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Context: Anorexia nervosa (AN) is a serious mental illness with marked morbidity and mortality., Objective: To explore the prevalence, heritability, and prospectively assessed risk factors for AN in a large population-based cohort of Swedish twins., Design: During a 4-year period ending in 2002, all living, contactable, interviewable, and consenting twins in the Swedish Twin Registry (N = 31 406) born between January 1, 1935, and December 31, 1958, underwent screening for a range of disorders, including AN. Information collected systematically in 1972 to 1973, before the onset of AN, was used to examine prospective risk factors for AN., Setting: Population-based sample of twins in Sweden., Participants: Cases of AN were identified as those individuals who met full DSM-IV criteria by means of clinical interview of the Swedish Twin Registry, who had a hospital discharge diagnosis of AN, or who had a cause-of-death certificate including an AN diagnosis., Results: The overall prevalence of AN was 1.20% and 0.29% for female and male participants, respectively. The prevalence of AN in both sexes was greater among those born after 1945. Individuals with lifetime AN reported lower body mass index, greater physical activity, and better health satisfaction than those without lifetime AN. Anorexia nervosa was inversely associated with the development of overweight (odds ratio, 0.29; 95% confidence interval [CI], 0.16-0.54 [P<.001]). The heritability of narrowly defined DSM-IV AN (additive genetic effects) was estimated to be a(2) = 0.56 (95% CI, 0.00-0.87), with the remaining variance attributable to shared environment (c(2) = 0.05; 95% CI, 0.00-0.64) and unique environment (e(2) = 0.38; 95% CI, 0.13-0.84). Neuroticism measured about 3 decades before the diagnostic assessment was significantly associated with the development of later AN (odds ratio, 1.62; 95% CI, 1.27-2.05 [P<.001])., Conclusions: The prevalence of AN was higher in both male and female participants born after 1945. Individuals who survive AN and who no longer have body mass indexes in the AN range appear to be at lower risk for the development of overweight. Prospectively assessed neuroticism was associated with the subsequent development of AN, the liability to which is under considerable genetic influence.