Background The contribution of hereditary factors to the causation of sporadic cancer is unclear. Studies of twins make it possible to estimate the overall contribution of inherited genes to the development of malignant diseases. Methods We combined data on 44,788 pairs of twins listed in the Swedish, Danish, and Finnish twin registries in order to assess the risks of cancer at 28 anatomical sites for the twins of persons with cancer. Statistical modeling was used to estimate the relative importance of heritable and environmental factors in causing cancer at 11 of those sites. Results At least one cancer occurred in 10,803 persons among 9512 pairs of twins. An increased risk was found among the twins of affected persons for stomach, colorectal, lung, breast, and prostate cancer. Statistically significant effects of heritable factors were observed for prostate cancer (42 percent of the risk may be explained by heritable factors; 95 percent confidence interval, 29 to 50 percent), colorectal cancer (35 perce...

Environmental and Heritable Factors in the Causation of Cancer — Analyses of Cohorts of Twins from Sweden, Denmark, and Finland

Context There are many published twin studies of schizophrenia. Although these studies have been reviewed previously, to our knowledge, no review has provided quantitative summary estimates of the impact of genes and environment on liability to schizophrenia that also accounted for the different ascertainment strategies used. Objective To calculate meta-analytic estimates of heritability in liability and shared and individual-specific environmental effects from the pooled twin data. Data Sources We used a structured literature search to identify all published twin studies of schizophrenia, including MEDLINE, dissertation, and books-in-print searches. Study Selection Of the 14 identified studies, 12 met the minimal inclusion criteria of systematic ascertainment. Data Synthesis By using a multigroup twin model, we found evidence for substantial additive genetic effects—the point estimate of heritability in liability to schizophrenia was 81% (95% confidence interval, 73%-90%). Notably, there was consistent evidence across these studies for common or shared environmental influences on liability to schizophrenia—joint estimate, 11% (95% confidence interval, 3%-19%). Conclusions Despite evidence of heterogeneity across studies, these meta-analytic results from 12 published twin studies of schizophrenia are consistent with a view of schizophrenia as a complex trait that results from genetic and environmental etiological influences. These results are broadly informative in that they provide no information about the specific identity of these etiological influences, but they do provide a component of a unifying empirical basis supporting the rationality of searches for underlying genetic and common environmental etiological factors.

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Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies.

Height, weight, and body mass index (BMI) were assessed in a sample of 1974 monozygotic and 2097 dizygotic male twin pairs. Concordance rates for different degrees of overweight were twice as high for monozygotic twins as for dizygotic twins. Classic twin methods estimated a high heritability for height, weight, and BMI, both at age 20 years (.80, .78, and .77, respectively) and at a 25-year follow-up (.80, .81, and .84, respectively). Height, weight, and BMI were highly correlated across time, and a path analysis suggested that the major part of that covariation was genetic. These results are similar to those of other twin studies of these measures and suggest that human fatness is under substantial genetic control.

A twin study of human obesity

The aim of this study was to explore, in a large and non-censored twin cohort, the nature (i.e., additive versus non-additive) and magnitude (i.e., heritability) of genetic influences on inter-individual differences in hu- man longevity. The sample comprised all identified and traced non-emigrant like-sex twin pairs born in Denmark during the period 1870-1900 with a zygosity diagnosis and both members of the pairs surviving the age of 15 years. A total of 2872 pairs were included. Age at death was obtained from the Danish Central Person Register, the Danish Cause-of-Death Register and various other registers. The sample was almost non-censored on the date of the last follow-up (May 1, 1994), all but 0.6% had died, leaving a total of 2872 pairs for analysis. Proportions of variance attributable to genetic and environmental factors were assessed from variance-covariance matrices using the structural equation model approach. The most parsi- monious explanation of the data was provided by a model that included genetic dominance (non-additive genetic ef- fects caused by interaction within gene loci) and non-shared environmental factors (environmental factors that are in- dividual-specific and not shared in a family). The heri- tability of longevity was estimated to be 0.26 for males and 0.23 for females. The small sex-difference was caused by a greater impact of non-shared environmental factors in the females. Heritability was found to be constant over the three 10-year birth cohorts included. Thus, longevity seems to be only moderately heritable. The nature of ge- netic influences on longevity is probably non-additive and environmental influences non-shared. There is no evi- dence for an impact of shared (family) environment.

