T2D-GENES Multi-Ethnic Exome Sequencing Study: Ashkenazi

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 Malmö-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 Ashkenazi study contributed 506 cases and 352 controls to T2D-GENES Project 1. ]]>
Ashkenazi Jewish origin, defined as having all four grandparents born in Northern or Eastern Europe; subjects with known or suspected Sephardic Jewish or non-Jewish ancestry were excluded. T2D defined according to the World Health Organization criteria (fasting glucose >140 mg/dl on two or more occasions or random glucose >200mg/dl). To avoid late-onset T1D, patients who became insulin-dependent within 2 years of diagnosis were excluded; anti-GAD or anti-islet cell antibody titers were not routinely measured. T2D cases were selected from two separate DNA collections: Genome-wide, affected-sibling-pair linkage study (Permutt et al. Diabetes 2001). Families in which both parents were known to have diabetes were excluded. One affected individual selected from each family and, wherever possible, sibling with youngest age of diagnosis selected. Study to determine genetic risk for diabetic complications (Blech et al. PLoS One 2011). Patients ascertained by the Israel Diabetes Research Group between 2002 and 2004 from 15 diabetes clinics throughout Israel. Primary selection criteria: (1) known T1D or T2D for more than 10 years, (2) 4 grandparents being either Ashkenazi or Sephardic-North African Jewish. For this study, only T2D patients with all 4 grandparents of Ashkenazi Jewish origin and age of diagnosis between 35 and 60 were selected. Controls were determined according to the following criteria: Fasting blood glucose <7 mmol/l. No personal history of diabetes. No anti-diabetic medications. Patients who became insulin-dependent within 2 years of diagnosis were excluded.]]>
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: 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. 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. 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 http://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 http://www.einstein.yu.edu/centers/aging/longevity-genes-project/ Metabolic Syndrome in Men Study Markku Laakso http://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 http://www.lolipopstudy.org/ Singapore Indian Eye Study Wong Tien Yin http://www.seri.com.sg/key-programmes/singapore-epidemiology-of-eye-diseases-seed/ ]]>