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Original article
Genome-wide scan linkage analysis for Parkinson’s disease: the European genetic study of Parkinson’s disease
  1. M Martinez1,
  2. A Brice2,
  3. J R Vaughan3,
  4. A Zimprich4,
  5. M M B Breteler5,
  6. G Meco6,
  7. A Filla7,
  8. M J Farrer8,
  9. C Bétard9,
  10. J Hardy10,
  11. G De Michele7,
  12. V Bonifati6,
  13. B Oostra11,
  14. T Gasser4,
  15. N W Wood12,
  16. A Dürr2,
  17. the French Parkinson’s Disease Genetics Study Group, the European Consortium on Genetic Susceptibility in Parkinson’s Disease
  1. 1INSERM EMI00-06, Evry, France
  2. 2INSERM U289 and Département de Génétique, Cytogénétique et Embryologie, Hôpital La Pitité-Salpêtrière, Paris, France
  3. 3Department of Neurology Charing Cross Hospital, London, UK
  4. 4Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany
  5. 5Department of Epidemiology and Biostatistics, Erasmus University, Rotterdam, Netherlands
  6. 6Department of Neurological Sciences, La Sapienza University, Rome, Italy
  7. 7Department of Neurological Sciences, Federico II University, Naples, Italy
  8. 8Neurogenetics Laboratory, Mayo Clinic Jacksonville, Florida, USA
  9. 9Centre National de Génotypage, Evry, France
  10. 10Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, Maryland, USA
  11. 11Department of Clinical Genetics, Erasmus University, Rotterdam, Netherlands
  12. 12Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK
  1. Correspondence to:
 Dr Maria Martinez
 Unité de Recherche INSERM EMI00-06, Tour Evry 2, 523 Place des Terrasses de l’Agora, Evry cedex 91068, France; mariaevry.inserm.fr

Abstract

Objective: To undertake a full genome-wide screen for Parkinson’s disease susceptibility loci.

Methods: A genome-wide linkage study was undertaken in 227 affected sibling pairs from 199 pedigrees with Parkinson’s disease. The pedigree sample consisted of 188 pedigrees from five European countries, and 11 from the USA. Individuals were genotyped for 391 microsatellite markers at ∼10 cM intervals throughout the genome. Multipoint model-free affected sibling pair linkage analyses were carried out using the MLS (maximum LOD score) test.

Results: There were six chromosomal regions with maximum MLS peaks of 1 or greater (pointwise p<0.018). Four of these chromosomal regions appear to be newly identified regions, and the highest MLS values were obtained on chromosomes 11q (MLS = 1.60, at 91 cM, D11S4175) and 7p (MLS = 1.51, at 5 cM, D7S531). The remaining two MLS peaks, on 2p11–q12 and 5q23, are consistent with excess sharing in regions reported by other studies. The highest MLS peak was observed on chromosome 2p11–q12 (MLS = 2.04, between markers D2S2216 and D2S160), within a relatively short distance (∼17 cM) from the PARK3 region. Although a stronger support of linkage to this region was observed in the late age of onset subgroup of families, these differences were not significant. The peak on 5q23 (MLS = 1.05, at 130 cM, D5S471) coincides with the region identified by three other genome scans. All peak locations fell within a 10 cM distance.

Conclusions: These stratified linkage analyses suggest linkage heterogeneity within the sample across the 2p11–q12 and 5q23 regions, with these two regions contributing independently to Parkinson’s disease susceptibility.

  • ASP, affected sibling pair
  • IBD, identical by descent
  • LOD, logarithm of odds
  • MLS, maximum LOD score
  • UPDRS, unified Parkinson’s disease rating score
  • Parkinson’s disease
  • genome-wide linkage study

https://doi.org/10.1136/jmg.2004.022632

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    Footnotes

    • Conflicts of interest: none declared

    • The French Parkinson’s Disease Genetics Study Group: Y Agid, A-M Bonnet, M Borg, A Brice, E Broussolle, P Damier, A Destée, A Dürr, F Durif, J Feingold, G Fénelon, E Lohmann, M Martinez, C Penet, P Pollak, O Rascol, F Tison, C Tranchant, M Vérin, F Viallet, M Vidailhet, and J-M Warter

      The European Consortium on Genetic Susceptibility in Parkinson’s Disease: N W Wood and D Nicholl (UK); A Brice, A Dürr, M Martinez and Y Agid (France); T Gasser and B Müller-Myhsok (Germany); M Breteler, S Harhangi and B Oostra (Netherlands); V Bonifati, E Fabrizio, N Vanacore, G Meco, G De Michele, G Volpe and A Filla (Italy).