Monozygous Research Articles

Back Pain without Disease or Substantial Injury in Children and Adolescents: A Twin Family Study Investigating Genetic Influence and Associations.

This twin family study first aimed to investigate the evidence for genetic factors predicting the risk of lifetime prevalence of non-specific low back pain of at least three months duration (LBP (life)) and one-month current prevalence of thoracolumbar back pain (TLBP (current)) using a study of children, adolescents, and their first-degree relatives. Secondly, the study aimed to identify associations between pain in the back with pain in other regions and also with other conditions of interest. Randomly selected families (n = 2479) with child or adolescent twin pairs and their biological parents and first siblings were approached by Twins Research Australia. There were 651 complete twin pairs aged 6-20 years (response 26%). Casewise concordance, correlation, and odds ratios were compared for monozygous (MZ) and dizygous (DZ) pairs to enable inference about the potential existence of genetic vulnerability. Multivariable random effects logistic regression was used to estimate associations between LBP (life) or TLBP (current) as an outcome with the potentially relevant condition as predictors. The MZ pairs were more similar than the DZ pairs for each of the back pain conditions (all p values < 0.02). Both back pain conditions were associated with pain in multiple sites and with primary pain and other conditions using the combined twin and sibling sample (n = 1382). Data were consistent with the existence of genetic influences on the pain measures under the equal environments assumption of the classic twin model and associations with both categories of back pain were consistent with primary pain conditions and syndromes of childhood and adolescence which has research and clinical implications.

Primary dysmenorrhoea in adolescents and young women: A twin family study of maternal transmission, genetic influence and associations.

The extent to which maternal transmission of primary dysmenorrhoea is genetically determined in adolescents and young women has yet to be determined. We aimed to assess heritability and associations relevant to primary pain syndromes using a twin family study. Participants were young menstruating female twins, and their oldest sisters and mothers, whose families were registered with Twins Research Australia and previously participated in a twin family study of primary paediatric pain disorders. Questionnaire packs were mailed, assessing current maximum and average menstrual pain intensity, current pain interference with activities and retrospective dysmenorrhea secondary symptoms. The sample comprised 206 twin individuals (57 monozygous (MZ) and 46 dizygous (DZ) pairs) aged 10-22 years, eldest siblings (n=38) aged 13-28 years and mothers (n=101) aged 32-61 years. The estimated regression coefficient of the relationship between mother-daughter and twin-sibling dyads indicated significant associations for the measures of dysmenorrhea and supported heritability. Adjusted for age, the within twin-pair correlation for MZ twins was generally more than twice that of DZ twins. Heritability estimates were maximal pain intensity 0.67 (P=3.8 × 10-11 ), average pain intensity 0.63 (P=3.7 × 10-10 ), pain interference 0.57 (P=1.8 × 10-8 ) and retrospective symptoms 0.57 (P=1.8 × 10-8 ). Twin individuals with a lifetime (three-month) history of iron deficiency and those with painless restless legs syndrome (RLS) were significantly more likely to have more intense pain associated with menstruation. Primary dysmenorrhea in adolescents and young women was shown to be relatively strongly genetically influenced and associated especially with a history of iron deficiency and painless RLS which have potential therapeutic implications.

Familial and Genetic Influences on the Common Pediatric Primary Pain Disorders: A Twin Family Study.

The primary pain disorders of childhood are highly prevalent but have infrequently been studied collectively. Genetic influences have been suggested to be causally implicated. Surveys were sent to 3909 Australian twin families, assessing the lifetime prevalence of growing pains, migraine, headache, recurrent abdominal pain, low back pain, and persistent pain (not otherwise specified) in pediatric twins and their immediate family members. Comparisons between monozygous (MZ) and dizygous (DZ) twin pair correlations, concordances and odds ratios were performed to assess the contribution of additive genetic influences. Random-effects logistic regression modelling was used to evaluate relationships between twin individuals and their co-twins, mothers, fathers and oldest siblings with the subject conditions. Twin analyses of responses from 1016 families revealed significant influence of additive genetic effects on the presence of growing pains, migraine, and recurrent abdominal pain. The analyses for headache, low back pain, and persistent pain overall did not conclusively demonstrate that genetic influences were implicated more than shared environmental factors. Regression analyses demonstrated varying levels of significance in relationships between family members and twin individuals for the tested conditions, with strongest support for genetic influences in growing pains and migraine. These data, together with previously published association analyses, suggest common causal influences including genes.

