify the genetic risk factors for type 2 diabetes (T2D) in Mexico and Latin America and translate those findings into improved treatment and prevention of diabetes. The SIGMA T2D project has sequenced and genotyped more than 13,000 samples from Mexican and Mexican Americans. The individuals were obtained from over 20 cohorts across the 6 consortia that are listed in Table 1. The strategy was to perform deep exome sequencing of individuals, 24,991 with T2D and 24,953 controls, divided among five ancestry groups: Europeans, East Asians, South Asians, American Hispanics, and African Americans. The T2D-GENES, ProDIGY and SIGMA studies, sequencing was performed at the Broad Institute using the Agilent v2 capture reagent or Illumina Rapid Capture on Illumina HiSeq machines. Please note that while we summarize the full sample list in publications and below, two of the cohorts below are not in dbGAP, due to the samples not being consented for deposition. This includes the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) study and Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCamp) study. The Exome Sequencing Project (ESP) was deposited in dbGAP as part of their initial study and the phs numbers for that project can be found here: <a href="https://esp.gs.washington.edu/drupal/dbGaP_Releases">https://esp.gs.washington.edu/drupal/dbGaP_Releases</a>. <table style="width:100%" border="1"> <caption>Table 1. 52,000 sample T2D Case/Control Whole Exome Sequencing Studies</caption> <tr> <th>Ancestry</th> <th>Consortia</th> <th>Study</th> <th>Countries of Origin</th> <th># Cases</th> <th># Controls</th> </tr> <tr> <td>African American</td> <td>T2D-GENES Project 1</td> <td>Jackson Heart Study</td> <td>US</td> <td>500</td> <td>526</td> </tr> <tr> <td>African American</td> <td>T2D-GENES Project 1</td> <td>Wake Forest School of Medicine Study</td> <td>US</td> <td>518</td> <td>530</td> </tr> <tr> <td>African American</td> <td>ESP</td> <td>Exome Sequencing Project (ESP)</td> <td>US</td> <td>467</td> <td>1374</td> </tr> <tr> <td>African American</td> <td>T2D-GENES Follow up study</td> <td>BioMe Biobank Program (BioMe)</td> <td>US</td> <td>1297</td> <td>1256</td> </tr> <tr> <td>East Asian</td> <td>T2D-GENES Project 1</td> <td>Korea Association Research Project</td> <td>Korea</td> <td>526</td> <td>561</td> </tr> <tr> <td>East Asian</td> <td>T2D-GENES Project 1& Follow up Study</td> <td>Singapore Diabetes Cohort Study; Singapore Prospective Study Program</td> <td>Singapore (Chinese)</td> <td>1486</td> <td>1568</td> </tr> <tr> <td>East Asian</td> <td>T2D-GENES Follow up study</td> <td>Korea SNUH</td> <td>South Korea</td> <td>450</td> <td>475</td> </tr> <tr> <td>East Asian</td> <td>T2D-GENES Follow up study</td> <td>Research Studies in Hong Kong (Hong Kong)</td> <td>Hong Kong</td> <td>493</td> <td>485</td> </tr> <tr> <td>European</td> <td>T2D-GENES Project 1</td> <td>Ashkenazi</td> <td>US, Israel</td> <td>506</td> <td>355</td> </tr> <tr> <td>European</td> <td>T2D-GENES Project 1</td> <td>Metabolic Syndrome in Men Study (METSIM)</td> <td>Finland</td> <td>484</td> <td>498</td> </tr> <tr> <td>European</td> <td>GoT2D</td> <td>Finland-United States Investigation of NIDDM Genetics (FUSION) Study</td> <td>Finland</td> <td>472</td> <td>476</td> </tr> <tr> <td>European</td> <td>GoT2D</td> <td>Kooperative Gesundheitsforschung in der Region Augsburg (KORA)</td> <td>Germany</td> <td>97</td> <td>90</td> </tr> <tr> <td>European</td> <td>GoT2D</td> <td>UK Type 2 Diabetes Genetics Consortium (UKT2D)</td> <td>UK</td> <td>322</td> <td>320</td> </tr> <tr> <td>European</td> <td>GoT2D</td> <td>Malmo-Botnia Study</td> <td>Finland, Sweden</td> <td>478</td> <td>443</td> </tr> <tr> <td>European</td> <td>LuCamp</td> <td>Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCamp)</td> <td>Denmark</td> <td>997</td> <td>997</td> </tr> <tr> <td>European</td> <td>ESP</td> <td>Exome Sequencing Project (ESP)</td> <td>US</td> <td>390</td> <td>2843</td> </tr> <tr> <td>European</td> <td>T2D-GENES Follow up study</td> <td>Genetics of Diabetes and Audit Research Tayside Study (GoDARTS)</td> <td>Scotland, UK</td> <td>960</td> <td>966</td> </tr> <tr> <td>European</td> <td>T2D-GENES Follow up study</td> <td>Framingham Heart Study (FHS)</td> <td>US</td> <td>396</td> <td>596</td> </tr> <tr> <td>Hispanic</td> <td>T2D-GENES Project 1</td> <td>San Antonio Family Heart Study, San Antonio Family Diabetes/ Gallbladder Study, Veterans Administration Genetic Epidemiology Study, and the Investigation of Nephropathy and Diabetes Study Family