Familial factors have previously been implicated in the etiology of fatigue, of which a significant proportion is likely attributable to genetic influences. However, family studies have primarily focused on chronic fatigue syndrome, while univariate twin studies have investigated broader fatigue phenotypes. The results for similar fatigue phenotypes vary between studies, particularly with regard to sex-specific contributions to the heritability of the traits. Therefore, the current study aims to investigate the familiality and sex-specific effects of fatigue experienced over the past few weeks in an older Australian population of 660 monozygotic (MZ) twin pairs, 190 MZ singleton twins, 593 dizygotic (DZ) twin pairs, and 365 DZ singleton twins. Higher risks for fatigue were observed in MZ compared to DZ co-twins of probands with fatigue. Univariate heritability analyses indicated fatigue has a significant genetic component, with a heritability (h2) estimate of 40%. Sex-specific effects did not significantly contribute to the heritability of fatigue, with similar estimates for males (h2 = 41%, 95% CI [18, 62]) and females (h2 = 40%, 95% CI [27, 52]). These results indicate that fatigue experienced over the past few weeks has a familial contribution, with additive genetic factors playing an important role in its etiology.

To identify large numbers of twins affected by chronic disease as potential subjects for studies of environmental and genetic chronic disease determinants, we advertised for affected twins over the period 1980–91 in newspapers across North America. Responses were received from 17 245 twin pairs in which cases of cancer or other chronic disease had occurred. To assess the representativeness of affected twins identified by advertising, we evaluated the pattern of reporting, compared the cases identified to the number of cases estimated to be prevalent among all North American twins, compared the cases to population-based singleton case series, compared the healthy co-twins to population-based samples of healthy persons, assessed the impact on ascertainment of opinions about disease causation, compared the pattern of prospective to retrospective ascertainment of disease in the originally unaffected co-twins of cases, and compared the results of the prospective ascertainment of disease in co-twins to comparable published estimates. Youth, gender, zygosity, education, and disease concordance were found to be overall determinants of ascertainment. Disease-discordant DZ twins appeared to be modestly underascertained. While somewhat better educated, both concordant and discordant pairs were judged to be reasonably representative of affected non-Hispanic white North American twin pairs of comparable status, ie of comparable age, sex, race, and zygosity. If interpreted with caution, the concordance patterns of such twins can be used to generate genetic hypotheses, but should not be the basis of definitive heritability analyses. We conclude that advertising offers a method of identifying pairs of twins that can serve as subjects for studies designed to identify disease determinants. Twin Research (2000) 3, 33–42.