Methods in Neuroepidemiology

Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis: The GENEVA Study
Rationale, Study Design and Demographic Characteristics
Silke Schmidt^{a, b}, Kelli D. Allen^{b, c}, Valerie T. Loiacono^{a, b}, Barbara Norman^{b, c}, Catherine L. Stanwyck^{a, b}, Kristina M. Nord^{a, b}, Christina D. Williams^{a, b}, Edward J. Kasarskis^e, Freya Kamel^d, Valerie McGuire^f, Lorene M. Nelson^f, Eugene Z. Oddone^{b, c}, VA ALS Registry Group

^aCenter for Human Genetics and
^bDepartment of Medicine, Duke University Medical Center, and
^cEpidemiology Research and Information Center, Durham VAMC, Durham, N.C.,
^dEpidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, N.C.,
^eLexington VAMC and University of Kentucky Medical Center, Lexington, Ky., and
^fStanford University School of Medicine, Stanford, Calif., USA

Address of Corresponding Author

Neuroepidemiology 2008;30:191-204 (DOI: 10.1159/000126911)

  Key Words

• Amyotrophic lateral sclerosis, case-control study
• GENEVA study recruitment methods
• Gene-environment interaction

  Abstract

Recent reports of a potentially increased risk of amyotrophic lateral sclerosis (ALS) for veterans deployed to the 1990-1991 Persian Gulf War prompted the Department of Veterans Affairs to establish a National Registry of Veterans with ALS, charged with the goal of enrolling all US veterans with a neurologist-confirmed diagnosis of ALS. The Genes and Environmental Exposures in Veterans with ALS study (GENEVA) is a case-control study presently enrolling cases from the Department of Veterans Affairs registry and a representative sample of veteran controls to evaluate the joint contributions of genetic susceptibility and environmental exposures to the risk of sporadic ALS. The GENEVA study design, recruitment strategies, methods of collecting DNA samples and environmental risk factor information are described here, along with a summary of demographic characteristics of the participants (537 cases, 292 controls) enrolled to date.

Copyright © 2008 S. Karger AG, Basel

  References

1.

Yoshida S, Mulder DW, Kurland LT, Chu CP, Okazaki H: Follow-up study on amyotrophic lateral sclerosis in Rochester, Minn., 1925 through 1984. Neuroepidemiology 1986;5:61-70.

2.

McGuire V, Longstreth WT Jr, Koepsell TD, Van Belle G: Incidence of amyotrophic lateral sclerosis in three counties in western Washington State. Neurology 1996;47:571-573.

3.

Traynor BJ, Codd MB, Corr B, Forde C, Frost E, Hardiman O: Incidence and prevalence of ALS in Ireland, 1995-1997: a population-based study. Neurology 1999;52:504-509.

4.

McGuire V, Nelson LM: Epidemiology of ALS; in Mitsumoto H, Przedborski S, Gordon P (eds): Amyotrophic Lateral Sclerosis. New York, Taylor & Francis, 2006, pp 17-21.

5.

Cronin S, Hardiman O, Traynor BJ: Ethnic variation in the incidence of ALS: a systematic review. Neurology 2007;68:1002-1007.

6.

Kunst CB: Complex genetics of amyotrophic lateral sclerosis. Am J Hum Genet 2004;75:933-947.

7.

Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O'Regan JP, Deng HX, Rahmani Z, Krizus A, McKenna-Yasek D, Cayabyab A, Gaston SM, Berger R, Tanzi RE, Halperin JJ, Herzfeldt B, Van den Bergh R, Hung WY, Bird T, Deng G, Mulder DW, Smyth C, Laing NG, Soriano E, Pericak-Vance MA, Haines J, Rouleau GA, Gusella J, Horvitz HR, Brown RH Jr: Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993;362:59-62.

8.

Chio A, Brignolio F, Meineri P, Schiffer D: Phenotypic and genotypic heterogeneity of dominantly inherited amyotrophic lateral sclerosis. Acta Neurol Scand 1987;75:277-282.

9.

Bruijn LI, Miller TM, Cleveland DW: Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu Rev Neurosci 2004;27:723-749.

10.

Mitchell J: Amyotrophic lateral sclerosis: toxins and environment. Amyotroph Lateral Scler Other Motor Neuron Disord 2000;1:235-250.