Component</td> <td>US</td> <td>272</td> <td>218</td> </tr> <tr> <td>Hispanic</td> <td>T2D-GENES Project 1 & SIGMAv2</td> <td>Starr County, Texas</td> <td>US</td> <td>1762</td> <td>1738</td> </tr> <tr> <td>Hispanic</td> <td>SIGMAv1</td> <td>Mexico City Diabetes Study</td> <td>Mexico</td> <td>281</td> <td>549</td> </tr> <tr> <td>Hispanic</td> <td>SIGMAv1 & v2</td> <td>Multiethnic Cohort (MEC)</td> <td>US</td> <td>1476</td> <td>1443</td> </tr> <tr> <td>Hispanic</td> <td>SIGMAv1 & v2</td> <td>UNAM/INCMNSZ Diabetes Study (UIDS)</td> <td>Mexico</td> <td>1998</td> <td>1977</td> </tr> <tr> <td>Hispanic</td> <td>SIGMAv1 & v2</td> <td>Diabetes in Mexico Study (DMS)</td> <td>Mexico</td> <td>1522</td> <td>1546</td> </tr> <tr> <td>Multi ethnic</td> <td>ProDIGY</td> <td>Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY)</td> <td>US</td> <td>3097</td> <td>0</td> </tr> <tr> <td>Multi ethnic</td> <td>ProDIGY</td> <td>SEARCH for Diabetes in Youth (SEARCH)</td> <td>US</td> <td>553</td> <td>0</td> </tr> <tr> <td>South Asian</td> <td>T2D-GENES Project 1</td> <td>London Life Sciences Population Study (LOLIPOP)</td> <td>UK (Indian Asian)</td> <td>531</td> <td>538</td> </tr> <tr> <td>South Asian</td> <td>T2D-GENES Project 1 & Follow up study</td> <td>Singapore Indian Eye Study</td> <td>Singapore (Indian Asian)</td> <td>1640</td> <td>1478</td> </tr> <tr> <td>South Asian</td> <td>T2D-GENES Follow up study</td> <td>Pakistan Genomic Resource (PGR)</td> <td>Pakistan</td> <td>914</td> <td>932</td> </tr> </table> The Diabetes in Mexico Study (DMS) study contributed 1,522 cases and 1,546 controls to the 52k T2D exome sequencing study.

Project description:BACKGROUND:Most large, prospective studies of the effects of diabetes on mortality have focused on high-income countries where patients have access to reasonably good medical care and can receive treatments to establish and maintain good glycemic control. In those countries, diabetes less than doubles the rate of death from any cause. Few large, prospective studies have been conducted in middle-income countries where obesity and diabetes have become common and glycemic control may be poor. METHODS:From 1998 through 2004, we recruited approximately 50,000 men and 100,000 women 35 years of age or older into a prospective study in Mexico City, Mexico. We recorded the presence or absence of previously diagnosed diabetes, obtained and stored blood samples, and tracked 12-year disease-specific deaths through January 1, 2014. We accepted diabetes as the underlying cause of death only for deaths that were due to acute diabetic crises. We estimated rate ratios for death among participants who had diabetes at recruitment versus those who did not have diabetes at recruitment; data from participants who had chronic diseases other than diabetes were excluded from the main analysis. RESULTS:At the time of recruitment, obesity was common and the prevalence of diabetes rose steeply with age (3% at 35 to 39 years of age and >20% by 60 years of age). Participants who had diabetes had poor glycemic control (mean [±SD] glycated hemoglobin level, 9.0±2.4%), and the rates of use of other vasoprotective medications were low (e.g., 30% of participants with diabetes were receiving antihypertensive medication at recruitment and 1% were receiving lipid-lowering medication). Previously diagnosed diabetes was associated with rate ratios for death from any cause of 5.4 (95% confidence interval [CI], 5.0 to 6.0) at 35 to 59 years of age, 3.1 (95% CI, 2.9 to 3.3) at 60 to 74 years of age, and 1.9 (95% CI, 1.8 to 2.1) at 75 to 84 years of age. Between 35 and 74 years of age, the excess mortality associated with previously diagnosed diabetes accounted for one third of all deaths; the largest absolute excess risks of death were from renal disease (rate ratio, 20.1; 95% CI, 17.2 to 23.4), cardiac disease (rate ratio, 3.7; 95% CI, 3.2 to 4.2), infection (rate ratio, 4.7; 95% CI, 4.0 to 5.5), acute diabetic crises (8% of all deaths among participants who had previously diagnosed diabetes), and other vascular disease (mainly stroke). Little association was observed between diabetes and mortality from cirrhosis, cancer, or chronic obstructive pulmonary disease. CONCLUSIONS:In this study in Mexico, a middle-income country with high levels of obesity, diabetes was common, glycemic control was poor, and diabetes was associated with a far worse prognosis than that seen in high-income countries; it accounted for at least one third of all deaths between 35 and 74 years of age. (Funded by the Wellcome Trust and others.).