https://user.demogr.mpg.de/jwv/pdf/vaupel-hg-97-1996-3.pdf

The heritability of human longevity: A population-based study of 2872 Danish twin pairs born 1870–1900

Concern is building about high rates of schizophrenia in large cities, and among immigrants, cannabis users, and traumatized individuals, some of which likely reflects the causal influence of environmental exposures. This, in combination with very slow progress in the area of molecular genetics, has generated interest in more complicated models of schizophrenia etiology that explicitly posit geneenvironment interactions (EU-GEI. European Network of Schizophrenia Networks for the Study of Gene Environment Interactions. Schizophrenia aetiology: do geneenvironment interactions hold the key? [published online ahead of print April 25, 2008] Schizophr Res; S09209964(08) 00170‐9). Although findings of epidemiological gene-environment interaction (G 3 E) studies are suggestive of widespread gene-environment interactions in the etiology of schizophrenia, numerous challenges remain. For example, attempts to identify gene-environment interactions cannot be equated with molecular genetic studies with a few putative environmental variables ‘‘thrown in’’: G 3 E is a multidisciplinary exercise involving epidemiology, psychology, psychiatry, neuroscience, neuroimaging, pharmacology, biostatistics, and genetics. Epidemiological G 3 E studies using indirect measures of genetic risk in genetically sensitive designs have the advantage that they are able to model the net, albeit nonspecific, genetic load. In studies using direct molecular measures of genetic variation, a hypothesis-driven approach postulating synergistic effects between genes and environment impacting on a final common pathway, such as ‘‘sensitization’’ of mesolimbic dopamine neurotransmission, while simplistic, may provide initial focus and protection against the numerous false-positive and false-negative results that these investigations engender. Experimental ecogenetic approaches with randomized assignment may help to overcome some of the limitations of observational studies and allow for the additional elucidation of underlying mechanisms using a combination of functional enviromics and functional genomics.

/pdf/gene-environment-interactions-in-schizophrenia-review-of-2v81y4jvsa.pdf

Gene-Environment Interactions in Schizophrenia: Review of Epidemiological Findings and Future Directions

A description is given of the Danish Twin Register which is based on the total twin population born in Denmark in the years 1870-1910 with a more recent addition of all same-sexed pairs from the period 1911-1920. Twins belonging to pairs where one or both partners are found to have died before attaining the age of six years are disregarded in the more intensive studies whereas the remaining part of the twin population is being followed by periodical inquiries. The methods used in the collection of the material, in the establishment of the zygosity diagnosis and in specific investigations of selected diseases and abnormalities are described and discussed. A survey is given of the more important results of the research based on the Register. In the group of somatic diseases, greatest attention has so far been paid to malignant growths, diabetes mellitus and peptic ulcer. A number of psychiatric disorders and deviations are at present being studied with schizophrenia and criminality as the first subjects for intensive research. Some of the main results obtained are given as illustrations of the potentialities and scope of this approach to the application of twin studies in a broad variety of research areas.

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The Danish twin register.

An epidemiological study of the first admission rate for mania was carried out in London and Aarhus. The case registers in these two centres were used to conduct a retrospective study of case notes covering several years, and a screening procedure was used for the prospective collection of new cases over the course of one year. The annual incidence of mania was found to be virtually identical in both centres. The retrospective study gave a figure of 2-6 per 100,000 population in both Aarhus and London. But the London sample was found to contain 45 per cent of immigrants in contrast to the Aarhus sample in which only a negligible proportion were born outside Denmark. Male West Indians, in particular, were over-represented in the London sample.

A cross-national epidemiological study of mania.

