Type 2 Diabetes Genetic Exploration by Next-Generation Sequencing in Multi-Ethnic Samples (T2D-GENES) Project 1: KARE

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

The Korea Association Research Project (KARE) studies contributed 526 cases and 561 controls to T2D-GENES Project 1.

• Study Weblinks:
  • T2D-GENES
• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 1087
• Subject Sample Telemetry Report (SSTR)

• PubMed

• Past history of T2D.
• Use of T2D medication.
• Fasting plasma glucose >/=7 mmol/l or plasma glucose >/=11.1 mmol/l 2 hours after ingestion of 75gm oral glucose load.
• Age of disease onset >/=40 years.
• Participants with early onset and family history prioritized.

• No past history of diabetes.
• No anti-diabetic medication.
• Fasting plasma glucose <5.6 mmol/l and plasma glucose 2 hours after ingestion of 75g oral glucose load <7.8 mmol/l at both baseline and follow up timepoints.
• Older subjects with normal glucose prioritized.

Samples with age of diagnosis <40 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:

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

• Primary Phenotype: Diabetes Mellitus, Type 2

• Principal Investigators
  • David Altshuler. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Michael Boehnke. University of Michigan, Ann Arbor, MI.
  • Mark McCarthy. Wellcome Trust Centre for Human Genetics, Oxford, UK.
  • Jose Florez. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA; Massachusetts General Hospital, Boston, MA, USA.
• Sequencing Institute
  • The Broad Institute of Harvard and MIT. Cambridge, MA, USA.
• Funding Sources
  • U01DK085526 (Multiethnic Study of Type 2 Diabetes Genes). National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
  • U54HG003067 (Large Scale Sequencing and Analysis of Genomes). National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.