The occurrence and characteristics of auras in a large epilepsy cohort.

OBJECTIVES: Despite several studies, estimates of the frequency with which auras occur in conjunction with epilepsy continue to be imprecise. The aim of this study was to assess the occurrence and characteristics of auras in a large population-based epilepsy cohort. MATERIALS AND METHODS: Subjects with verified epilepsy were recruited from population-based twin registries in the USA, Denmark and Norway. Using a structured interview in which a list of auras was provided, subjects were asked about the warning symptoms preceding their epileptic attacks. RESULTS: 31% of the total sample (n = 1897) and 39% of those with active epilepsy (n = 765) had experienced an aura. Six percent reported more than one type. Non-specified auras were most frequently reported (35%), followed by somatosensory (11%) and vertiginous (11%). While the majority of those reporting auras (59%) had focal epilepsies, auras of a mostly non-specific nature were experienced by 13% of those with generalized epilepsies. CONCLUSION: Auras serve an important purpose in that they may prevent seizure-related injuries and could provide an indication as to where the seizures originate. The occurrence of auras often is underestimated, especially in children and those with learning disabilities.

Genetic screening of Scandinavian families with febrile seizures and epilepsy or GEFS+.

BACKGROUND: Mutations in the three genes SCN1A, SCN1B and GABRG2, all encoding subunits of ion channels, have been known to cause generalized epilepsy with febrile seizures plus (GEFS+) in families of different origin. OBJECTIVE: To study the occurrence of mutations in these genes in families with GEFS+ or a GEFS+ resembling phenotype of Scandinavian origin. MATERIAL AND METHODS: We performed linkage analysis in 19 Scandinavian families with a history of febrile seizures (FS) and epilepsy or GEFS+. Where linkage could not be excluded, the genes of interest were sequenced. RESULTS: We identified only one mutation in SCN1A, which seems to be a rare variant with no functional consequence. CONCLUSION: This suggests that mutations in these three genes are not a prevalent cause of familial cases of FS and epilepsy or GEFS+ in Scandinavia.

Genetic models for the analysis of data from the families of identical twins.

Genetic models are described which exploit the unique relationships that exist within the families of identical twins to obtain weighted least squares estimates of additive, dominance and epistatic components of genetic variance as well as estimates of the contributions of X-linked genes, maternal effects and three sources of environmental variation. Since all of the relationships required to achieve a resolution of these variance components are contained within each family unit, the model would appear to be superior to previous approaches to the analysis of quantitative traits in man.

Maternal and Reciprocal Effects on Seedling Characters in ARABIDOPSIS THALIANA (L.) Heynh.

Five early growth characters were examined in six races of Arabidopsis thaliana (L.) Heynh, their reciprocal F(1) hybrids (1974) and F(1) by tester hybrids, using a seventh race as a paternal tester. Three of the five characters were also examined at two nutrient levels in reciprocal F(1) hybrids (1972) of all seven races. Analyses of F(1) and F(1) by tester hybrids revealed significant maternal effects in all characters examined in F(1) hybrids (1972) and in root length and plant weight of F(1) (1974) and F(1) by tester hybrids. Significant reciprocal effects were found for plant weight in F(1) by tester hybrids and for seed weight, percentage of germination and root length in F(1) (1974) and F(1) by tester hybrids. The presence of significant maternal and/or reciprocal components in both F(1) (1974) and F(1) by tester diallels suggests that differences in maternal cytoplasm rather than maternal genotype per se were responsible for much of the variation resulting from these non-direct genetic effects.

Longitudinal population-based twin study of retrospectively reported premenstrual symptoms and lifetime major depression.

OBJECTIVE: While family and twin studies suggest that retrospectively reported premenstrual symptoms are heritable, these studies have not accounted for the unreliability of such measures. In addition, we know little about the relationship of the familial risk factors for premenstrual symptoms and major depression. METHOD: Lifetime major depression and premenstrual-related tiredness, sadness, and irritability were assessed twice over 6 years in 1,312 menstruating female twins ascertained from a population-based twin register. A twin-measurement model--which permits estimation of the etiologic roles of genetic and environmental factors with correction for errors of measurement or short-term temporal fluctuations--was applied to these data. RESULTS: A single premenstrual symptom factor was found that was moderately stable over time. The best-fitting twin-measurement model estimated the heritability of the stable component of premenstrual symptoms at 56% and showed no impact of family-environmental factors. A bivariate twin-measurement model estimated that the genetic and environmental risk factors for lifetime major depression contributed only modestly to the etiology of premenstrual syndrome. No evidence was found for significant biases in the twin method. CONCLUSIONS: Retrospectively reported premenstrual-related symptoms of depression and anxiety are moderately stable over time and, when correction is made for this level of stability, substantially heritable. The genetic and environmental risk factors for these premenstrual symptoms and lifetime major depression are not closely related.

Evidence for a genetic predisposition for status epilepticus.

