Evidence for the genetic control of immunoglobulin E reactivity to the allergens of Alternaria alternata

BACKGROUND: The fungus Alternaria alternata contains potent allergens, and sensitization to these allergens is associated with a high risk of respiratory disease. The influence of genetic regulation on sensitization to Alternaria is unknown. OBJECTIVE: To determine the influence of genetic factors on IgE responses to specific allergens of Alternaria. METHODS: The concordance of skin prick test (SPT), radioallergosorbent test (RAST) and IgE-binding profiles of sera were examined from a large cohort of monozygotic and dizygotic twins. RESULTS: Casewise concordance for a positive SPT response was monozygous (MZ) 66%: dizygous (DZ) 40% (P = 0.002). Logistic regression confirmed that casewise concordance was significantly stronger between MZ than DZ pairs. Immunoblotting against an Alternaria extract revealed 19 allergenic bands. The differences in concordance between the different bands were not significant for either the MZ (P = 0.97) or DZ (P = 0.84) groups. The pooled MZ : DZ difference in concordance was just significant (P = 0.049), suggesting an overall genetic effect on the response to Alternaria. This was reinforced by the comparison of the MZ and DZ correlations for total number of bands recognized (MZ r = 0.65; DZ r = 0.37, P = 0.015). Overall, there was a moderate correlation between the individual SPT weal size and RAST score (r(2) = 0.41) and a substantial correlation between the number of immunoblotted bands and RAST scores (r(2) = 0.79). CONCLUSION: There is a strong genetic influence on IgE response to the mixture of Alternaria allergens and a lesser effect on IgE response to individual allergens.     

Suicidal behavior in twins: a replication

OBJECTIVE: Our two previous reports showed that monozygotic (MZ) twins were significantly more concordant for both completed suicide and attempted suicide than dizygotic (DZ) twins. We wished to replicate the finding that MZ co-twins showed greater concordance for suicidal behavior. METHOD: We collected a new series of 28 twin pairs in which one twin had committed suicide. RESULTS: We found that 4 of the 13 MZ twin pairs were concordant for suicidal behavior compared with 0 of the 15 DZ twin pairs (P=0.035). CONCLUSIONS: These data confirm our previous reports that MZ co-twins show greater concordance for suicidal behavior than DZ co-twins, consistent with genetic influence.     

Genetic and environmental influences on birthweight in a sample of Korean twins

This study is the first report of genetic and environmental influences on birthweight using Korean twins. The sample consisted of 255 monozygotic (MZ) and 178 dizygotic (DZ) twin pairs drawn from the Seoul Twin Family Study. Intraclass twin correlations were computed for the twins' birthweights obtained from parents (typically mothers) of the twins. To estimate genetic and shared and nonshared environmental influences on birthweight, standard univariate model-fitting analyses were performed using a software, Mx. For each gender, MZ twin correlations were higher than DZ twin correlations, suggesting existence of genetic influences on birthweight; however, DZ twin correlations were higher than half the MZ twin correlations, indicating that shared environmental factors are also important. For each zygosity, twin correlations were not significantly different between males and females, implicating that genes and environments that cause individual differences in birthweight may not vary between males and females. Model-fitting analyses based on the data pooled across gender yielded estimates of 17% for genetic, 60% for shared environmental, and 23% for nonshared environmental influences on birthweight.     

Neuropathologic Assessment of Dementia Markers in Identical and Fraternal Twins

Twin studies are an incomparable source of investigation to shed light on genetic and non‐genetic components of neurodegenerative diseases, as Alzheimer's disease (AD). Detailed clinicopathologic correlations using twin longitudinal data and post‐mortem examinations are mostly missing. We describe clinical and pathologic findings of seven monozygotic (MZ) and dizygotic (DZ) twin pairs. Our findings show good agreement between clinical and pathologic diagnoses in the majority of the twin pairs, with greater neuropathologic concordance in MZ than DZ twins. Greater neuropathologic concordance was found for β‐amyloid than tau pathology within the pairs. ApoE4 was associated with higher β‐amyloid and earlier dementia onset, and importantly, higher frequency of other co‐occurring brain pathologies, regardless of the zygosity. Dementia onset, dementia duration, difference between twins in age at dementia onset and at death, did not correlate with AD pathology. These clinicopathologic correlations of older identical and fraternal twins support the relevance of genetic factors in AD, but not their sufficiency to determine the pathology, and consequently the disease, even in monozygotic twins. It is the interaction among genetic and non‐genetic risks which plays a major role in influencing, or probably determining, the degeneration of those brain circuits associated with pathology and cognitive deficits in AD.     

