Slim Initiative in Genomic Medicine for the Americas (SIGMA): Diabetes in Mexico Study (DMS)

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: Type 2 Diabetes (SIGMA T2D)
• 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 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: https://esp.gs.washington.edu/drupal/dbGaP_Releases.

The Diabetes in Mexico Study (DMS) study contributed 1,522 cases and 1,546 controls to the 52k T2D exome sequencing study.

• Study Weblinks:
  • SIGMAT2D
• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
  • Cohort
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 3296
• Subject Sample Telemetry Report (SSTR)

• BioProject
• Sequence Read Archive
• BioSample
• MeSH

Cases were ascertained according to the following criteria:

• Age =18 years
• previous T2D diagnosis or fasting glucose levels above 125 mg/dL
• excluded individuals with fasting glycemia between 100-125 mg/dL

Controls were determined according to the following criteria:

• Age =45 years
• fasting glucose levels below 100 mg/dL

Slim Initiative in Genomic Medicine for the Americas: Type 2 Diabetes (SIGMA T2D) is an international research consortium funded by the Carlos Slim Foundation that investigates genetic risk factors of type 2 diabetes within Mexican and Latin American populations and translates those finding to improved methods of treatment and prevention. The organizations involved include: Broad Institute, Massachusetts General Hospital, University of Southern California, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Instituto Nacional de Medicina Genómica, Instituto Nacional de Salud Pública, and the Carlos Slim Foundation.

The SIGMA T2D collaboration effort consists of two projects:

1. SIGMAv1 focused on generating a GWAS data set of 8,214 Hispanic T2D case and control samples. We then performed whole exome sequencing on 3,756 of those samples.
2. SIGMAv2 generated whole exome sequencing and supplemental GWAS array data for an additional 9,041 Hispanic T2D case and control samples.

This submission reflects the activities that occurred in SIGMA T2D v1 & v2. Each of the studies involved in SIGMA T2D consortia 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 52k T2D exome sequencing study. For more information on these studies, please see table 2.

• Primary Phenotype: Diabetes Mellitus, Type 2

• Principal Investigators
  • Jose Florez. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA, and Massachusetts General Hospital, Boston, MA, USA.
  • Michael Boehnke. University of Michigan, Ann Arbor, MI, USA.
  • Mark McCarthy. Wellcome Trust Centre for Human Genetics, Oxford, UK.
  • David Altshuler. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Lorena Orozco. Instituto Nacional de Medicina Genómica, Tlalpan, Mexico.
• Institute
  • The Broad Institute of Harvard and MIT. The Broad Institute of Harvard and MIT, Cambridge, MA, USA.
• Funding Source
  • Slim Initiative in Genomic Medicine for the Americas (SIGMA). Carlos Slim Foundation.