The role of genetic factors in determining risk for status epilepticus (SE) was examined in twins identified using the population-based Virginia Twin Registry. Concordance rates for SE were 0.38 for monozygotic (MZ) and 0.00 for dizygotic (DZ) twins, with the rate in MZs being significantly increased over DZs. The prevalence of SE in MZ co-twins of affected individuals was as high as 0.55. Clinical presentation of SE was evaluated, and no association was found between occurrence of SE and age at onset or seizure etiology. Genetic factors contribute to risk for SE.

The occurrence of epilepsy and febrile seizures in Virginian and Norwegian twins.

Twin studies provide an efficient method for examining the importance of genetic and environmental factors in the etiology of disorders such as epilepsy. Population-based twin registries are especially valuable for studies of this type since effects of reporting and self-selection biases on the resulting data are minimized. Among 14,352 twin pairs contained in the Virginia and Norwegian twin panels for whom questionnaire information was available, there was a history of epilepsy in one or both members of 286 pairs; febrile seizures were reported in 257 pairs. Analyses of questionnaire data revealed no significant differences in concordance rates between Virginian and Norwegian twins for either epilepsy or febrile seizures. Probandwise concordance rates for epilepsy were 0.19 in monozygotic twins and 0.07 in dizygotic twins. Analogous rates for febrile seizures were 0.33 (monozygotic) and 0.11 (dizygotic). These results provide further evidence that genetic factors do have a role in the expression of epilepsy and febrile seizures.

Common fragile site expression in lymphocytes from an individual mosaic for trisomy 8.

During the course of a survey of fragile site expression in lymphocytes from twins one member of a dizygotic pair was found to be mosaic for trisomy 8. One hundred fifty metaphases from this individual were analyzed (100 treated with aphidicolin and 50 untreated); 43% were 46,XY and 57% 46,XY,+8. No differences were observed between the treated and control cultures in either the proportions of normal and trisomic metaphases or the overall or specific fragile site expression in the normal and trisomic cells.

Histopathology of endocervical infection caused by Chlamydia trachomatis, herpes simplex virus, Trichomonas vaginalis, and Neisseria gonorrhoeae.

We determined the histologic correlates of clinically identified mucopurulent cervicitis, culture-proven cervical infection with Chlamydia trachomatis, Neisseria gonorrhoeae, herpes simplex virus (HSV), and vaginal infection with Trichomonas vaginalis by examining cervical biopsies from 83 women. Clinical mucopurulent cervicitis and culture-documented infection with one or more of these pathogens correlated histologically with intraepithelial neutrophils, reactive endocervical cells, edema, luminal neutrophils, and with several deeper tissue changes such as extensive and dense subepithelial inflammation, granulation tissue, and necrotic ulceration. Focal loss of surface columnar cells and spongiosis were also correlated with culture-confirmed infection. Well-formed germinal centers were seen in biopsies from 14 of 21 patients (67%) with C trachomatis infection alone, but in none of 17 patients with infections other than C trachomatis (P less than 0.001). A predominantly plasmacytic infiltrate was also significantly associated with chlamydial infection. Necrotic ulcers overlying a predominantly lymphocytic infiltrate were seen in six of nine patients (67%) with HSV infection alone but in only two of 40 patients (5%) with other infections (P less than 0.001). Marked inflammatory changes were not seen in the patients infected with N gonorrhoeae. The organism T vaginalis was not associated with any endocervical pathology. If these results are confirmed by prospective studies, they suggest that pathologists should alert clinicians to the possibility of recent or current infection with C trachomatis or HSV when cervical biopsies show the above changes. The loss of surface columnar epithelium with HSV, chlamydial, and gonococcal infection offers a possible explanation for the reported association of these infections with increased risk of acquiring human immunodeficiency virus infection.

The epidemiology of pregnancy complications and outcome in a Norwegian twin population.

OBJECTIVE: To measure the contribution of genetic factors to selected pregnancy complications, including miscarriage, twinning, hypertension-toxemia, and nausea-vomiting. METHODS: Information on 22,241 pregnancies of 8675 female twins or spouses of male twins was obtained by questionnaire from members of the population-based Norwegian Twin Panel. Comparisons of observed tetrachoric correlations were used to assess the importance of genetic influences on the variables examined. RESULTS: Pregnancy history information was provided by both members of 830 monozygotic and 902 dizygotic female twin pairs and by the spouses of both members of 459 monozygotic and 464 dizygotic male twin pairs. The incidence of twin pregnancy in general, and of opposite-sexed twins in particular, found among dizygotic twin women was nearly twice that observed for any other group. Monozygotic female twin pairs were more concordant than dizygotic female twin pairs for the occurrence of miscarriage, nausea or vomiting during pregnancy, and hypertension or overt toxemia. A similar pattern of twin similarity was observed for the use of certain medications during pregnancy including vitamins, aspirin, and nausea medication. CONCLUSIONS: Maternal genetic factors make an important contribution to a predisposition for dizygotic twinning, contribute to the risk of miscarriage, and appear to determine, in part, whether a woman experiences nausea-vomiting or hypertension-toxemia during pregnancy. In addition, health-seeking behaviors of women during pregnancy, as reflected by the use of several classes of medication, appear to be influenced somewhat by genetic 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.