Twin study of genetic and aging effects on X chromosome inactivation

To investigate the genetic influence on X chromosome inactivation and on age-related skewing of X inactivation, in particular, we analysed the X inactivation pattern (XIP) in peripheral blood cells from 118 young monozygotic (MZ) twin pairs (18-53 years), 82 elderly MZ twin pairs (55-94 years), 146 young dizygotic (DZ) twin pairs (20-54 years) and 112 elderly DZ twin pairs (64-95 years). Elderly twins had a higher frequency of skewed X inactivation (34%) than young twins (15%) (P<0.001). Our data suggest that the increase in skewing occurs after age 50-60 years. The intraclass correlation was 0.61 and 0.58 in young and elderly MZ twin pairs, and 0.08 and 0.09 in young and elderly DZ twin pairs. Biometric analysis showed that dominant genetic effects accounted for 63 and 58% of the variance of XIP in the young and elderly twin pairs, respectively. The dominant genetic effect and the shared environment for monochorionic MZ twins may explain the high intraclass correlation for the MZ twin pairs compared to the DZ twin pairs. We did not observe a significant decrease in the intraclass correlation in elderly MZ twins compared to young MZ twins, which would be expected if age-related skewing were due to stochastic factors. We conclude that the increased skewing with age implies that a genetically dependent selection of blood cells take place.     

Fetal alcohol syndrome in twins of alcoholic mothers: Concordance of diagnosis and IQ

The effects of teratogens can be modified by genetic differences in fetal susceptibility and resistance. Twins of alcoholic mothers provide a unique opportunity to study this phenomenon with respect to alcohol teratogenesis. Sixteen pairs of twins, 5 MZ and 11 DZ, all heavily exposed to alcohol prenatally, were evaluated. They represented all available twins of alcohol-abusing mothers who were on the patient rolls of the authors. The rate of concordance for diagnosis was 5/5 for MZ and 7/11 for DZ twins. In two DZ pairs, one twin had fetal alcohol syndrome (FAS), while the other had fetal alcohol effects (FAE). In 2 other DZ pairs, one twin had no diagnosis while one had FAE. IQ scores were most similar within pairs of MZ twins and least similar within pairs of DZ twins discordant for diagnosis. Despite equivalent alcohol exposure within twin pairs, alcohol teratogenesis appears to be more uniformly expressed in MZ than in DZ twins. These data are interpreted as reflecting the modulating influence of genes in the expression of the teratogenic effects of alcohol. © 1993 Wiley-Liss, Inc.     

Multivariate path analysis of cognitive ability measures in reading-disabled and control nuclear families and twins

Matrix notation is used to formulate a multivariate path model of familial resemblance in nuclear families, monozygotic (MZ) twin pairs, and dizygotic (DZ) twin pairs. The model incorporates multivariate genetic and environmental influences, cultural transmission, assortative mating, and environmental influences shared by offspring, and it permits the estimation of genetic and environmental correlations. The model is applied to data from nuclear families, MZ twin pairs, and DZ twin pairs in which at least one child was diagnosed as being reading disabled and to data from control families and twins. Three cognitive ability measures (Reading, Coding Speed, and Spatial Ability) were analyzed simultaneously. Results indicate that genetic influences are moderate, with significant genetic correlations among characters. Cultural transmission is negligible, as are the environmental correlations. Assortative mating is significant only for the Reading measure. There is no evidence for sibling shared environmental influences; however, there are significant twin shared environmental effects for each measure but not between measures.This work was supported by grants from the Spencer Foundation and the NICHD (HD-11681) to J. C. DeFries and by NIMH Postdoctoral Training Grant MH-17104.     

