The Finland-United States Investigation of NIDDM Genetics (FUSION) Study

The Finland-United States Investigation of NIDDM Genetics (FUSION) study is a long-term effort to identify genetic variants that predispose to type 2 diabetes (T2D) or that impact the variability of T2D-related quantitative traits. The initial effort involved linkage analysis of affected-sibling-pair (ASP) families based on over 5,000 individuals living in Finland, and association fine mapping based on these family members and additional T2D cases and controls. We completed a genome-wide association scan on 1161 T2D cases and 1174 normal glucose tolerant (NGT) controls. Individual-level data is available for the 919 T2D cases and 787 NGT controls who reconsented to the use of their data or are deceased (phs000100). In addition, we selected these 919 T2D cases and a matched set of 919 NGT controls (774 overlapping with GWAS) for targeted sequencing of 78 genes associated with glucose, insulin, and/or lipids. 400 of these T2D cases were also chosen for whole-exome sequencing (phs000702).

• Study Weblinks:
  • FUSION (Finland-United States Investigation of NIDDM Genetics) Study
• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
• Total number of consented subjects: 1850
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• Sequence Read Archive
• BioSample
• MeSH
• PMC

Cases: T2D cases were selected from FUSION ASP families, each reporting at least one T2D sibling, and from Finrisk 2002, a Finnish population-based risk factor survey. T2D was defined by WHO 1999 criteria of fasting plasma glucose >= 7.0 mmol/l or 2-h plasma glucose >= 11.1 mmol/l, by report of diabetes medication use, or based on medical record review. FUSION cases with known or probable type 1 diabetes among their first degree relatives were excluded.

Controls: NGT controls for GWAS were selected from FUSION, including subjects from Vantaa, Finland, who were NGT at ages 65 and 70 years, and spouses of FUSION subjects, and from Finrisk 2002. Additional NGT controls for sequencing were selected from D2D 2004, Finrisk 1987, Health 2000, and the Savitaipale Diabetes Study. NGT was defined by WHO 1999 criteria of fasting glucose < 6.1 mmol/l and 2-h glucose < 7.8 mmol/l. Controls were frequency-matched to the cases as described in the sub-study descriptions.

• Oct 1994 - Apr 1996: FUSION 1 ASP family primary data collection
• Dec 1996 - Aug 1998: FUSION 2 ASP primary data collection and collection of additional FUSION 1 family members
• 2000: FUSION 1 linkage genome scan papers published
• 2004: FUSION 2 linkage genome scan paper published
• 2004 - 2006: Sampling of additional FUSION 1 and 2 family members and unrelated T2D cases and NGT controls
• 2006: Genome-wide association scan genotyping completed
• 2007: T2D genome-wide association scan paper published in Science
• 2014: Re-sequencing study paper published in PLoS Genetics

• Primary Phenotype: Diabetes Mellitus, Type 2

• Principal Investigators
  • Michael Boehnke. University of Michigan, Ann Arbor, MI, USA.
  • Francis Collins. National Institutes of Health, Bethesda, MD, USA.
  • Richard Bergman. Cedars-Sinai Medical Center, West Hollywood, CA, USA.
  • Jaakko Tuomilehto. National Public Health Institute, Helsinki, Finland.
  • Karen Mohlke. University of North Carolina, Chapel Hill, NC, USA.
• Co-Investigators
  • Laura Scott. University of Michigan, Ann Arbor, MI, USA.
  • Lori Bonnycastle. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Timo Valle. National Public Health Institute, Helsinki, Finland.
  • Heather Stringham. University of Michigan, Ann Arbor, MI, USA.
  • Anne Jackson. University of Michigan, Ann Arbor, MI, USA.
  • Tom Buchanan. University of Southern California, Los Angeles, CA, USA.
  • Richard Watanabe. University of Southern California, Los Angeles, CA, USA.
  • Peter Chines. NHGRI, NIH, Bethesda, MD, USA.
  • Mike Erdos. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Cristen Willer. University of Michigan, Ann Arbor, MI, USA.
  • Gonçalo Abecasis. University of Michigan, Ann Arbor, MI, USA.
• Funding Source
  • DK062370. National Institutes of Health, Bethesda, MD, USA.