11.

Schmidt S, Vance JM: Genetic causes and predisposition; in Mitsumoto H, Przedborski S, Gordon P (eds): Amyotrophic Lateral Sclerosis. New York, Taylor & Francis, 2006, pp 449-485.

12.

Lambrechts D, Storkebaum E, Morimoto M, Del-Favero J, Desmet F, Marklund SL, Wyns S, Thijs V, Andersson J, van Marion I, Al-Chalabi A, Bornes S, Musson R, Hansen V, Beckman L, Adolfsson R, Pall HS, Prats H, Vermeire S, Rutgeerts P, Katayama S, Awata T, Leigh N, Lang-Lazdunski L, Dewerchin M, Shaw C, Moons L, Vlietinck R, Morrison KE, Robberecht W, Van Broeckhoven C, Collen D, Andersen PM, Carmeliet P: VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death. Nat Genet 2003;34:383-394.

13.

Terry PD, Kamel F, Umbach DM, Lehman TA, Hu H, Sandler DP, Taylor JA: VEGF promoter haplotype and amyotrophic lateral sclerosis (ALS). J Neurogenet 2004;18:429-434.

14.

Fernandez-Santiago R, Sharma M, Mueller JC, Gohlke H, Illig T, Anneser J, Munch C, Ludolph A, Kamm C, Gasser T: Possible gender-dependent association of vascular endothelial growth factor (VEGF) gene and ALS. Neurology 2006;66:1929-1931.

15.

Greenway MJ, Alexander MD, Ennis S, Traynor BJ, Corr B, Frost E, Green A, Hardiman O: A novel candidate region for ALS on chromosome 14q11.2. Neurology 2004;63:1936-1938.

16.

Greenway MJ, Andersen PM, Russ C, Ennis S, Cashman S, Donaghy C, Patterson V, Swingler R, Kieran D, Prehn J, Morrison KE, Green A, Acharya KR, Brown RH Jr, Hardiman O: ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis. Nat Genet 2006;38:411-413.

17.

Hayward C, Colville S, Swingler RJ, Brock DJH: Molecular genetic analysis of the APEX nuclease gene in amyotrophic lateral sclerosis (ALS). Neurology 1999;52:1899-1901.

18.

Goodall EF, Greenway MJ, van Marion I, Carroll CB, Hardiman O, Morrison KE: Association of the H63D polymorphism in the hemochromatosis gene with sporadic ALS. Neurology 2005;65:934-937.

19.

Sutedja NA, Sinke RJ, Van Vught PW, van der Linden MW, Wokke JH, Van Duijn CM, Njajou OT, Van der Schouw YT, Veldink JH, Van den Berg LH: The association between H63D mutations in HFE and amyotrophic lateral sclerosis in a Dutch population. Arch Neurol 2007;64:63-67.

20.

Veldink JH, Kalmijn S, Van der Hout AH, Lemmink HH, Groeneveld GJ, Lummen C, Scheffer H, Wokke JH, Van den Berg LH: SMN genotypes producing less SMN protein increase susceptibility to and severity of sporadic ALS. Neurology 2005;65:820-825.

21.

Corcia P, Camu W, Halimi JM, Vourc'h P, Antar C, Vedrine S, Giraudeau B, de Toffol B, Andres CR: SMN1 gene, but not SMN2, is a risk factor for sporadic ALS. Neurology 2006;67:1147-1150.

22.

Saeed M, Siddique N, Hung WY, Usacheva E, Liu E, Sufit RL, Heller SL, Haines JL, Pericak-Vance M, Siddique T: Paraoxonase cluster polymorphisms are associated with sporadic ALS. Neurology 2006;67:771-776.

23.

Slowik A, Tomik B, Wolkow PP, Partyka D, Turaj W, Malecki MT, Pera J, Dziedzic T, Szczudlik A, Figlewicz DA: Paraoxonase gene polymorphisms and sporadic ALS. Neurology 2006;67:766-770.

24.

Morahan JM, Yu B, Trent RJ, Pamphlett RA: Gene-environment study of the paraoxonase 1 gene and pesticides in amyotrophic lateral sclerosis. Neurotoxicology 2007;28:532-540.