Contrasting painless and painful phenotypes of pediatric restless legs syndrome: a twin family study

ObjectiveThis study was designed to investigate painless and painful subsets of pediatric restless legs syndrome (RLS) for genetic influence and for associations with iron deficiency and common pediatric pain disorders. MethodsIn a twin family study, twins (3–18 years) and their oldest siblings, mothers and fathers completed questionnaires, assessing lifetime prevalence of RLS using current criteria, as well as history of iron deficiency and pediatric pain disorders. Subsets were categorized as RLS-Painless or RLS-Painful. Within twin pair analyses were conducted to assess familial and potential genetic effects for the defined subsets. Penalized maximum likelihood logistic regression was used to test familial associations. Random-effects logistic regression modeling was used in the total pediatric sample to investigate univariate and multivariate associations with the subsets. ResultsData were available for 2033 twin individuals (1007 monozygous (MZ), 1026 dizygous (DZ); 51.7% female), 688 siblings, 1013 mothers and 921 fathers. Odds ratios, correlations and casewise concordance were significantly higher in MZ than in DZ twins only for RLS-Painful. RLS-Painless, though familial (co-twin and mother), was not genetically influenced, but was independently associated with female sex (OR 0.52, p = 0.003), iron deficiency (OR 4.20, p < 0.001) and with persistent pain disorders (OR 2.28, p = 0.02). RLS-Painful was familial and was probably genetically influenced; was independently associated with non-migraine headaches (OR 2.70, p = 0.02) and recurrent abdominal pain (OR 2.07, p = 0.04). ConclusionsPediatric RLS was heterogeneous and was categorized into contrasting painless and painful phenotypes. RLS-Painless was associated with iron deficiency while RLS-Painful accounted for the heritability of RLS.

Skeletal Muscle Gene Expression Study of Monozygous Twins with 35 Years of Divergent Exercise History

Variations in physical ability and capacities among individuals depend on both genetic inheritance and lifestyle. Previous research has yet to utilize a human model of monozygous (MZ) twins with substantial and long-term differences in exercise backgrounds to identify molecular and cellular mechanisms underlying exercise-mediated adaptations in muscle and whole-body phenotype. PURPOSE: In particular, this study examined skeletal muscle expression of genes related to muscle growth, inflammation, metabolism, and fiber type distribution in MZ twins with 35 years of substantially differing exercise history. METHODS: Muscle biopsies were collected from the vastus lateralis of male, 52-year-old MZ twins. Reverse transcriptase-polymerase chain reaction was used for the quantification of mRNAs associated with the following gene markers of various adaptive responses: a) skeletal muscle fiber type shift: MyHC-1, MyHC-2a, and MyHC-2x; b) adaptations in oxidative capacity: transcription factor A of the mitochondria (TFAM), and citrate synthase; c) angiogenesis: endothelial nitric oxide synthase, and vascular endothelial growth factor; d) muscular growth and satellite cell activation: myostatin, Pax7 (PAX7), mechano-growth factor (IGF1Ec), insulin-like growth factor a (IGF1Ea), and MyoD; and e) the inflammatory response: TWEAK (TNFSF12), the FN14 TWEAK receptor (TNFRSF12A) and tumor necrosis factor-α (TNF). RESULTS: MyHC-2x was expressed at a lower level in the trained subject relative to the untrained subject. No differences were observed for other markers of fiber type or metabolic or angiogenesis gene products. Some differences were observed in the expression of genes related to muscle growth including elevations in PAX7, MGF and IGF1Ea, and a reduction in MyoD. Finally, the only difference in expression of markers for the inflammatory response was an elevation in TNFRSF12A in the trained twin. CONCLUSIONS: At the mRNA-level, differences in expression of some key markers related to muscle fiber type, muscle growth, and the inflammatory response were observed in the trained vs the untrained twin. These data highlight the adaptability of skeletal muscle at the molecular level with decades of divergent physical activity patterns.

VATER/VACTERL association

The VATER/VACTERL association is typically defined by the presence of at least three of the following congenital malformations: vertebral anomalies, anal atresia, cardiac malformations, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. The identification of 14 twin pairs with an initial diagnosis of VATER/VACTERL association at our clinical centers led to the performance of a classical twin study. This involved a thorough evaluation of these 14 twin pairs and a further 55 twin pairs identified from a systematic review of the literature. The zygosity, concordance, and malformation status of all 69 twin pairs were evaluated. Twenty-four twin pairs fulfilled the criteria for inclusion in a comparison of the concordance rates between monozygous (MZ) and dizygous (DZ) twin pairs. The pairwise concordance rates were 15% [95% confidence interval (CI) 4-42%] for MZ and 18% (95% CI 5-48%) for DZ twin pairs (P=0.53). The probandwise concordance rates were 27% (95% CI 11-52%) for MZ and 31% (95% CI 13-58%) for DZ twin pairs (P=0.40). Although based on a limited number of twin pairs, the findings of the present study are consistent with the low number of familial cases reported to date, and suggest that the role of inherited genetic factors in the majority of VATER/VACTERL cases is limited.

