Genome-Wide Association Study of Amyotrophic Lateral Sclerosis in Finland

The genetic etiology of amyotrophic lateral sclerosis (ALS) is not well understood. Finland has one of the highest incidence of ALS in the world, making it an ideal population for study. To identify genetic risk factors for this fatal neurodegenerative disease, we undertook a genome-wide association study of 405 Finnish patients diagnosed with ALS and 497 Finnish controls. Two loci that exceeded the Bonferroni threshold for genome-wide significance were identified. One was located on chromosome 21q22, corresponding to the known autosomal recessive D90A allele of the SOD1 gene. The other was detected on the short arm of chromosome 9, which had been previously identified in linkage studies of families with ALS. Together, these two loci account for most of the increased incidence of ALS observed in this population.

• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 896
• Subject Sample Telemetry Report (SSTR)

Inclusion/exclusion criteria for cases

All DNA samples were obtained from patients who:

1. had been diagnosed with ALS according to the El Escorial diagnostic criteria published by the World Federation of Neurology;
2. were White and non-Hispanics (by self-report);
3. were Finnish (by self-report);
4. had signed informed consent.

The current data release is in conjunction with our Lancet Neurology paper (Laaksovirta et al., 2010). This release of data includes 896 samples for which participants provided consent to make their data publicly available. Six samples were removed for quality control reasons.

• Primary Phenotype: Amyotrophic Lateral Sclerosis

• Principal Investigators
  • Bryan J. Traynor. Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Pentti J. Tienari. Department of Neurology, Helsinki University Central Hospital and Molecular Neurology Programme, Biomedicum, University of Helsinki, Helsinki, Finland.
• Co-Investigators
  • Hannu Laaksovirta. Department of Neurology, Helsinki University Central Hospital and Molecular Neurology Programme, Biomedicum, University of Helsinki, Helsinki, Finland.
  • Terhi Peuralinna. Department of Neurology, Helsinki University Central Hospital and Molecular Neurology Programme, Biomedicum, University of Helsinki, Helsinki, Finland.
  • Jennifer C. Schymick. Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Sonja W. Scholz. Molecular Genetics Unit, Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD, USA.
  • Shiao-Lin Lai. Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Liisa Myllykangas. Department of Pathology, Haartman Institute, University of Helsinki and Folkhälsan Research Center, Helsinki, Finland.
  • Raimo Sulkava. Section of Geriatrics, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
  • Lilja Jansson. Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Dena Hernandez. Molecular Genetics Unit, Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD, USA.
  • J. Raphael Gibbs. Computational Biology Core, Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD, USA.
  • Michael Nalls. Molecular Genetics Unit, Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD, USA.
  • David Heckerman. Microsoft Research, Los Angeles, CA, USA.
• Funding
  • Project Z01 AG000949-02. Intramural Research Program of the National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Microsoft Research.
  • The ALS Association, USA.
  • The Helsinki University Central Hospital.
  • The Finnish Academy.
  • The Finnish Medical Society Duodecim.
  • Kuopio University.