Genetic and Environmental Factors in Relative Body Weight and Human Adiposity

We review the literature on the familial resemblance of body mass index (BMI) and other adiposity measures and find strikingly convergent results for a variety of relationships. Results from twin studies suggest that genetic factors explain 50 to 90% of the variance in BMI. Family studies generally report estimates of parent–offspring and sibling correlations in agreement with heritabilities of 20 to 80%. Data from adoption studies are consistent with genetic factors accounting for 20 to 60% of the variation in BMI. Based on data from more than 25,000 twin pairs and 50,000 biological and adoptive family members, the weighted mean correlations are .74 for MZ twins, .32 for DZ twins, .25 for siblings, .19 for parent–offspring pairs, .06 for adoptive relatives, and .12 for spouses. Advantages and disadvantages of twin, family, and adoption studies are reviewed. Data from the Virginia 30,000, including twins and their parents, siblings, spouses, and children, were analyzed using a structural equation model (Stealth) which estimates additive and dominance genetic variance, cultural transmission, assortative mating, nonparental shared environment, and special twin and MZ twin environmental variance. Genetic factors explained 67% of the variance in males and females, of which half is due to dominance. A small proportion of the genetic variance was attributed to the consequences of assortative mating. The remainder of the variance is accounted for by unique environmental factors, of which 7% is correlated across twins. No evidence was found for a special MZ twin environment, thereby supporting the equal environment assumption. These results are consistent with other studies in suggesting that genetic factors play a significant role in the causes of individual differences in relative body weight and human adiposity.     

Dermatoglyphic total patterns on palms, finger-tips and soles in twins

110 palms of MZ twins and 111 like-sexed pairs of DZ twins have been compared in respect of a concordance rate of the palmar, sole and finger-tip total pattern types. Dermatoglyphic patterns have been classified according to the topological method, and the distributions of the numbers of discordant pattern elements from homolateral, heterolateral and bilateral comparisons in MZ and DZ twins, respectively, are presented. The highest concordance occurs in homolateral comparisons in MZ twins and the lowest in heterolateral comparisons. Bilateral concordance is highest for sole and finger-patterns, while palmar patterns present a considerable degree of dermatoglyphic asymmetry. Palmar, sole and finger-tip patterns are also not alike in homolateral concordance rates within MZ and DZ twin pairs. The differences between MZ and DZ twins are much more pronounced for sole patterns than for palmar or finger-tip patterns, which is also reflected in the estimated H values. For soles, this may be in some way related to the considerable symmetry of patterns. The fact that some pattern elements are intercorrelated may also introduce a bias in estimates of heritability, based on twin material.     

Dermatoglyphic total patterns on palms,finger-tips and soles in twins

110 palms of MZ twins and 111 like-sexed pairs of DZ twins have been compared in respect of a concordance rate of the palmar, sole and finger-tip total pattern types. Dermatoglyphic patterns have been classified according to the topological method, and the distributions of the numbers of discordant pattern elements from homolateral, heterolateral and bilateral comparisons in MZ and DZ twins, respectively, are presented.

The highest concordance occurs in homolateral comparisons in MZ twins and the lowest in heterolateral comparisons. Bilateral concordance is highest for sole and finger-patterns, while palmar patterns present a considerable degree of dermatoglyphic asymmetry.

Palmar, sole and finger-tip patterns are also not alike in homolateral concordance rates within MZ and DZ twin pairs. The differences between MZ and DZ twins are much more pronounced for sole patterns than for palmar or finger-tip patterns, which is also reflected in the estimated H values. For soles, this may be in some way related to the considerable symmetry of patterns. The fact that some pattern elements are intercorrelated may also introduce a bias in estimates of heritability, based on twin material.     

Cord blood immunoglobulin E in like-sexed monozygotic and dizygotic twins

Genetic and environmental factors have been implicated in the etiology of atopy and of serum IgE levels. In order to eliminate post-natal environmental influences we measured IgE in cord blood (CB-IgE) from a cohort of unselected, like-sexed twins. IgE determination was performed with a sensitive radioimmunoassay with a detection limit of 0.01 kU/l. Samples with contamination by maternal blood were identified by IgA determination and excluded. CB-IgE was evaluated in 29 monozygotic (MZ) and 28 dizygotic (DZ) twin pairs. The means and variances for IgE values were comparable for MZ and DZ twins when sex was controlled for. Placental anatomy (MZ twins with mono-and dichorial placenta and DZ twins with one or two placentae) had no significant influence on the IgE levels. In an analysis of variance with subsampling the among-pair, within-pair and analytical variance components were calculated. The analytical variance was well below the biological variances. Biometrical analysis showed that the best model by Akaike Information Criteria was a model including only additive genetic and non-shared environmental factors. With this model the heritability estimate was 0.8. These data suggest that the majority of the variation in CB-IgE is accounted for by genetic factors, but a substantial effect of a common environment cannot be excluded with the present sample size.     