Heritability of Respiratory Infection with Pseudomonas aeruginosa in Cystic Fibrosis

To quantify the relative contribution of factors other than cystic fibrosis transmembrane conductance regulator genotype and environment on the acquisition of Pseudomonas aeruginosa (Pa) by patients with cystic fibrosis. Lung infection with Pa and mucoid Pa was assessed using a co-twin study design of 44 monozygous (MZ) and 17 dizygous (DZ) twin pairs. Two definitions were used to establish infection: first positive culture and persistent positive culture. Genetic contribution to infection (ie, heritability) was estimated based on concordance analysis, logistic regression, and age at onset of infection through comparison of intraclass correlation coefficients. Concordance for persistent Pa infection was higher in MZ (0.83; 25 of 30 pairs) than DZ twins (0.45; 5 of 11 pairs), generating a heritability of 0.76. Logistic regression adjusted for age corroborated genetic control of persistent Pa infection. The correlation for age at persistent Pa infection was higher in MZ twins (0.589; 95% CI, 0.222-0.704) than in DZ twins (0.162; 95% CI, -0.352 to 0.607), generating a heritability of 0.85. Genetic modifiers play a significant role in the establishment and timing of persistent Pa infection in individuals with cystic fibrosis.

Nine new twin pairs with esophageal atresia: A review of the literature and performance of a twin study of the disorder

Isolated esophageal atresia (EA) is a rare congenital malformation whose etiology remains largely unknown. Nine twin pairs with EA were identified from our clinical service, prompting the performance of a systematic review of the literature and the first reported twin study of isolated EA. A total of 330 twin pairs with EA were identified from the literature. The zygosity, concordance, and malformation (isolated vs. nonisolated) status of all 339 twin pairs were evaluated. A total of 72 twin pairs (4 of 9 / 68 of 330) fulfilled the criteria for inclusion in a classic twin study of isolated EA. The pairwise concordance rates were 50% (95% confidence interval [CI], 34-66%) for monozygous (MZ) twin pairs and 26% (95% CI, 15-42%) for dizygous (DZ) twin pairs (p = 0.033). The probandwise concordance rates were 67% (95% CI, 53-78%) for MZ twin pairs and 42% (95% CI, 29-56%) for DZ twin pairs (p = 0.011). The MZ/DZ ratios were 1.9 for pairwise analysis and 1.6 for probandwise analysis. The familial risk ratios for MZ and DZ twin pairs were 1700 and 900, respectively. The observation of higher concordance rates for MZ compared to DZ twin pairs indicates that genetic factors contribute to isolated EA.

Are genetic and environmental components of variance in mammographic density measures that predict breast cancer risk independent of within-twin pair differences in body mass index?

To understand the role of mammographic density on breast cancer risk, it is important to take into account body mass index (BMI). As with age, BMI is negatively confounded with mammographic density, and a previous US twin study found that the covariance structure of mammographic density depended on the extent to which pairs differ in BMI. Using a computerised thresholding technique, we measured mammographic dense area for 571 monozygous (MZ) and 380 dizygous (DZ) twin pairs aged 40-70 years from Australia and North America. After adjusting for age and BMI, we calculated estimates of variance, covariance, correlation and, under the assumptions of the classic twin model, additive genetic (A), common environment (C) and person-specific environmental (E) components of variance. Analyses were conducted both within and across categories of within-pair differences in BMI, under a bivariate normal model using the software FISHER. The variance, MZ and DZ correlations, and the differences between MZ and DZ correlations and covariances were not constant across absolute within-pair differences in BMI (for the DZ correlation, P = 0.04, all other P < 0.001). No model involving a combination of one or more of A, C and E gave an acceptable fit. The interpretation of these observations is not straightforward. They, and other data, challenge the assumptions of the classic twin model for mammographic density and suggest that an insightful test of those assumptions can be made by testing the stability of correlations, covariances and variance components across absolute within-pair differences in potential mediators.

Causes of variation in the frequency of monozygous and dizygous twinning in various breeds of cattle.

