Genetic analysis of febrile convulsions: twin and family studies

Summary Thirty-two twin pairs and 673 sibship-cases with febrile convulsions (FC) were studied. Twin study: (1) The pairwise concordance rate for FC was 56% (10/18 pairs) in monozygotic and 14% (2/14 pairs) in dizygotic twins (P<0.05). (2) Intra-pair similarity of clinical symptoms in concordant twin pairs was greater than that in sibship-cases. Sibship-pair study (population): (3) In sibship-pair study a large positive correlation of some clinical symptoms — in particular, age at onset of FC, exogenous factors, and degree of fever (P<0.001 for each) — was indicated. (4) Compared with FC children with no family history, those with such family history had a higher frequency of age at onset between 8 and 19 months, exogenous factors, low degree of fever before onset of convulsions, many recurrences, and recurrence after age 3 (P<0.01–0.001 for each). (5) Morbidity risk among near relatives was highest in first-degree relatives (16%) than in second (4.0%) or third-degree relatives (4.1%). The following differences were found: siblings (24%)>parents (12%), uncles (4.5%)>aunts (3.5%), male cousins (4.4%)>female cousins (3.8%). Segregation ratio, influence by affection of father or mother, and maternal preponderance were analysed. (6) Similar findings were also observed in the clinic study. (7) A multifactorial mode of inheritance for FC receives some support from this study, and the heritability was estimated to be 75% in the population study. The results may be useful for genetic counselling for FC.     

The frequency of middle phalangeal hair in Saudi Arabia.

Middle phalangeal hair was found to be present in 71% if Saudi Arabian males. For those exhibiting this trait, the frequency of combinations of digits with hair was similar to the frequency in other populations.     

Dermatoglyphic configurations of proximal and middle phalanges in Spaniards

In this paper the dermatoglyphic configurations of proximal and middle phalanges in Spaniards have been analysed. From the data of 112 males and 135 females it is seen that on proximal phalanges the highest frequencies correspond to basic types and enclosures. On the contrary, the middle phalanges are displaying an enlarged frequency distribution. On both phalanges no significant sexual and bimanual differences were found. The hitherto reported population data do not permit to claim clear differences among the main racial groups.     

Classical twin studies and beyond

Twin studies have been a valuable source of information about the genetic basis of complex traits. To maximize the potential of twin studies, large, worldwide registers of data on twins and their relatives have been established. Here, we provide an overview of the current resources for twin research. These can be used to obtain insights into the genetic epidemiology of complex traits and diseases, to study the interaction of genotype with sex, age and lifestyle factors, and to study the causes of co-morbidity between traits and diseases. Because of their design, these registers offer unique opportunities for selected sampling for quantitative trait loci linkage and association studies.     

A note on the distribution of middle phalangeal hair among Tibetans

In the present paper the frequencies of individuals without middle phalangeal hair was found as 55.75% in the Tibetan males and 68.61% in females. Sex differences were noticed in the present sample. Populations of Mongoloid affinity seems to have a marked increase in the frequency of individuals without phalangeal hair and the present Tibetan sample reflects this tendency.     

Distribution of middle phalangeal hair in a population of the south of Spain

In this paper the presence or absence of middle phalangeal hair has been studied in an Andalusian population sample. This sample consists of 245 students from Granada (128 males and 117 females). The frequencies of middle phalangeal hair are similar to those obtained in the Basque population, which show the lowest frequencies so far reported. In our sample no significant sexual or bimanual differences are seen. The most affected finger is the ring-finger, the least affected one is the forefinger. The phenotypes were classified according to the nomenclatures given by Valls and Bernstein.     

Multivariate analysis of craniofacial measurements in twin and family data

Thirty-three cephalometric variables and height have been measured on each of 630 individuals (316 male and 314 female) from 157 families. After age and sex differences were adjusted for each measurement, a rotated factor analysis was undertaken to account for the variation by a limited number of linear combinations of the adjusted measurements. It was found that most of the variation could be explained by nine independent factors. Finally, correlation coefficients were computed on twins, siblings and parent-offspring data for factor scores. The results suggest that each factor which is measured by a linear combination of a set of variables could result from the interaction of independent sets of genes with the environment.     

