Multiple sclerosis in US veterans of the Vietnam era and later military service: Race, sex, and geography

Department of Veterans Affairs Medical Center, Georgetown University Medical School, Washington, DC, USA.
Annals of Neurology (Impact Factor: 11.91). 01/2004; 55(1):65-71. DOI: 10.1002/ana.10788
Source: PubMed

ABSTRACT We identified 5345 cases of multiple sclerosis (MS) among US veterans who first entered military service between 1960 and 1994, and who were "service-connected" for MS by the Department of Veterans Affairs (VA). Two controls per case were matched on age, date of service entry, and branch of service. Available for service and VA files were demographic and military data for 4951 cases and 9378 controls. Versus white men, relative risk of MS was significantly higher for all women, at 2.99 for whites, 2.86 for blacks, and 3.51 for those of other races. This was a significant increase from our prior series of veterans of World War II and the Korean Conflict, where white women had a relative risk of 1.79. Risk for black men was higher now (0.67 vs 0.44), while other men remained low (0.30 vs 0.22). Residence at service entry in the northern tier of states had a relative risk of 2.02 versus the southern tier, which was significantly less than the 2.64 for the earlier series. Residence by individual state at birth and service entry for white men further supported this decreasing geographic differential. Such marked changes in geography, sex, and race in such a short interval strongly imply a primary environmental factor in the cause or precipitation of this disease.


Available from: John F Kurtzke, Mar 09, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The possibility of a link between active smoking and incident multiple sclerosis (MS) has been raised. However, possible links between incidence of MS and passive smoking, particularly in children, have not been analysed. We conducted a population-based, case-control study. The cases were patients with incident MS occurring between 1994 and 2003, before the age of 16 years, in France. Each case was matched for age, sex and geographic origin with 12 controls, randomly selected from the French general population. Information about the smoking history of the parents of the cases and controls was collected with a standardized questionnaire. Conditional logistic regression was used to estimate the rate ratio (RR) of MS associated with parental smoking at home. The 129 cases of MS were matched with 1038 controls. Information about parental smoking was obtained for all these cases and controls. Exposure to parental smoking was noted in 62.0% of cases and 45.1% of controls. The adjusted RR of a first episode of MS associated with exposure to parental smoking at home was 2.12 (95% confidence interval: 1.43-3.15). Stratification for age showed that this increase in risk was significantly associated with the longer duration of exposure in older cases (over 10 years of age at the time of the index episode)-RR 2.49 (1.53-4.08)-than in younger cases. Children exposed to parent smoking have a higher MS risk. The duration of exposure also affects the level of risk.
    Brain 11/2007; 130(Pt 10):2589-95. DOI:10.1093/brain/awm198 · 10.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Admixture mapping (also known as "mapping by admixture linkage disequilibrium," or MALD) has been proposed as an efficient approach to localizing disease-causing variants that differ in frequency (because of either drift or selection) between two historically separated populations. Near a disease gene, patient populations descended from the recent mixing of two or more ethnic groups should have an increased probability of inheriting the alleles derived from the ethnic group that carries more disease-susceptibility alleles. The central attraction of admixture mapping is that, since gene flow has occurred recently in modern populations (e.g., in African and Hispanic Americans in the past 20 generations), it is expected that admixture-generated linkage disequilibrium should extend for many centimorgans. High-resolution marker sets are now becoming available to test this approach, but progress will require (a). computational methods to infer ancestral origin at each point in the genome and (b). empirical characterization of the general properties of linkage disequilibrium due to admixture. Here we describe statistical methods to estimate the ancestral origin of a locus on the basis of the composite genotypes of linked markers, and we show that this approach accurately estimates states of ancestral origin along the genome. We apply this approach to show that strong admixture linkage disequilibrium extends, on average, for 17 cM in African Americans. Finally, we present power calculations under varying models of disease risk, sample size, and proportions of ancestry. Studying approximately 2500 markers in approximately 2500 patients should provide power to detect many regions contributing to common disease. A particularly important result is that the power of an admixture mapping study to detect a locus will be nearly the same for a wide range of mixture scenarios: the mixture proportion should be 10%-90% from both ancestral populations.
    The American Journal of Human Genetics 06/2004; 74(5):979-1000. DOI:10.1086/420871 · 10.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Admixture mapping is a whole genome association strategy that takes advantage of population history-or genetic ancestry-to map genes for complex diseases. However, because it uses racial/ethnic groupings to examine differential disease risk, admixture mapping raises ethical and social concerns. While there has been much theoretical commentary regarding the ethical and social implications of population-based genetic research, empirical data from stakeholders most closely involved with these studies is limited. One of the first admixture mapping studies carried out was a scan for Multiple Sclerosis (MS) risk factors in an African-American population. Applying qualitative research methods, we used this example to explore developing views, experiences and perceptions of the ethical and social implications of admixture mapping and other population-based research-their value, risks and benefits, and the future prospects of the field. Additionally, we sought to understand how social and ethical risks might be mitigated, and the benefits of this research optimized. We draw on in-depth, one-on-one interviews with leading population geneticists, genome scientists, bioethicists, and African-Americans with MS. Here we present our findings from this unique group of key informants and stakeholders.
    12/2010; 4(1-4):23-34. DOI:10.1007/s11568-010-9145-y