1
Appendix e-1: Description of study populations
Country / Population / Cases / Controls% Male / % bulbar
onset / Age at onset / % Male / Age at recruitment
POL / 51% / 29% / 53.4 ± 13.1 / 46% / 57.2 ± 17.6
SWE / 58% / 36% / 61.8 ± 12.7 / 54% / 59.8 ± 14
NL / 60% / 32% / 60.4 ± 12.6 / 58% / 63.3 ± 9.4
BEL / 60% / 24% / 58.6 ± 12.6 / 53% / 53.4 ± 21.1
ITA / 54% / 27% / 60.5 ± 11.0 / 46% / 66.8 ± 14.9
UK / London / 61% / 30% / 56.8 ± 12.5 / 63% / 55.6 ± 12.2
WTCCC / - / - / - / 50% / 50 ± 0
US / 63% / 24% / 53.9 ± 12.9 / 52% / 61.1 ± 13.9
BEL: Belgium; ITA: Italy; NL: The Netherlands; POL: Poland; SWE: Sweden; UK: United Kingdom; US: United States; WTCCC: Wellcome Trust Case Control Consortium
Belgium: Individuals with sporadic ALS were unrelated and from self reported Flemishdescent. All patients were referred to the University Hospital Gasthuisberg in Leuven. Controls consisted of unrelated, healthy, Flemish controls.
The Netherlands: ALS patients were referred to the University Medical Centre Utrecht, the Academic Medical Centre Amsterdam, or the Radboud University Nijmegen Medical Centre. Controls consisted of unrelated, healthy volunteers who accompanied non-ALS patients to the UMC Utrecht neurology outpatient clinic and controls recruited from an ongoing, prospective population-based study on ALS in The Netherlands. All participants were of Dutch descent and were 55 years of age or oldere1, e2.
Italy:
Patients and controls of white ethnicity were recruited from different centers in Italy.
Poland:
Sporadic ALS patients who presented to the MND Clinic at the Jagiellonian University in Krakow from 2003 were included in this study. The control group included unrelated individuals taken from the population of southern Poland. Control subjects had no apparent neurological disease based on the findings of astructured questionnaire and neurological examination. Controls were matched to the patients with respect to the age (+/- 3 years) of the cases at disease onset and gender. Bothcases and the controls were of Caucasian origin and Polish descente2.
Sweden: Individuals with sporadic ALS were unrelated Swedish citizens who reported (northern)Swedish citizenship for at least three generations and were referred to the Umeå University ALS Clinic. The Swedish control samples were spouses of the patients or unrelated healthy controls matched for age and gendere2.
United States of America:
Cases and controls were from white, non-Hispanic ethnicity and collected from many different regions across the USAe3. ALS patients were also recruited from the Massachusetts General Hospitalin Boston or the Emory University Hospital in Atlanta. Control samples for this cohort were healthy volunteers from the Boston area or spouses of ALS patients and additionally healthy control samples were purchased from the Coriell Institute for Medical Researche4.
United Kingdom:
Sporadic ALS patients were referred to the department of Neurology at the Institute of Psychiatry in London. 237 control samples were collected from neurologically normal, unrelated individuals, either spouses of ALS patients, carers or blood donors from the same geographical regione4. UK controls additionally included 2,938 individuals typed as part of the Wellcome Trust Case Control Consortiume5.
e-References
e1.van Es MA, Van Vught PW, Blauw HM, et al. ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Lancet Neurol 2007;6:869-877.
e2.van Es MA, Veldink JH, Saris CG, et al. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis. Nat Genet 2009;41:1083-1087.
e3.Schymick JC, Scholz SW, Fung HC, et al. Genome-wide genotyping in amyotrophic lateral sclerosis and neurologically normal controls: first stage analysis and public release of data. Lancet Neurol 2007;6:322-328.
e4.Landers JE, Melki J, Meininger V, et al. Reduced expression of the Kinesin-Associated Protein 3 (KIFAP3) gene increases survival in sporadic amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 2009;106:9004-9009.
e5.Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007;447:661-678.