Inheritance of total serum IgE (basal levels) in man.

Since allergic individuals with atopic allergy tend to have higher total serum IgE levels than do nonallergic subjects, family studies of total serum IgE levels are necessary in delineating the genetic and environmental factors involved in the expression of allergic disease. However, previous studies do not agree as to the genetic basis of total IgE production. To try to resolve this conflict, a total of 278 individuals from 42 nuclear families ascertained for large family size (at least four children) were studied. The families were not selected for the presence of allergic disease. Segregation analysis showed that the mixed model of recessive inheritance of high levels was most appropriate for these data--with approximately 36% of the total phenotypic variation in log[IgE] attributable to genetic factors, equally divided between a Mendelian component and a more general polygenic component. Thus, these data suggest some role for Mendelian control of basal IgE levels, but there is significant familial aggregation in IgE levels over and above that due to a Mendelian factor.     

Netherlands twin family study of anxious depression (NETSAD).

In a longitudinal study of Dutch adolescent and young adult twins, their parents and their siblings, questionnaire data were collected on depression, anxiety and correlated personality traits, such as neuroticism. Data were collected by mailed surveys in 1991, 1993, 1995 and 1997. A total of 13,717 individuals from 3344 families were included in the study. To localise quantitative trait loci (QTLs) involved in anxiety and depression, the survey data were used to select the most informative families for a genome-wide search. For each individual a genetic factor score was computed, based on a genetic multivariate analysis of anxiety, depression, neuroticism and somatic anxiety. A family was selected if at least two siblings (or DZ twins) had extreme factor scores. Both discordant (high-low) and concordant (high-high and low-low) pairs were included in the selected sample. Once an extreme sibling pair was selected, all family members (parents and additional siblings of the selected pair) who had at least once returned a questionnaire booklet were asked to provide a DNA sample. In total, 2724 individuals from 563 families (1007 parents and 1717 offspring) were approached and 1975 individuals from 479 families (643 patients and 1332 offspring) complied by returning a buccal swab for DNA isolation. All offspring from selected families were asked to participate in a psychiatric interview and in a 24-hour ambulatory assessment of cardiovascular parameters and cortisol. The interview consisted of the WHO-Composite International Diagnostic Interview and was administered to 1253 offspring. In this paper we describe the genetic-epidemiological analyses of the survey data on anxiety, somatic anxiety, neuroticism and depression. We detail how these data were used to select families for the QTL study and discuss strategies that may help elucidate the molecular pathways leading from genes to anxious depression.     

Inheritance of heart rate variability: the kibbutzim family study

Heart rate variability (HRV) measures are associated with coronary heart disease incidence and mortality. Therefore insight into the genetic and environmental determinants of these measures may have clinical relevance. We assessed the role of genetic and environmental factors of time domain and frequency domain HRV indices. Participants were 451 kibbutz members, aged 15 and up, belonging to 80 families. HRV indices were calculated from Holter recordings measured over 5 min. Our data indicate that for the two time- and four frequency domain indices, a mixture of two normal distributions fit the data significantly better than a single normal distribution (P<0.05). We used complex segregation analysis to infer the modes of inheritance of these HRV measures. We found evidence for possible involvement of a recessive major gene in the inheritance of the root mean square of successive differences in RR intervals (RMSSD), which is predominantly vagally mediated. A putative major gene explains 28%-34% of the adjusted inter-individual variability. The SD, determined by a mixture of mechanisms, is influenced by environmental and polygenic effects, but not by a major gene. The findings regarding the heritability of the frequency domain indices were not conclusive. However, the involvement of genetic factors was not rejected. Additional studies in extended families are needed to confirm the involvement of major genes in the determination of the autonomic activity.