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.

Self-reported periodontal disease in a Virginia twin population.

To investigate the contribution of genetic factors in the etiology of periodontal disease, questionnaire data were collected on 4,908 twin pairs included in the population-based Virginia Twin Registry. A history of periodontal disease was reported in 420 individuals who were members of 116 monozygotic (MZ) and 233 dizygotic (DZ) twin pairs. The mean age at diagnosis in this sample was 31.4 +/- 0.7 years and was significantly earlier in females than males (30.1 vs. 33.0 years, P < 0.025). Proband-wise concordance rates were 0.38 for MZ and 0.16 for DZ twins. There were no differences in concordance rate between same and opposite-sexed dizygotic twins. These findings provide evidence that genetic factors make an important contribution to risk for adult-onset periodontal disease.

Fatty acid variability of plasma lipids and cholesteryl esters in adult male twins and their brothers.

Variation in the fatty acid composition of fasting plasma lipids and of cholesteryl esters was studied in 69 sets of adult male twins and 25 of their brothers. Genetic variances were estimated using the twin model. In general, monozygotic (MZ) twins were characterized by the smallest within-pair variance, and brothers of twins by the largest. Variation within dizygotic pairs fell imtermediate to that of MZ twins and brothers. The present study did not reveal consistent significant (P greater than 0.05) genetic variation in plasma fatty acids from total plasma lipids or cholesteryl esters.

Predictors of problem drinking and alcohol dependence in a population-based sample of female twins.

OBJECTIVE: To identify characteristics associated with problem drinking (PD) and alcohol dependence (AD) in women. METHOD: Subjects were 2,163 white women aged 17-55 from the population-based Virginia Twin Registry. Measures were selected from a clinical interview and questionnaires to reflect five domains associated with alcoholism in prior studies; demographic characteristics, personality, health, and personal and family history of psychopathology. Logistic and linear regression analyses were used to predict PD and DSM-III-R defined AD. RESULTS: Multiple regression models accounted for 19% of the variance in PD (significant predictors included: higher parental education-particularly among younger women, being the primary breadwinner, less frequent church attendance, higher scores on measures of neuroticism, extraversion and interpersonal dependency, history of major depression and social phobia, paternal PD and maternal treatment for emotional problems); 9% of the variance in diagnosis of AD (predicted by generalized anxiety, paternal depression and maternal PD); and 20% of the variance in number of symptoms of AD (predicted by the interaction of younger age and less-educated parents, higher neuroticism and mastery, lower optimism, generalized anxiety and agoraphobia, and maternal PD). CONCLUSIONS: Personality characteristics and parental psychopathology are important predictors of PD and AD independent of their effect on risk for affective and anxiety disorders. Many characteristics found to be associated with PD and AD in bivariate analyses were not significant when considered in the context of other predictors. Future studies of the etiology of alcoholism among women should simultaneously study measures from a variety of domains.

A study of dietary intake in adult monozygotic twins.

As a part of a study of the dietary habits of monozygotic twins, a nutrition survey including a 24-hour dietary recall interview and a three-day dietary diary was conducted on the members of 15 male and 13 female pairs of identical Caucasian twins ranging from 25 to 61 years of age. In this study, overall mean caloric, protein, fat, and carbohydrate intake of males was significantly greater than females. Members of male twin pairs also tended to be more similar than female twins in mean intake of all major nutrient groups. In general, the observed differences in overall intake between males and females were maintained even after adjustment of body weight. Male twins were characterized by greater similarity in intake of sodium and potassium; however, there was no consistent difference in the degree of correlation in intakes of members of male and female twins for either iron, calcium or phosphorus.

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.

Determinants of ridge counts in MZ twin kinships.

The inheritance of total ridge count (TRC) was studied in 967 individuals from the families of 111 pairs of MZ twins. The sample included data on 47 male half-sibships with 227 offspring and 64 female half-sibships with 306 offspring. The males in this sample had a mean ridge count of 135 +/- 2 and the females a mean ridge count of 124 +/- 2. The distribution of scores for females showed evidence for significant skewness. For this reason, prior to the analysis, the data were corrected for sex and adjusted to normality using a power transformation. Nested analyses of variance were performed on the ridge counts from male and female half-sibships separately to derive estimates of among, between, and within-variance components. These estimates were then used in a nonlinear least squares program to estimate genetic and environmental parameters and to determine the goodness of fit of various models. A model which included additive genetic and dominance effects could not be rejected (P = 0.67) but did not fit the data as well as a simple additive genetic-random environmental model (P = 0.81). The addition of maternal effects to the later model also provided a satisfactory fit (P = 0.68). However, there were no improvement in the goodness of fit over the simple model, and estimated magnitude of the maternal effect was not significantly different from zero.

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.

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.