Background & Aims-The historical prevalence and long-term outcome of undiagnosed celiac disease (CD) are unknown. We investigated the long-term outcome of undiagnosed CD and whether the prevalence of undiagnosed CD has changed during the past 50 years.

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.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among older individuals in many parts of the world. The relative importance of genes and environment in the etiology of this major public health problem is not well understood.Objective: To investigate the impact of genetic and environmental factors.Participants: Living twins in the National Academy of Sciences-National Research Council World War II Veteran Twin Registry born between 1917 and 1927.Methods: Twins were surveyed for the known presence of macular degeneration. Enrolled twins underwent a standardized examination and fundus photography. Age-related macular degeneration evaluation was completed for 840 elderly male twins, 210 monozygotic and 181 dizygotic complete twin pairs, both concordant and discordant for presence or absence of AMD, and 58 singletons. A bivariate twin model incorporating initial screening ascertainment and age effectswasemployedtopartitionvariationinliabilitytoAMD and signs of maculopathy into additive genetic, common environment, and unique environment components.Main Outcome Measure: Heritability of AMD grade and signs of maculopathy based on clinical examination and fundus photographs.Results: Of the 840 twins, 331 had no signs of maculopa-thyand241hadearlysigns,while162hadintermediateAMD and 106 had advanced AMD. Heritability (additive genetic) estimates were significant for overall AMD grade (0.46) and for intermediate (0.67) and advanced (0.71) AMD. Significant unique environmental proportions of variance were also observed for these AMD variables (0.37, 0.19, and 0.24, respectively). Shared or common environmental contributions were not significant (0.05-0.17). For specific macular drusen and retinal pigment epithelial characteristics, significantgenetic(0.26-0.71)anduniqueenvironmental(0.28-0.64) proportions of variance were detected.

We evaluated the relation of education and intelligence in early adult life to cognitive function in a group of elderly male twins. The Army General Classification Test (AGCT) was administered to US armed forces inductees in the early 1940s. Fifty years later, as part of a study of dementia in twins, we tested the cognitive status of 930 of these men using the modified Telephone Interview for Cognitive Status (TICS-m). TICS-m scores obtained in later life were correlated with AGCT scores (r = 0.457) and with years of education (r = 0.408). Thus, in univariate analyses, the AGCT score accounted for 20.6% and education accounted for 16.7% of variance in cognitive status. However, these two effects were not fully independent. A multivariable model using AGCT score, education, and the interaction of the two variables as predictors of the TICS-m score explained 24.8% of the variance, a slightly but significantly greater proportion than was explained by either factor alone. In a separate analysis based on 604 pairs of twins who took the AGCT, heritability of intelligence (estimated by AGCT score) was 0.503. Although this study does not address the issue of education and premorbid IQ as risk factors for dementia, the findings suggest that basic cognitive abilities in late life are related to cognitive performance measures from early adult life (ie, education and IQ).

Medical records of the 15,924 twin-pairs in the National Academy of Sciences-National Research Council (NAS-NRC) twin registry were collected for an additional 16 years through 1994 when the surviving twins were aged 67 to 77 years. Compared with earlier analyses (Hrubec, Z, and Omenn, G. S., Alcohol. Clin. Exp. Res., 5:207-215, 1981), when subjects were aged 51 to 61, there were 23% more diagnoses of alcoholism (34.4 per 1,000 prevalence), 32% more diagnoses of alcoholic psychosis (5.4 per 1,000), and 25% more twins with liver cirrhosis (17.7 per 1,000). Overall, 5.3% of the cohort had at least one of the diagnoses related to alcoholism. Probandwise concordance rates (%) were: alcoholism-26.7 monozygotic (MZ), 12.2 dizygotic (DZ) (p < 0.0001); alcoholic psychosis-17.3 MZ, 4.8 DZ (p < 0.05); and cirrhosis-16.9 MZ, 5.3 DZ (p < 0.001). Concordance for any diagnosis related to alcoholism was 30.2 MZ, 13.9 DZ (p < 0.0001). Maximum-likelihood modeling indicated that approximately 50% of the overall variance was due to additive genetic effects; in all diagnosis categories, a totally environmental model gave a significantly poorer fit to the data. Bivariate and trivariate genetic analyses indicated most of the genetic liability for the organ-specific endpoints of psychosis and cirrhosis was due to the shared genetic liability for alcoholism. Once the shared variance with alcoholism was considered, there was no further shared genetic liability for psychosis and cirrhosis. Our results confirm Hrubec and Omenn's conclusion that there was significantly greater concordance in MZ twins-pairs for alcoholic psychosis and cirrhosis in the NAS-NRC twins, and concordance rates remained similar to those reported 16 years earlier. In contrast, we found most of the genetic liability to organ-specific complications of alcoholism was shared with the genetic liability for alcoholism per se; only a small portion of the genetic variance of the individual complications was independent of the genetic predisposition for alcoholism.