Heritability and risk factors of uterine fibroids--the Finnish Twin Cohort study

OBJECTIVES: Our aim was to study heritability, risk factors and hospitalization for uterine fibroids. METHODS: A random sample of 80 MZ and 80 DZ twins from the Finnish Twin Cohort were invited and 51% of the eligible women (n=82, 17 MZ and 16 DZ pairs, 40-47 years, mean age 43.0), underwent a transvaginal ultrasound. The entire cohort of 13872 women was linked to the national hospital discharge registry 1972-1990. RESULTS: Prevalence of fibroids was 66% and the average number of fibroids 1.7. The casewise concordance for being hospitalized for uterine fibroids was higher in MZ (0.31, 95% CI 0.24-0.37) than in DZ pairs (0.18, 95% CI 0.14-0.22). The proportion of variance in liability to fibroid hospitalization accounted for by genetic factors was 54.8% (95% CI 46.2-62.7%). Women with fibroids had higher body mass index (23.7 vs 21.7, P=0.0086), lower age at first birth (25.7 vs 29.3, P=0.012) and higher parity (3+ children 48.2 vs 29.6%, P=0.009) than women without fibroids. Risk ratio (RR) for fibroids in a MZ twin whose sister had been diagnosed with fibroids was 1.1 (95% CI 0.08;15), for a DZ twin 1.1 (95% CI 0.16;8.8) and for all twins 1.3 (95% CI 0.3; 6.1). Intraclass correlation for the number of fibroids was 0.24 for MZ and 0.11 for DZ twins, yielding an heritability estimate of 0.26. CONCLUSION: Reproductive and anthropometric factors may have at least as large role in pathogenesis of fibroids than genetic factors.     

Time course of onset of sensitization to common and occupational inhalants in apprentices

BACKGROUND: Incident sensitization to common allergens in the setting of sensitization to an occupational allergen has not been described. OBJECTIVE: Our aim was to determine the risk and timing of development of sensitization to common allergens in subjects with incident sensitization to a work-related allergen. METHODS: Data from a cohort of 769 apprentices in animal-health technology, pastry making, and dental hygiene were used. Skin prick tests to work-related allergens (laboratory animal, flour, and latex) and common allergens (mites, molds, pets, and pollen) were administered at baseline and at up to 3 subsequent annual visits. Risk ratios (RRs) and 95% CIs were calculated. RESULTS: Eighty-three subjects had sensitization to a work-related allergen. Four (4.8%) subjects became sensitized to common and then occupational allergens. Nine (10.8%) subjects had sensitization to a common allergen after sensitization to a work-related allergen. In 20 (24.1%) subjects new sensitizations to specific and common allergens were detected simultaneously. Fifty subjects remained free from new sensitization to occupational allergen during development of sensitization to common allergens. An increased risk of development of sensitization to molds (RR = 3.49) and pets (RR = 2.51) was found in subjects with incident sensitization to occupational allergens relative to the risk in subjects without sensitization. CONCLUSION: New sensitization to common aeroallergens is frequent in subjects not previously exposed to work-related allergens; it often occurs around the same time as sensitization to work-related agents. Subjects with new occupational sensitization are at a greater risk of development of sensitization to common aeroallergens than subjects without sensitization.     

Hay fever – a Finnish nationwide study of adolescent twins and their parents

Background Like other atopic diseases, hay fever is known to cluster in families. This clustering is due either to effects of a shared family environment or to genetic inheritance. By comparing the occurrence of hay fever among monozygous (MZ) and dizygous (DZ) twin pairs, we were able t o estimate the contribution of genetic and environmental factors in the development of hay fever.
Methods A questionnaire mailed to a nationwide sample of 2483 families with 16-year-old twins furnished data for the cumulative incidence of physician-diagnosed hay fever among these adolescents and their parents. Results Among the 1765 twin pairs with data available for analysis, hay fever was reported for 14.1% of boys (95% CI = 12.4-15.8%) and 10.0% of girls (95% CI=8.6-11.4%). The MZ twin pairs (probandwise concordance rate=60.3%, 95% CI=52-68%) were significantly more concordant for hay fever than were DZ twin pairs (31.5%, 95% Cl=26-36%). Genetic factors accounted for 74-82% of the interindividual variability in liability to hay fever, variation in shared family environment for 7% at most, and unique (individual) environment for 18%.
Conclusions Familial occurrence of hay fever is mainly due to genes predisposing to the trait. Environmental exposures shared in common by family members but varying between families appear to account for at most a modest proportion of the variability in risk of developing hay fever.     