25.

Cronin S, Greenway MJ, Prehn JH, Hardiman O: Paraoxonase promoter and intronic variants modify risk of sporadic amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2007;78:984-986.

26.

Furlong CE, Li WF, Brophy VH, Jarvik GP, Richter RJ, Shih DM, Lusis AJ, Costa LG: The PON1 gene and detoxication. Neurotoxicology 2000;21:581-587.

27.

Haley RW, Billecke S, La Du BN: Association of low PON1 type Q (type A) arylesterase activity with neurologic symptom complexes in Gulf War veterans. Toxicol Appl Pharmacol 1999;157:227-233.

28.

Al-Chalabi A, Enayat ZE, Bakker MC, Sham PC, Ball DM, Shaw CE, Lloyd CM, et al: Association of apolipoprotein E 4 allele with bulbar-onset motor neuron disease. Lancet 1996;347:159-160.

29.

Moulard B, Sefiani A, Laamri A, Malafosse A, Camu W: Apolipoprotein E genotyping in sporadic amyotrophic lateral sclerosis: evidence for a major influence on the clinical presentation and prognosis. J Neurol Sci 1996;139(suppl):34-37.

30.

Smith RG, Haverkamp LJ, Case S, Appel V, Appel SH: Apolipoprotein E 4 in bulbar-onset motor neuron disease. Lancet 1996;348:334-335.

31.

Li YJ, Pericak-Vance MA, Haines JL, Siddique N, McKenna-Yasek D, Hung WY, Sapp P, Allen CI, Chen W, Hosler B, Saunders AM, Dellefave LM, Brown RH Jr, Siddique T: Apolipoprotein E is associated with age at onset of amyotrophic lateral sclerosis. Neurogenetics 2004;5:209-213.

32.

Schymick JC, Scholz SW, Fung HC, Britton A, Arepalli S, Gibbs JR, Lombardo F, Matarin M, Kasperaviciute D, Hernandez DG, Crews C, Bruijn L, Rothstein J, Mora G, Restagno G, Chio A, Singleton A, Hardy J, Traynor BJ: 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.

33.

Dunckley T, Huentelman MJ, Craig DW, Pearson JV, Szelinger S, Joshipura K, Halperin RF, Stamper C, Jensen KR, Letizia D, Hesterlee SE, Pestronk A, Levine T, Bertorini T, Graves MC, Mozaffar T, Jackson CE, Bosch P, McVey A, Dick A, Barohn R, Lomen-Hoerth C, Rosenfeld J, O'Connor DT, Zhang K, Crook R, Ryberg H, Hutton M, Katz J, Simpson EP, Mitsumoto H, Bowser R, Miller RG, Appel SH, Stephan DA: Whole-genome analysis of sporadic amyotrophic lateral sclerosis. N Engl J Med 2007;357:775-788.

34.

van Es MA, Van Vught PW, Blauw HM, Franke L, Saris CG, Andersen PM, Van Den Bosch L, de Jong SW, van't Slot R, Birve A, Lemmens R, de Jong V, Baas F, Schelhaas HJ, Sleegers K, Van Broeckhoven C, Wokke JH, Wijmenga C, Robberecht W, Veldink JH, Ophoff RA, Van den Berg LH: ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Lancet Neurol 2007;6:869-877.

35.

Cronin S, Berger S, Ding J, Schymick JC, Washecka N, Hernandez DG, Greenway MJ, Bradley DG, Traynor BJ, Hardiman O: A genome-wide association study of sporadic ALS in a homogenous Irish population. Hum Mol Genet 2008;17:768-774.

36.

Deapen DM, Henderson BE: A case-control study of amyotrophic lateral sclerosis. Am J Epidemiol 1986;123:790-799.

37.

Savettieri G, Salemi G, Arcara A, Cassata M, Castiglione MG, Fierro BA: Case-control study of amyotrophic lateral sclerosis. Neuroepidemiology 1991;10:242-245.

38.

McGuire V, Longstreth WT Jr, Nelson LM, Koepsell TD, Checkoway H, Morgan MS, Van Belle G: Occupational exposures and amyotrophic lateral sclerosis: a population-based case-control study. Am J Epidemiol 1997;145:1076-1088.

