Linda A. Corey

A population-based twin study in women of smoking initiation and nicotine dependence

BACKGROUNDnThe development of drug dependence requires prior initiation. What is the relationship between the risk factors for initiation and dependence?nnnMETHODSnUsing smoking as a model addiction, we assessed smoking initiation (SI) and nicotine dependence (ND) by personal interview in 1898 female twins from the population-based Virginia Twin Registry. We developed a twin structural equation model that estimates the correlation between the liability to SI and the liability to ND, given SI.nnnRESULTSnThe liabilities to SI and ND were substantially correlated but not identical. Heritable factors played an important aetiological role in SI and in ND. While the majority of genetic risk factors for ND were shared with SI, a distinct set of familial factors, which were probably partly genetic, solely influenced the risk for ND. SI was associated with low levels of education and religiosity, high levels of neuroticism and extroversion and a history of a wide range of psychiatric disorders. ND was associated with low levels of education, extroversion, mastery, and self-esteem, high levels of neuroticism and dependency and a history of mood and alcohol use disorders.nnnCONCLUSIONSnThe aetiological factors that influence SI and ND, while overlapping, are not perfectly correlated. One set of genetic factors plays a significant aetiological role in both SI and ND, while another set of familial factors, probably in part genetic, solely influences ND. Some risk factors for SI and ND impact similarly on both stages, some act at only one stage and others impact differently and even in opposite directions at the two stages. The pathway to substance dependence is complex and involves multiple genetic and environmental risk factors.

A multivariate genetic analysis of the use of tobacco, alcohol, and caffeine in a population based sample of male and female twins

Numerous epidemiologic studies in the past few decades have consistently demonstrated positive associations between the use of various psychoactive substances, both licit and illicit. This association could be due to shared genetic and/or shared environmental risk factors. This study uses multivariate structural equation modeling to determine the sources of covariation between the use of tobacco, alcohol, and caffeine, the three most commonly consumed psychoactive substances. In particular, we wish to clarify the extent to which genetic and environmental risk factors are shared across these three substances versus are substance specific in their effect. The sample, consisting of data collected from members of the population-based Virginia Twin Registry, consists of 774 monozygotic and 809 dizygotic male and female twin pairs. Our results demonstrate that genetic and individual specific environmental factors that are shared between these three substances account for a modest proportion of the total variance. For example, shared genetic risk factors across the three substances in males and females account for between 7 and 28% of the total variance in liability and 12-56% of the genetic variance. Common familial environment appears to play little or no role. Underlying genetic and individual environmental risk factors produce liability to (poly)substance use in general; substance specific factors also play an important etiologic role.

Univariate genetic analyses of epilepsy and seizures in a population-based twin study: The Virginia twin registry

The purpose of this study was to examine the roles of genetic and environmental factors in the etiology of epilepsy and seizures in twins ascertained from the Virginia Twin Registry. Health history information on twins was collected by questionnaire. Concordance rates were calculated and used to estimate degree of concordance for seizure types in monozygotic (MZ) and dizygotic (DZ) twin pairs. Univariate twin analyses were performed for each epilepsy and seizure type to determine models which best explained observed variation. Health history information concerning epilepsy and febrile seizure occurrences was provided by members of 8,655 twin pairs; 6,684 of these supplied additional information reporting absence, complex partial, tonic‐clonic, and unspecified seizures. Models including additive genetic and unique environmental factors best explained febrile seizures, epilepsy, complex partial seizures, and unspecified seizures. For complex partial seizures, however, the contributions of genetic and environmental effects did not vary across gender. These results show that, under univariate analysis methods, genetic factors played an important role in the expression of seizures in epilepsy, febrile seizures, unspecified seizures, and complex partial seizures. Additional support for these findings was provided by the concordance results for all categories except male twins reporting complex partial seizure occurrence. However, environmental influences still remained an important factor in seizure expression in these specific categories. Genet. Epidemiol. 15:33–49,1998.

Social inequality and assortative mating: cause or consequence?

Johnsonet al. (Behav. Genet.17:1–7, 1987) have interpreted an apparent decline in assortative mating for educational attainment in Hawaii as being a consequence of increased social mobility and increased access to higher education. Data on the educational attainments of adult twin pairs and their spouses from the Virginia twin registry are reported which give no indication of a major decline in the intensity of assortative mating. A previous study of a Norwegian population (Heathet al., Behav. Genet.15:349–369, 1985), in which an increase in equality of educational opportunity had been documented (Heathet al., Nature314:734–736, 1985), observed remarkable constancy of the marital correlation for educational attainment. There is thus little evidence that decreases in social inequality in a society lead to a decline in assortative mating.