Birch pollen sensitization with cross‐reactivity to food allergens predominates in adults with eosinophilic esophagitis

EoE patients show variable sensitization patterns to food and aeroallergens. The value of allergy testing in adult EoE patients is unclear. Component‐resolved diagnosis (CRD) may offer additional insights into sensitization patterns. The aim of this study was to characterize sensitization patterns in adult EoE patients using CRD. Serum from 76 patients (17 female), age 38.6 ± 1.5 years, was analyzed for reactivity to 112 different allergen components using an immuno‐solid‐phase allergen chip (ISAC). We observed any sensitization in 59 patients (78%), of which 54 patients were polysensitized. Aeroallergen sensitization, mostly against components of grass or tree pollen, or house dust mite, was observed in 74% of the patients. Birch pollen (rBet v 1) sensitization with cross‐reactivity to food allergen components was observed in 30 patients (39%). In conclusion, food sensitizations in EoE patients are mainly caused by cross‐reactivity to food allergens after primary birch pollen sensitization. Pollen and food sensitizations may cause or maintain esophageal inflammation in EoE patients. CRD provides more insight into sensitization patterns, identifies additional food allergen sensitizations and might be useful to direct dietary therapy in EoE.     

Intrapair similarity in frequency of disfluency in monozygotic and dizygotic twin pairs containing stutterers

It is known that concordance for stuttering is higher in monozygotic (MZ) than in dizygotic (DZ) twins. Evidence for genetic contribution to the frequency of speech disruption in stutterers was examined in 17 pairs of MZ and 13 pairs of DZ twins, each pair containing at least one stutterer. Intraclass correlations and analyses of variance indicated positive evidence for a genetic contribution to the overall frequency of disfluency in speech and to the frequency of certain types of speech disruption (blocked and prolonged sounds). There was little evidence for genetic influence on other types of speech disruption (various types of repetitions and interjections) In those disfluency types for which genetic predictions were confirmed, evidence of excessive dissimilarity in DZ cotwins suggests that a simple, additive gene-environment model is unlikely to be appropriate for disfluency frequency data.     

Chromosome findings in twins with early-onset autistic disorder

In a twin study of autistic disorder, chromosome analyses were carried out in nine pairs of monozygotic (MZ) twins, two pairs of dizygotic (DZ) twins, one set of MZ triplets, one single twin from a MZ pair, and seven single twins from DZ pairs. All but one of the MZ sets were concordant for autistic disorder; all DZ pairs were discordant. Fragile X(q)(27.3) was found in one pair of MZ twins and in MZ triplets, i.e., in 9% of the population with autistic disorder. A marker chromosome of unknown origin was detected in a male twin with autistic disorder from a discordant DZ pair.     

Heritability of food preferences in young children

BACKGROUND: There is persisting interest in the idea that taste preferences are heritable characteristics, but few twin studies have found evidence for a significant genetic component. Small sample sizes and idiosyncratic selection of foods may have contributed to the negative results. We hypothesized that using a larger twin sample and empirical groupings of food types, would give stronger evidence for the heritability of food preferences. OBJECTIVE: We examined the heritability of preferences for four food groups in a sample of young twins. DESIGN: We administered a food preference questionnaire with 95 foods to 214 mothers of same-sex twin pairs (103 monozygotic and 111 dizygotic pairs) aged 4 to 5. 18 foods were excluded because they had been tried by fewer than 25% of the children. Foods were grouped into 'Vegetables', 'Fruits', 'Desserts' and 'Meat and Fish' on the basis of a factor analysis of the preference data. Genetic analyses were carried out on mean liking across these four groups, using model fitting techniques. RESULTS: Over all 77 foods, MZ correlations were higher than DZ correlations for 72 of them, with a higher mean MZ correlation (r = 0.76) than DZ correlation (r = 0.56). Using model fitting techniques with the factor scores, significant heritability estimates were obtained for all four food groups. Heritability was modest for dessert foods (0.20), moderate for vegetables (0.37) and fruits (0.51), and high for liking for protein foods (0.78). Shared environmental effects were strong for desserts, fruits and vegetables, while non-shared environmental influences were low for all four food groups. CONCLUSIONS: These results provide strong evidence for modest heritability of food preferences when using empirically-derived groupings of foods.