39.

Campbell AM, Williams ER, Barltrop D: Motor neurone disease and exposure to lead. J Neurol Neurosurg Psychiatry 1970;33:877-885.

40.

Armon C, Kurland LT, Daube JR, O'Brien PC: Epidemiologic correlates of sporadic amyotrophic lateral sclerosis. Neurology 1991;41:1077-1084.

41.

Chancellor AM, Slattery JM, Fraser H, Warlow CP: Risk factors for motor neuron disease: a case-control study based on patients from the Scottish Motor Neuron Disease Register. J Neurol Neurosurg Psychiatry 1993;56:1200-1206.

42.

Kamel F, Umbach DM, Munsat TL, Shefner JM, Hu H, Sandler DP: Lead exposure and amyotrophic lateral sclerosis. Epidemiology 2002;13:311-319.

43.

Felmus MT, Patten BM, Swanke L: Antecedent events in amyotrophic lateral sclerosis. Neurology 1976;26:167-172.

44.

Pierce-Ruhland R, Patten BM: Repeat study of antecedent events in motor neuron disease. Ann Clin Res 1981;13:102-107.

45.

Gresham LS, Molgaard CA, Golbeck AL, Smith R: Amyotrophic lateral sclerosis and occupational heavy metal exposure: a case-control study. Neuroepidemiology 1986;5:29-38.

46.

Gunnarsson LG, Bodin L, Söderfeldt B, Axelson O: A case-control study of motor neurone disease: its relation to heritability, and occupational exposures, particularly to solvents. Br J Ind Med 1992;49:791-798.

47.

Kamel F, Umbach DM, Munsat TL, Shefner JM, Sandler DP: Association of cigarette smoking with amyotrophic lateral sclerosis. Neuroepidemiology 1999;18:194-202.

48.

Nelson LM, McGuire V, Longstreth WT Jr, Matkin C: Population-based case-control study of amyotrophic lateral sclerosis in western Washington State. I. Cigarette smoking and alcohol consumption. Am J Epidemiol 2000;151:156-163.

49.

Weisskopf MG, McCullough ML, Calle EE, Thun MJ, Cudkowicz M, Ascherio A: Prospective study of cigarette smoking and amyotrophic lateral sclerosis. Am J Epidemiol 2004;160:26-33.

50.

Longstreth WT, McGuire V, Koepsell TD, Wang Y, Van Belle G: Risk of amyotrophic lateral sclerosis and history of physical activity: a population-based case-control study. Arch Neurol 1998;55:201-206.

51.

Chio A, Benzi G, Dossena M, Mutani R, Mora G: Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players. Brain 2005;128:472-476.

52.

Belli S, Vanacore N: Proportionate mortality of Italian soccer players: is amyotrophic lateral sclerosis an occupational disease? Eur J Epidemiol 2005;20:237-242.

53.

Kondo K, Tsubaki T: Case-control studies of motor neuron disease: association with mechanical injuries. Arch Neurol 1981;38:220-226.

54.

Chen H, Richard M, Sandler DP, Umbach DM, Kamel F: Head injury and amyotrophic lateral sclerosis. Am J Epidemiol 2007;166:810-816.

55.

Kurtzke JF, Beebe GW: Epidemiology of amyotrophic lateral sclerosis: 1. A case-control comparison based on ALS deaths. Neurology 1980;30:453-462.

56.

Gallagher JP, Sanders M: Trauma and amyotrophic lateral sclerosis: a report of 78 patients. Acta Neurol Scand 1987;75:145-150.

57.

Gresham LS, Molgaard CA, Golbeck AL, Smith R: Amyotrophic lateral sclerosis and history of skeletal fracture: a case-control study. Neurology 1987;37:717-719.

58.

Granieri E, Carreras M, Tola R, Paolino E, Tralli G, Eleopra R, Serra G: Motor neuron disease in the province of Ferrara, Italy, in 1964-1982. Neurology 1988;38:1604-1608.

59.

Williams DB, Annegers JS, Kokman E, O'Brien PC, Kurland LT: Brain injury in neurologic sequalae: a cohort study of dementia, parkinsonism, and amyotrophic lateral sclerosis. Neurology 1991;41:1554-1557.

60.

