Type 2 Diabetes Genetic Exploration by Next Generation Sequencing in Multi-Ethnic Samples (T2D-GENES) Follow-up Study: Framingham Heart Study

This substudy phs001610 Framingham T2D-GENES contains next-generation sequencing in multi-ethnic samples. Summary level phenotypes for the Framingham Cohort study participants can be viewed at the top-level study page [phs000007](./study.cgi?study_id=phs000007) Framingham Cohort. Individual level phenotype data and molecular data for all Framingham top-level study and substudies are available by requesting Authorized Access to the Framingham Cohort study [phs000007](./study.cgi?study_id=phs000007).

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:
- Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) - Genetics of Type 2 Diabetes (GoT2D) - Exome Sequencing Project (ESP) - Slim Initiative in Genomic Medicine for the Americas (SIGMA) - Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCAMP) - Progress in Diabetes Genetics in Youth (ProDIGY)

This data generated from the Framingham Heart Study (FHS) cohort was part of the T2D-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](https://esp.gs.washington.edu/drupal/dbGaP_Releases).

Table 1. 52,000 sample T2D Case/Control Whole Exome Sequencing Studies
<td width="89"> **Ancestry** </td> <td width="114"> **Consortia** </td> <td width="203"> **Study** </td> <td width="82"> **Countries of Origin** </td> <td width="59"> **# Cases** </td> <td width="76"> **# Controls** </td>

**Consortia**

**Countries of Origin**

**# Controls**
<td width="89"> African American </td> <td width="114"> T2D-GENES Project 1 </td> <td width="203"> Jackson Heart Study </td> <td width="82"> US </td> <td width="59"> 500 </td> <td width="76"> 526 </td>

T2D-GENES Project 1

US

526
<td width="89"> African American </td> <td width="114"> T2D-GENES Project 1 </td> <td width="203"> Wake Forest School of Medicine Study </td> <td width="82"> US </td> <td width="59"> 518 </td> <td width="76"> 530 </td>

T2D-GENES Project 1

US

530
<td width="89"> African American </td> <td width="114"> ESP </td> <td width="203"> Exome Sequencing Project (ESP) </td> <td width="82"> US </td> <td width="59"> 467 </td> <td width="76"> 1374 </td>

ESP

US

1374
<td width="89"> African American </td> <td width="114"> T2D-GENES Follow up study </td> <td width="203"> BioMe Biobank Program (BioMe) </td> <td width="82"> US </td> <td width="59"> 1297 </td> <td width="76"> 1256 </td>

T2D-GENES Follow up study

US

1256
<td width="89"> East Asian </td> <td width="114"> T2D-GENES Project 1 </td> <td width="203"> Korea Association Research Project </td> <td width="82"> Korea </td> <td width="59"> 526 </td> <td width="76"> 561 </td>

T2D-GENES Project 1

Korea

561
<td width="89"> East Asian </td> <td width="114"> T2D-GENES Project 1&amp; Follow up Study </td> <td width="203"> Singapore Diabetes Cohort Study; Singapore Prospective Study Program </td> <td width="82"> Singapore (Chinese) </td> <td width="59"> 1486 </td> <td width="76"> 1568 </td>

T2D-GENES Project 1&amp; Follow up Study

Singapore (Chinese)

1568
<td width="89"> East Asian </td> <td width="114"> T2D-GENES Follow up study </td> <td width="203"> Korea SNUH </td> <td width="82"> South Korea </td> <td width="59"> 450 </td> <td width="76"> 475 </td>

T2D-GENES Follow up study

South Korea

475
<td width="89"> East Asian </td> <td width="114"> T2D-GENES Follow up study </td> <td width="203"> Research Studies in Hong Kong (Hong Kong) </td> <td width="82"> Hong Kong </td> <td width="59"> 493 </td> <td width="76"> 485 </td>

T2D-GENES Follow up study

Hong Kong

485
<td width="89"> European </td> <td width="114"> T2D-GENES Project 1 </td> <td width="203"> Ashkenazi </td> <td width="82"> US, Israel </td> <td width="59"> 506 </td> <td width="76"> 355 </td>

T2D-GENES Project 1

US, Israel

355
<td width="89"> European </td> <td width="114"> T2D-GENES Project 1 </td> <td width="203"> Metabolic Syndrome in Men Study (METSIM) </td> <td width="82"> Finland </td> <td width="59"> 484 </td> <td width="76"> 498 </td>

T2D-GENES Project 1

Finland

498
<td width="89"> European </td> <td width="114"> GoT2D </td> <td width="203"> Finland-United States Investigation of NIDDM Genetics (FUSION) Study </td> <td width="82"> Finland </td> <td width="59"> 472 </td> <td width="76"> 476 </td>

GoT2D

Finland

476
<td width="89"> European </td> <td width="114"> GoT2D </td> <td width="203"> Kooperative Gesundheitsforschung in der Region Augsburg (KORA) </td> <td width="82"> Germany </td> <td width="59"> 97 </td> <td width="76"> 90 </td>