Project description:The ~52,000 sample Type 2 Diabetes Exome Sequencing project is a collaboration of six consortia with various funding mechanisms that have joined together to investigate genetic variants for type 2 diabetes (T2D) using the largest T2D case/control sample set compiled to date. This includes samples from: <ul> <li>Type 2 Diabetes Genetic Exploration by Next-generation sequencing in Multi-Ethnic Samples (T2D-GENES)</li> <li>Genetics of Type 2 Diabetes (GoT2D)</li> <li>Exome Sequencing Project (ESP)</li> <li>Slim Initiative in Genomic Medicine for the Americas (SIGMA)</li> <li>Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCAMP)</li> <li>Progress in Diabetes Genetics in Youth (ProDIGY)</li> </ul> This data generated from the Pakistan Genomic Resource (PGR) cohort was part of the T2-GENES (Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples) consortium, which is a NIDDK-funded international research consortium that seeks to identify genetic variants for type 2 diabetes (T2D) through multiethnic sequencing studies. The T2D-GENES Project is a multi-ethnic sequencing study designed to assess whether less common variants play a role in T2D risk and to assess similarities and differences in the distribution of T2D risk variants across ancestry groups. The individuals were obtained from over 20 cohorts across the 6 consortia that are listed in Table 1. The strategy was to perform deep exome sequencing of individuals, 24,991 with T2D and 24,953 controls, divided among five ancestry groups: Europeans, East Asians, South Asians, American Hispanics, and African Americans. The T2D-GENES, ProDIGY and SIGMA studies, sequencing was performed at the Broad Institute using the Agilent v2 capture reagent or Illumina Rapid Capture on Illumina HiSeq machines. Please note that while we summarize the full sample list in publications and below, two of the cohorts below are not in dbGAP, due to the samples not being consented for deposition. This includes the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) study and Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCamp) study. The Exome Sequencing Project (ESP) was deposited in dbGAP as part of their initial study and the phs numbers for that project can be found here: https://esp.gs.washington.edu/drupal/dbGaP_Releases. Table 1. 52,000 sample T2D Case/Control Whole Exome Sequencing Studies <table border="1"> <tr> <th>Ancestry</th> <th>Consortia</th> <th>Study</th> <th>Countries of Origin</th> <th># Cases</th> <th># Controls</th> </tr> <tr> <td>African American</td> <td>T2D-GENES Project 1</td> <td>Jackson Heart Study</td> <td>US</td> <td>502</td> <td>527</td> </tr> <tr> <td>African American</td> <td>T2D-GENES Project 1</td> <td>Wake Forest School of Medicine Study</td> <td>US</td> <td>518</td> <td>532</td> </tr> <tr> <td>African American</td> <td>ESP</td> <td>Exome Sequencing Project (ESP)</td> <td>US</td> <td>467</td> <td>1374</td> </tr> <tr> <td>African American</td> <td>T2D-GENES Follow-Up Study</td> <td>BioMe Biobank Program (BioMe)</td> <td>US</td> <td>1297</td> <td>1256</td> </tr> <tr> <td>East Asian</td> <td>T2D-GENES Project 1</td> <td>Korea Association Research Project</td> <td>Korea</td> <td>526</td> <td>561</td> </tr> <tr> <td>East Asian</td> <td>T2D-GENES Project 1 and Follow-Up Study</td> <td>Singapore Diabetes Cohort Study; Singapore Prospective Study Program</td> <td>Singapore (Chinese)</td> <td>1486</td> <td>1568</td> </tr> <tr> <td>East Asian</td> <td>T2D-GENES Follow-Up Study</td> <td>Korea SNUH</td> <td>South Korea</td> <td>450</td> <td>475</td> </tr> <tr> <td>East Asian</td> <td>T2D-GENES