Chio A, Meineri P, Tribolo A, Schiffer D: Risk factors in motor neuron disease: a case-control study. Neuroepidemiology 1991;10:174-184.

61.

Kamel F, Umbach DM, Lehman TA, Park LP, Munsat TL, Shefner JM, Sandler DP, Hu H, Taylor JA: Amyotrophic lateral sclerosis, lead, and genetic susceptibility: polymorphisms in the delta-aminolevulinic acid dehydratase and vitamin d receptor genes. Environ Health Perspect 2003;111:1335-1339.

62.

Smith TC, Gray GC, Knoke JD: Is systemic lupus erythematosus, amyotrophic lateral sclerosis, or fibromyalgia associated with Persian Gulf War service? An examination of department of defense hospitalization data. Am J Epidemiol 2000;151:1053-1059.

63.

Haley RW: Excess incidence of ALS in young Gulf War veterans. Neurology 2003;61:750-756.

64.

Horner RD, Kamins KG, Feussner JR, Grambow SC, Hoff-Lindquist J, Harati Y, Mitsumoto H, Pascuzzi R, Spencer PS, Tim R, Howard D, Smith TC, Ryan MA, Coffman CJ, Kasarskis EJ: Occurrence of amyotrophic lateral sclerosis among Gulf War veterans. Neurology 2003;61:742-749.

65.

Weisskopf MG, O'Reilly EJ, McCullough ML, Calle EE, Thun MJ, Cudkowicz M, Ascherio A: Prospective study of military service and mortality from ALS. Neurology 2005;64:32-37.

66.

Institute of Medicine Committee on the Review of the Scientific Literature on Amyotrophic Lateral Sclerosis in Veterans: Amyotrophic lateral sclerosis in veterans: review of the scientific literature. National Academies Press, 2006. http://www.nap.edu/catalog/ 11757.html.

67.

Kasarkis EJ, Dominic K, Oddone EZ: The National Registry of Veterans with Amyotrophic Lateral Sclerosis: Department of Veterans Affairs Cooperative Studies Program (CSP) #500a. Amyotroph Lateral Scler Other Motor Neuron Disord 2004;5(suppl 1):129-132.

68.

DiMartino L, Allen KD, Kasarskis E, Lindquist JH, Coffman CJ, Oddone EZ: Characteristics associated with participation in DNA banking: The National Registry of Veterans with ALS. Contemp Clin Trials 2007;28:572-582.

69.

Brooks BR: El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis'' workshop contributors. J Neurol Sci 1994;124 (suppl):96-107.

70.

Brooks BR, Miller RG, Swash M, Munsat T: El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000;1:293-299.

71.

Kubal JD, Webber S, Cowper DC, Waight S, Hynes DM: A primer on major US mortality databases used in health services research. VIReC Insights 2000;5:1-4. http://www.virec. research.va.gov/HistoricalDocuments/ VirecInsights/Insights-v01n5.pdf

72.

Boyle CA, Decoufle P: National sources of vital status information: extent of coverage and possible selectivity in reporting. Am J Epidemiol 1990;131:160-168.

73.

Page WF, Braun MM, Caporaso NE: Ascertainment of mortality in the US veteran population: World War II veteran twins. Mil Med 1995;160:351-355.

74.

Fisher SG, Weber L, Goldberg J, Davis F: mortality ascertainment in the veteran population: alternatives to the National Death Index. Am J Epidemiol 1995;141:242-250.

75.

Larson RJ, Welch HG: Risk for increased utilization and adverse health outcomes among men served by the Veterans Health Administration. Mil Med 2007;172:690-696.

76.

Dillman DA: Mail and Internet Surveys: The Tailored Design Method, ed 2. New York, Wiley & Sons, 2000.

77.

Gauderman WJ: Sample size requirements for matched case-control studies of gene-environment interaction. Stat Med 2002;21:35-50.

78.

Doebbeling BN, Jones MF, Hall DB, Clarke WR, Woolson RF, Torner JC, Burmeister LF, Snyders-Crumley T, Barrett DH, Falter KH, Merchant JA, Nusser S, Anderson D, Schwartz DA: Methodologic issues in a population-based health survey of Gulf War veterans. J Clin Epidemiol 2002;55:477-487.