GoT2D

Germany

90
<td width="89"> European </td> <td width="114"> GoT2D </td> <td width="203"> UK Type 2 Diabetes Genetics Consortium (UKT2D) </td> <td width="82"> UK </td> <td width="59"> 322 </td> <td width="76"> 320 </td>

GoT2D

UK

320
<td width="89"> European </td> <td width="114"> GoT2D </td> <td width="203"> Malmo-Botnia Study </td> <td width="82"> Finland, Sweden </td> <td width="59"> 478 </td> <td width="76"> 443 </td>

GoT2D

Finland, Sweden

443
<td width="89"> European </td> <td width="114"> LuCamp </td> <td width="203"> Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCamp) </td> <td width="82"> Denmark </td> <td width="59"> 997 </td> <td width="76"> 997 </td>

LuCamp

Denmark

997
<td width="89"> European </td> <td width="114"> ESP </td> <td width="203"> Exome Sequencing Project (ESP) </td> <td width="82"> US </td> <td width="59"> 390 </td> <td width="76"> 2843 </td>

ESP

US

2843
<td width="89"> European </td> <td width="114"> T2D-GENES Follow up study </td> <td width="203"> Genetics of Diabetes and Audit Research Tayside Study (GoDARTS) </td> <td width="82"> Scotland, UK </td> <td width="59"> 960 </td> <td width="76"> 966 </td>

T2D-GENES Follow up study

Scotland, UK

966
<td width="89"> European </td> <td width="114"> T2D-GENES Follow up study </td> <td width="203"> Framingham Heart Study (FHS) </td> <td width="82"> US </td> <td width="59"> 396 </td> <td width="76"> 596 </td>

T2D-GENES Follow up study

US

596
<td width="89"> Hispanic </td> <td width="114"> T2D-GENES Project 1 </td> <td width="203"> 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 width="82"> US </td> <td width="59"> 272 </td> <td width="76"> 218 </td>

T2D-GENES Project 1

US

218
<td width="89"> Hispanic </td> <td width="114"> T2D-GENES Project 1 &amp; SIGMAv2 </td> <td width="203"> Starr County, Texas </td> <td width="82"> US </td> <td width="59"> 1762 </td> <td width="76"> 1738 </td>

T2D-GENES Project 1 &amp; SIGMAv2

US

1738
<td width="89"> Hispanic </td> <td width="114"> SIGMAv1 </td> <td width="203"> Mexico City Diabetes Study </td> <td width="82"> Mexico </td> <td width="59"> 281 </td> <td width="76"> 549 </td>

SIGMAv1

Mexico

549
<td width="89"> Hispanic </td> <td width="114"> SIGMAv1 &amp; v2 </td> <td width="203"> Multiethnic Cohort (MEC) </td> <td width="82"> US </td> <td width="59"> 1476 </td> <td width="76"> 1443 </td>

SIGMAv1 &amp; v2

US

1443
<td width="89"> Hispanic </td> <td width="114"> SIGMAv1 &amp; v2 </td> <td width="203"> UNAM/INCMNSZ Diabetes Study (UIDS) </td> <td width="82"> Mexico </td> <td width="59"> 1998 </td> <td width="76"> 1977 </td>

SIGMAv1 &amp; v2

Mexico

1977
<td width="89"> Hispanic </td> <td width="114"> SIGMAv1 &amp; v2 </td> <td width="203"> Diabetes in Mexico Study (DMS) </td> <td width="82"> Mexico </td> <td width="59"> 1522 </td> <td width="76"> 1546 </td>

SIGMAv1 &amp; v2

Mexico

1546
<td width="89"> Multi ethnic </td> <td width="114"> ProDIGY </td> <td width="203"> Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) </td> <td width="82"> US </td> <td width="59"> 3097 </td> <td width="76"> 0 </td>

ProDIGY

US

0
<td width="89"> Multi ethnic </td> <td width="114"> ProDIGY </td> <td width="203"> SEARCH for Diabetes in Youth (SEARCH) </td> <td width="82"> US </td> <td width="59"> 553 </td> <td width="76"> 0 </td>

ProDIGY

US

0
<td width="89"> South Asian </td> <td width="114"> T2D-GENES Project 1 </td> <td width="203"> London Life Sciences Population Study (LOLIPOP) </td> <td width="82"> UK (Indian Asian) </td> <td width="59"> 531 </td> <td width="76"> 538 </td>

T2D-GENES Project 1

UK (Indian Asian)

538
<td width="89"> South Asian </td> <td width="114"> T2D-GENES Project 1 &amp; Follow up study </td> <td width="203"> Singapore Indian Eye Study </td> <td width="82"> Singapore (Indian Asian) </td> <td width="59"> 1640 </td> <td width="76"> 1478 </td>

T2D-GENES Project 1 &amp; Follow up study

Singapore (Indian Asian)

1478
<td width="89"> South Asian </td> <td width="114"> T2D-GENES Follow up study </td> <td width="203"> Pakistan Risk of Myocardial Infarction Study (PROMIS) </td> <td width="82"> Pakistan </td> <td width="59"> 914 </td> <td width="76"> 932 </td>

T2D-GENES Follow up study

Pakistan

932

The FHS study contributed 396 cases and 596 controls to T2D-GENES Follow up study.