Follow-Up Study</td> <td>Research Studies in Hong Kong (Hong Kong)</td> <td>Hong Kong</td> <td>493</td> <td>485</td> </tr> <tr> <td>European</td> <td>T2D-GENES Project 1</td> <td>Ashkenazi</td> <td>US, Israel</td> <td>506</td> <td>355</td> </tr> <tr> <td>European</td> <td>T2D-GENES Project 1</td> <td>Metabolic Syndrome in Men Study (METSIM)</td> <td>Finland</td> <td>484</td> <td>498</td> </tr> <tr> <td>European</td> <td>GoT2D</td> <td>Finland-United States Investigation of NIDDM Genetics (FUSION) Study</td> <td>Finland</td> <td>472</td> <td>476</td> </tr> <tr> <td>European</td> <td>GoT2D</td> <td>Kooperative Gesundheitsforschung in der Region Augsburg (KORA)</td> <td>Germany</td> <td>97</td> <td>90</td> </tr> <tr> <td>European</td> <td>GoT2D</td> <td>UK Type 2 Diabetes Genetics Consortium (UKT2D)</td> <td>UK</td> <td>322</td> <td>320</td> </tr> <tr> <td>European</td> <td>GoT2D</td> <td>Malmö-Botnia Study</td> <td>Finland, Sweden</td> <td>478</td> <td>443</td> </tr> <tr> <td>European</td> <td>LuCamp</td> <td>Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCamp)</td> <td>Denmark</td> <td>997</td> <td>997</td> </tr> <tr> <td>European</td> <td>ESP</td> <td>Exome Sequencing Project (ESP)</td> <td>US</td> <td>390</td> <td>2843</td> </tr> <tr> <td>European</td> <td>T2D-GENES Follow-Up Study</td> <td>Genetics of Diabetes and Audit Research Tayside Study (GoDARTS)</td> <td>Scotland, UK</td> <td>960</td> <td>966</td> </tr> <tr> <td>European</td> <td>T2D-GENES Follow-Up Study</td> <td>Framingham Heart Study (FHS)</td> <td>US</td> <td>396</td> <td>596</td> </tr> <tr> <td>Hispanic</td> <td>T2D-GENES Project 1</td> <td>San Antonio Family Heart Study, San Antonio Family Diabetes/ Gallbladder Study, Veterans Administration Genetic Epidemiology Study, and the Investigation of Nephropathy and Diabetes Study Family Component</td> <td>US</td> <td>272</td> <td>218</td> </tr> <tr> <td>Hispanic</td> <td>T2D-GENES Project 1 and SIGMA v2</td> <td>Starr County, Texas</td> <td>US</td> <td>1762</td> <td>1738</td> </tr> <tr> <td>Hispanic</td> <td>SIGMA v1</td> <td>Mexico City Diabetes Study</td> <td>Mexico</td> <td>281</td> <td>549</td> </tr> <tr> <td>Hispanic</td> <td>SIGMA v1 and SIGMA v2</td> <td>Multiethnic Cohort (MEC)</td> <td>US</td> <td>1476</td> <td>1443</td> </tr> <tr> <td>Hispanic</td> <td>SIGMA v1 and SIGMA v2</td> <td>UNAM/INCMNSZ Diabetes Study (UIDS)</td> <td>Mexico</td> <td>1998</td> <td>1977</td> </tr> <tr> <td>Hispanic</td> <td>SIGMA v1 and SIGMA v2</td> <td>Diabetes in Mexico Study (DMS)</td> <td>Mexico</td> <td>1522</td> <td>1546</td> </tr> <tr> <td>Multiethnic</td> <td>ProDIGY</td> <td>Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY)</td> <td>US</td> <td>3097</td> <td>0</td> </tr> <tr> <td>Multiethnic</td> <td>ProDIGY</td> <td>SEARCH for Diabetes in Youth (SEARCH)</td> <td>US</td> <td>553</td> <td>0</td> </tr> <tr> <td>South Asian</td> <td>T2D-GENES Project 1</td> <td>London Life Sciences Population Study (LOLIPOP)</td> <td>UK (Indian Asian)</td> <td>531</td> <td>538</td> </tr> <tr> <td>South Asian</td> <td>T2D-GENES Project 1 and Follow-Up Study</td> <td>Singapore Indian Eye Study</td> <td>Singapore (Indian Asian)</td> <td>1640</td> <td>1478</td> </tr> <tr> <td>South Asian</td> <td>T2D-GENES Follow-Up Study</td> <td>Pakistan Genomic Resource (PGR)</td> <td>Pakistan</td> <td>903</td> <td>930</td> </tr> </table> The PGR study contributed 903 cases and 930 controls to T2D-GENES Follow-Up Study.

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Mexico City Diabetes Study SIGMA Exome Sequencing Project

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