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Study Description

This sub-study phs001098 T2D GENES Exome Seq contains genotype derived from sequence data and selected phenotype of subjects available from the phs001098 study. Summary level phenotypes for the NHLBI JHS Cohort study participants can be viewed at the top-level study page phs000286 JHS Cohort. Individual level phenotype data and molecular data for all JHS Cohort top-level study and sub-study are available by requesting Authorized Access to the NHLBI JHS Cohort phs000286 study.

T2D-GENES (Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples) is a NIDDK-funded international research consortium which seeks to identify genetic variants for type 2 diabetes (T2D) through multiethnic sequencing studies. T2D-GENES Project 1 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 14 cohorts that are listed in Table 1. The strategy was to perform deep exome sequencing of 12,940 individuals, 6,504 with T2D and 6,436 controls, divided among five ancestry groups: Europeans, East Asians, South Asians, American Hispanics, and African Americans. Sequencing was performed at the Broad Institute using the Agilent v2 capture reagent on Illumina HiSeq machines. Please note that while we summarize the full sample list in publications and below, the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) study does not have a sub study, as it is not consented to be deposited in dbGAP.

Table 1. T2D-GENES Whole Exome Sequencing Studies

Ancestry Study Countries of Origin # Cases # Controls
African American Jackson Heart Study US 502 527
African American Wake Forest School of Medicine Study US 518 532
East Asian Korea Association Research Project Korea 526 561
East Asian Singapore Diabetes Cohort Study; Singapore Prospective Study Program Singapore (Chinese) 486 592
European Ashkenazi US, Israel 506 352
European Metabolic Syndrome in Men Study (METSIM) Finland 484 498
European Finland-United States Investigation of NIDDM Genetics (FUSION) Study Finland 472 476
European Kooperative Gesundheitsforschung in der Region Augsburg (KORA) Germany 97 90
European UK Type 2 Diabetes Genetics Consortium (UKT2D) UK 322 320
European Malmo-Botnia Study Finland, Sweden 478 443
Hispanic 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 US 272 219
Hispanic Starr County, Texas US 749 704
South Asian London Life Sciences Population Study (LOLIPOP) UK (Indian Asian) 530 538
South Asian Singapore Indian Eye Study Singapore (Indian Asian) 563 585

The Jackson Heart Study contributed 502 cases and 527 controls to T2D-GENES Project 1.

Authorized Access
Publicly Available Data (Public ftp)
Study Inclusion/Exclusion Criteria

Cases were ascertained according to the following criteria:

  • Genomic DNA from blood and genome-wide genotypes available (minimum 25 ug DNA remaining)
  • Non-related individuals based on family IDs
  • ADA 2004 definition of T2D diagnosed either of two exams
  • Samples with age of onset <16 years and treated only with insulin were excluded

Controls were determined by the following criteria:

  • No T2D by ADA 2004 definition, fasting plasma glucose <100 mg/dl, and HbA1c <6% at each of two exams
  • Controls were matched to cases in a two-stage approach:
  1. Strong matches (greedy algorithm): age > 50, sex match, BMI within 1 unit, and age within 5 years (N=457 matched pairs)
  2. Closest available matches: sex match and BMI > 25; for females, BMI within 5 units and age within 20 years; for males, BMI within 8 units and age within 25 years (N=117 matched pairs)

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Exome Sequencing Agilent SureSelect Human All Exon v2 - 44Mb N/A N/A
Study History

T2D-GENES (Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples) is a NIDDK-funded international research consortium which seeks to identify genetic variants for type 2 diabetes (T2D) through multiethnic sequencing studies. The organizations involved in the NIDDK U01 include: Broad Institute, University of Michigan, University of Oxford, NIDDK/NIH, University of Chicago, Texas Biomedical Research Institute, Massachusetts General Hospital, University of Texas Health Science Center, University of North Carolina, Blood Systems Research Institute, and University of Mississippi Medical Center.

The T2D-GENES collaboration effort consists of 3 projects:

  1. Project 1 seeks 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.
  2. Project 2 is focused on the role of rare and private variants on T2D risk, and is based on deep whole genome sequencing of -600 members of 20 Mexican American pedigrees. Pedigree members are extensively phenotyped and have been genotyped with Illumina GWAS chips.
  3. Project 3 seeks to determine whether multiethnic GWAS meta-analysis might assist in fine-mapping T2D association signals by strengthening evidence for T2D association and narrowing the association interval. Project 3 has focused initially on analysis of five T2D loci chosen as likely candidates for success of this approach.

This submission reflects the activities that occurred in T2D-GENES Project 1. Each of the studies involved in T2D-GENES Project1 are part of larger cohorts. While each participating cohort has specific cohort information and history, that information is not summarized here as we have specifically selected these samples for type 2 diabetes research as part of the T2D-GENES study. For more information on these studies, please see table 2.

Table 2. Studies contributing samples to T2D-GENES Project 1

Study Name PI(s) Study URL (if available)
Jackson Heart Study Candidate Gene Association Resource Jim Wilson www.jacksonheartstudy.org
Wake Forest Study Donald Bowden
Korea Association Research Project (KARE) and Korean National Institute of Health (KNIH) Jong-Young Lee and Yoon Shin Cho
Singapore Diabetes Cohort Study and Singapore Prospective Study Program Daniel Ng Peng Keat and Tai E. Shyong http://www.nus-cme.org.sg/about.html
Longevity Genes in Founder Populations (Ashkenazi) Nir Barzilai,Gil Atzmon www.einstein.yu.edu/centers/aging/longevity-genes-project/
Metabolic Syndrome in Men Study Markku Laakso www.nationalbiobanks.fi/index.php/studies2/10-metsim
San Antonio Mexican American Family Studies, Texas Ravindranath Duggirala
Starr County, Texas Craig Hanis
London Life Sciences Population (LOLIPOP) Jaspal Kooner www.lolipopstudy.org/
Singapore Indian Eye Study Wong Tien Yin www.seri.com.sg/key-programmes/singapore-epidemiology-of-eye-diseases-seed/
Selected publications
Diseases/Traits Related to Study (MeSH terms)
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