A genetic analysis of taste threshold for phenylthiocarbamide.

Taste threshold for phenylthiocarbamide (PTC) was measured in 393 offspring from the families of 85 monozygotic (MZ) twin pairs. PTC scores were bimodally distributed with modes at one and eight and the antimode at five. Because of the non-normality of the distribution, a jackknife procedure was used to obtain 95% confidence intervals for the estimates of genetic, maternal, and environmental parameters. Analyses which assumed no epistasis and which included additive genetic effects revealed that 37.9% of the observed variation in PTC threshold was due to additive genetic effects, 16.6% was due to dominance effects, 14.2% was due to maternal effects, 13.7% was due to a common sibship environment, and 17.6% was due to random environmental effects, yielding a broad sense heritability of 0.55 for the threshold ability to taste PTC. Analyses which did not include additive genetic effects revealed 26.6% of the observed variance was due to dominance effects, 23.6% to maternal effects, and 49.8% to environmental effects at the 0.67 confidence levels, but that environmental factors accounted for 72.4% and dominance effects for 23.6% of the observed variation at the 95% level.

Epilepsy and seizure occurrence in a population-based sample of Virginian twins and their families

Epilepsy and seizure occurrence was assessed in a large, population-based sample of Virginian twins and their families. Medical history information on twins and their relatives was collected by questionnaire and used to estimate prevalence of seizures and epilepsy for this sample. Health history information was available on 16,634 twins and their families. Lifetime prevalence of a history of seizures ranged from < 1 to 5%. Concordance rates were larger in monozygotic (MZ) than dizygotic (DZ) pairs overall, however, significant differences between the zygosities were only noted for Caucasian twins. To facilitate interpretation of results, the sample was partitioned into two age groups: 16-35 years and > 35 years of age. In the first age category of twins, significant differences were observed for the following seizure types; epilepsy (0.30 and 0.13, p <0.03), febrile seizures (0.39 and 0.12, p <0.001), and other convulsions/seizures (0.28 and 0.01, p < 0.001). While for twins in the second age category, only the comparison for febrile seizures (0.42 and 0.14, p < 0.001) resulted in a significant difference between zygosities. A family history of seizures was reported in 215 (35.1%) of the 613 seizure positive probands. Increased risk of seizures (1.88-4.64) among relatives of affected versus unaffected individuals was also observed.

Quinacrine mustard and nucleolar organizer region heteromorphisms in twins

Patterns of NOR activity in 640 metaphase spreads from twelve monozygotic (MZ) and eight dizygotic (DZ) twin pairs were studied to evaluate the heritability of this chromosomal heteromorphism. NORs were stained by a modification of the Ag-AS technique and counterstained with quinacrine mustard dihydrochloride to facilitate chromosome identification and assess their value in zygosity determination. In this study, all karyotypes were read blind with respect to zygosity and pair membership. A discriminant function analysis of pair score differences in MZ and DZ twins revealed that, in our sample, the probability of accurately determining zygosity with NOR scores was 0.93 and with QFQ scores was 0.99. We conclude that NOR and QFQ scores are highly heritable and of great value in zygosity determination. Data were collected from 687 metaphase spreads on the frequency with which an acrocentric chromosome was found in a satellite association. A significant correlation was found between this frequency and the degree of Ag-AS stain of the NOR. This study, therefore, confirms previous results showing that a high degree of NOR activity is found in those chromosomes most often involved in satellite associations.

The human X‐chromosome and the levels of serum immunoglobulin M

The serum concentrations of immunoglobulins G, A and M were measured in a sample of 93 pairs of monozygotic twins, their spouses, and their offspring. The hypothesis that the human X‐chromosome carries genes which control the levels of immunoglobulin M was tested with three different approaches. Our results indicate that environmental factors are primarily responsible for the observed variation in the levels of IgG and IgA. The variance of IgM seems to be mostly the result of X‐linked gene effects, with women having higher IgM levels than men.

A model for the analysis of mate selection in the marriages of twins: application to data on stature.

Analysis of the multiple correlations in body height within a sample of 117 monozygotic twin pairs and their spouses confirmed the existence of a high degree of assortative mating. However, the data also revealed an underlying asymmetry in the mate selection process. With respect to height, male twins were more selective than were members of female pairs, and among male twin pairs, those who were intermediate in height appeared to make the greatest contribution to the observed pattern of nonrandom mating. Because of their magnitude and potential asymmetry, the effects of phenotypic correlations between the spouses of related individuals must be correctly specified in any rigorous quantitative genetic analysis that extends beyond the nuclear family unit.