79.

Ryan MA, Smith TC, Smith B, Amoroso P, Boyko EJ, Gray GC, Gackstetter GD, Riddle JR, Wells TS, Gumbs G, Corbeil TE, Hooper TI: Millennium Cohort: enrollment begins a 21-year contribution to understanding the impact of military service. J Clin Epidemiol 2007;60:181-191.

80.

Weathers FW, Litz BT, Herman DS, Huska JA, Keane TM: The PTSD Checklist Military Version (PCL-M). Boston, National Center for PTSD, 1991. http://www.pdhealth.mil/guidelines/appendix4.asp.

81.

Weathers FW, Litz BT, Herman DS, Huska JA, Keane TM: The PTSD checklist: reliability, validity, and diagnostic utility (abstract). Annu Meet Int Soc Trauma Stress Studies, San Antonio, Tex., 1993.

82.

Lang AJ, Laffaye C, Satz LE, Dresselhaus TR, Stein MB: Sensitivity and specificity of the PTSD checklist in detecting PTSD in female veterans in primary care. J Trauma Stress 2003;16:257-264.

83.

Brewin CR: Systematic review of screening instruments for adults at risk of PTSD. J Trauma Stress 2005;18:53-62.

84.

Chio A: ISIS Survey: an international study on the diagnostic process and its implications in amyotrophic lateral sclerosis. J Neurol 1999;246(suppl 3):III1-III5.

85.

Stewart WF, Stewart, PA: Occupational case-control studies. I. Collecting information on work histories and work-related exposures. Am J Ind Med 1994;26:297-312.

86.

Stewart PA, Stewart WF: Occupational case-control studies. II. Recommendations for exposure assessment. Am J Ind Med 1994;26:313-326.

87.

Piegorsch WW, Weinberg CR, Taylor JA: Non-hierarchical logistic models and case-only designs for assessing susceptibility in population-based case-control studies. Stat Med 1994;13:153-162.

88.

Morton LM, Cahill J, Hartge P: Reporting participation in epidemiologic studies: a survey of practice. Am J Epidemiol 2006;163:197-203.

89.

Hartge P: Participation in population studies. Epidemiology 2006;17:252-254.

90.

Bhatti P, Sigurdson AJ, Wang SS, Chen J, Rothman N, Hartge P, Bergen AW, Landi MT: Genetic variation and willingness to participate in epidemiologic research: data from three studies. Cancer Epidemiol Biomarkers Prev 2005;14:2449-2453.

91.

Gatto NM, Campbell UB, Rundle AG, Ahsan H: Further development of the case-only design for assessing gene-environment interaction: evaluation of and adjustment for bias. Int J Epidemiol 2004;33:1014-1024.

92.

Sturmer T, Brenner H: Flexible matching strategies to increase power and efficiency to detect and estimate gene-environment interactions in case-control studies. Am J Epidemiol 2002;155:593-602.

93.

Coffman CJ, Horner RD, Grambow SC, Lindquist J: Estimating the occurrence of amyotrophic lateral sclerosis among Gulf War (1990-1991) veterans using capture-recapture methods. Neuroepidemiology 2005;24:141-150.

94.

Smith TC, Jacobson IG, Smith B, Hooper TI, Ryan MA, Team FT: The occupational role of women in military service: validation of occupation and prevalence of exposures in the Millennium Cohort Study. Int J Environ Health Res 2007;17:271-284.

  Author Contacts

Silke Schmidt, PhD
Center for Human Genetics, Department of Medicine
Duke University Medical Center, Box 3445
Durham, NC 27710 (USA)
Tel. +1 919 684 0624, Fax +1 919 684 0925, E-Mail silke.schmidt@duke.edu

  Article Information

Received: October 31, 2007
Accepted: January 31, 2008
Published online: April 18, 2008
Number of Print Pages : 14
Number of Figures : 3, Number of Tables : 3, Number of References : 94

  Publication Details

Neuroepidemiology

Vol. 30, No. 3, Year 2008 (Cover Date: May 2008)

Journal Editor: Feigin V.L. (Auckland)
ISSN: 0251-5350 (Print), eISSN: 1423-0208 (Online)

For additional information: http://www.karger.com/NED

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