A group of children, of whom one parent is a monozygotic (MZ) schizophrenic twin, has been compared with a group of children of whom one parent is a normal MZ twin to a schizophrenic twin. A third group, of whom One parent is a normal dizygotic (DZ) twin to a schizophrenic twin, was examined in order to function as a sort of control group. This third group, however, was after age correction too small to supply reliable information.

In no case was the other parent psychotic.

In group 1, consisting of 47 children, 3 schizophrenic cases and one suicide were found, giving a morbidity risk of 9.4 per cent after age correction.

In group 2, consisting of 25 children, there were also 3 schizophrenic cases. The morbidity risk after age correction was 12.3 per cent (not a significant difference from group 1).

The present investigation gives no support to the hypothesis that environmental factors, associated with being reared by a schizophrenic parent, should cause more schizophrenia in the offspring, since controls reared by a non-schizophrenic had the same morbidity risk.

The result could be explained as due to factor(s) equally present in the schizophrenic MZ twins and their normal co-twin. As a pair of MZ twins are genetically identical, a hereditary factor is the most likely explanation.

However, the present material is of such limited size that no conclusion can be drawn.

Of the 6 psychiatric cases 5 were females. The twin-parents in the 6 cases were 4 female and 2 male, and 4 of these twin pairs were discordant for schizophrenia. From the precipitating factors, symptomatology and course of illness described in these cases, the question arises whether some cases of schizophrenia are (almost) only genetically determined, while in other cases both genetic and environmental factors are necessary for the outbreak of a schizophrenic psychosis.

Psychoses in the Offspring of Schizophrenic Monozygotic Twins and their Normal Co-Twins

From among a population of same-sexed Danish twins born 1870-1920 a total of seventy-eight probands with process-schizophrenia were selected. Among the co-twins of twenty-five MZ probands nine were found to have schizophrenia, and a further five co-twins had presented schizophrenic traits; the corresponding figures for the co-twins of forty-five DZ probands were eight and five respectively. In eight probands zygosity could not be determined with sufficient certainty. If partners with schizophreniform, paranoid or atypical psychoses are accepted as concordant, the probandwise MZ and DZ concordance rates will be 0.56 and 0.26. This difference is significant, which in agreement with earlier twin studies indicates that genetic factors influence population variability with regard to schizophrenia. The actual value of the MZ concordance rate in the present study is, however, in the lower range of all previously obtained figures, in this respect corresponding with two recent Scandinavian studies. It is characteristic of these three studies as opposed to all others that the probands have been selected from a total population.

A Danish Twin Study of Schizophrenia

A sex-chromatin and chromosome study of patients with hypogonadal symptoms and signs was made. Three of the 14 men were found to be cases of chromatin positive Klinefelter's Syndrome, two with 47 chromosomes and sex-chromosomes XXY, one with 48 chromosomes and sex-chromosomes XXXY.

Case histories of the three patients with Klinefelter's Syndrome are presented, and the psychopathology of these cases discussed. The similarities in the three cases are immaturity, lack of initiative, dependency on others, sensitivity, a tendency to reactive depressions, I. Q. low in the normal range, and for the patient with 48 chromosomes, sex-chromosomes XXXY, I. Q. below normal range, sex identification problems, feelings of insufficiency, and a tendency to self-reference. Two of the three patients suffered from psychogenic paranoid psychoses, and one had the diagnosis of alcoholism and character disorders.

It is hypothesized that patients with Klinefelter's Syndrome and with the intelligence and type of personality characteristic of this syndrome may easily develop reactive depressions or psychogenic paranoid psychosis and easily get classified as character disorders and depressive neuroses.

Margit Fischer

Papers

The Danish twin register.

A cross-national epidemiological study of mania.

Psychoses in the Offspring of Schizophrenic Monozygotic Twins and their Normal Co-Twins

A Danish Twin Study of Schizophrenia

Sex-Chromatin and Sex-Chromosome Abnormalities in Male Hypogonadal Mental Patients