Whole Genome Scan for Type 2 Diabetes in a Scandinavian Cohort

David Altshuler (principal investigator)
Leif Groop (principal investigator)
Thomas Hughes (principal investigator)

Project Overview

Type 2 diabetes shows strong heritability, yet to date only a small fraction of familial clustering has been explained by genes identified through linkage analysis and candidate-gene association studies. To the extent that common variants significantly influence risk of type 2 diabetes and related metabolic traits, they can potentially be identified by genome-wide association studies that are unbiased with regard to prior hypotheses about disease mechanisms or gene annotations. Such studies are now practical enabled by clinical investigation of patients with type 2 diabetes, data from the Human Genome Project, SNP map and International HapMap Projects, high-throughput genotyping, and appropriate statistical genetic and epidemiological analyses.

We performed a whole genome association study in 3,000 Scandinavian individuals using the Affymetrix Human Mapping 500K GeneChip®, to search for genetic variants that influence risk of type 2 diabetes. As a secondary aim we are analyzing the same data to identify associations between variants and traits related to glucose, obesity, lipids and blood pressure. We are following up these patients to understand the role genetic variation plays in complications and the trajectory of the disease. In order to design, collect, analyze, and interpret the whole genome associations study we have assembled Focus teams that span the collaborating groups.

  • Phenotype and Follow-up: led by clinical and genetic investigators in Sweden and Finland, as well as from Boston, and is responsible for identifying and clinically characterizing a well-powered and well-matched sample for study of type 2 diabetes and clinical traits of interest. (Team leaders: Richa Saxena, Valeri Lyssenko; Chair: Leif Groop)
  • Genotyping: responsible for quality control and inventory of DNA samples, fingerprint genotyping for sample tracking, genome-wide genotyping in support of the whole genome scan, and follow-up genotyping to further explore putative associations. (Team Leader: Candace Guiducci; Chair; Noël Burtt and Stacey Gabriel (Director, Genetic Analysis Platform))
  • Analysis: responsible for quality control of genotype data, and the population genetic, statistical and epidemiological analysis of association to diabetes and other related metabolic traits. (Team leaders: Paul de Bakker, Ben Voight; Chair: Mark Daly)
  • Pathway: developing knowledge-based and association-driven analyses to evaluate epistasis and pathway enrichment. (Team Leader: Darrell Ricke; Chair: Joel Hirschhorn)
  • Project Management: responsible for project tracking and management (Team Leader: Noël Burtt; Chair: David Altshuler)

Study Design and Methods


A Note about early access to the data:
We are making the genome scan results publicly available prior to publication so that researchers interested in the genetics of T2D can use the results of the scan to prioritize follow-up of any regions of interest. We plan to publish the results of the scan, with much more detailed discussion, in due time.