A statistical investigation has been made comprising 12 European cattle breeds with a total of about 5.3 milj. calvings and 120,000 twin births. Season of conception has a marked influence on the frequency of twin births, one maximum corresponding to spring and another one to autumn conceptions. There are significant breed differences in the relation between age of the cows, measured in parities, and the frequency of monozygous (MZ) as well as dizygous (DZ) twin births. On an average, the DZ frequency increases more than the MZ frequency from the first to the fourth-fifth calving; then the age-curves show a plateauing tendency. After the first twin birth, the twinning frequency at the following calvings is 4–5 times higher than in the general population. Apparently, twinning depends on polygenic inheritance and also on various environmental influences, with a threshold for the phenotypic manifestation. It may be assumed that the underlying liability of the cows in a population to bear twins has an approximately normal distribution. The heritability of twinning has been estimated on the binomial p-scale as well as on the x-scale of the normal curve. On the p-scale the heritability of twinning was found to be about 0.02 which corresponds to 0.16 on the x-scale, although with some differences between breeds.

Sudden Infant Death Syndrome in Twins and Singletons

Twins compared with singletons and monozygous (MZ) compared with dizygous (DZ) twins are at increased risk of fetal and infant death, cerebral palsy and many congenital anomalies. The aim of this study is to investigate whether zygosity is a risk factor for the sudden infant death syndrome (SIDS). Birth registration data and draft infant death certificates for all multiple births in England and Wales 1993 to 2003 were provided by the Office for National Statistics. As a partial proxy for zygosity, same-sex was compared with opposite-sex twins for birthweight-specific mortality and mortality attributed to SIDS. Data on singleton infants were obtained by subtraction of multiple births from routinely published population births and infant deaths. SIDS mortality among low birthweight infants was significantly less in twins than singletons. The twin-singleton relative risk was reversed in infants of normal birthweight. Among infants of normal birthweight, neonatal SIDS was significantly more common in same- compared with opposite-sex pairs. Among infants of low birthweight, postneonatal SIDS was significantly more common in same- compared with opposite-sex pairs. The difference in birthweight distribution of same- compared with opposite-sex twins for neonatal SIDS suggests that zygosity is a risk factor for SIDS. As congenital cerebral anomalies are a feature of many monozygous twin conceptions, a detailed macro- and microscopical examination of the brain in twin SIDS may indicate an otherwise unrecognised pathology.

Heritability of Lung Disease Severity in Cystic Fibrosis

Obstructive lung disease, the major cause of mortality in cystic fibrosis (CF), is poorly correlated with mutations in the disease-causing gene, indicating that other factors determine severity of lung disease. To quantify the contribution of modifier genes to variation in CF lung disease severity. Pulmonary function data from patients with CF living with their affected twin or sibling were converted into reference values based on both healthy and CF populations. The best measure of FEV(1) within the last year was used for cross-sectional analysis. FEV(1) measures collected over at least 4 years were used for longitudinal analysis. Genetic contribution to disease variation (i.e., heritability) was estimated in two ways: by comparing similarity of lung function in monozygous (MZ) twins (approximately 100% gene sharing) with that of dizygous (DZ) twins/siblings (approximately 50% gene sharing), and by comparing similarity of lung function measures for related siblings to similarity for all study subjects. Forty-seven MZ twin pairs, 10 DZ twin pairs, and 231 sibling pairs (of a total of 526 patients) with CF were studied. Correlations for all measures of lung function for MZ twins (0.82-0.91, p < 0.0001) were higher than for DZ twins and siblings (0.50-0.64, p < 0.001). Heritability estimates from both methods were consistent for each measure of lung function and ranged from 0.54 to 1.0. Heritability estimates generally increased after adjustment for differences in nutritional status (measured as body mass index z-score). Our heritability estimates indicate substantial genetic control of variation in CF lung disease severity, independent of CFTR genotype.

Relative Contribution of Genetic and Nongenetic Modifiers to Intestinal Obstruction in Cystic Fibrosis

Neonatal intestinal obstruction (meconium ileus [MI]) occurs in 15% of patients with cystic fibrosis (CF). Our aim was to determine the relative contribution of genetic and nongenetic modifiers to the development of this major complication of CF. A total of 65 monozygous twin pairs, 23 dizygous twin/triplet sets, and 349 sets of siblings with CF were analyzed for MI status, significant covariates, and genome-wide linkage. Specific mutations in the CF transmembrane conductance regulator (CFTR), the gene responsible for CF, correlated with MI, indicating a role for CFTR genotype. Monozygous twins showed substantially greater concordance for MI than dizygous twins and siblings (P = 1 x 10(-5)), showing that modifier genes independent of CFTR contribute substantially to this trait. Regression analysis revealed that MI was correlated with distal intestinal obstruction syndrome (P = 8 x 10(-4)). Unlike MI, concordance analysis indicated that the risk for development of distal intestinal obstruction syndrome in CF patients is caused primarily by nongenetic factors. Regions of suggestive linkage (logarithm of the odds of linkage >2.0) for modifier genes that cause MI (chromosomes 4q35.1, 8p23.1, and 11q25) or protect from MI (chromosomes 20p11.22 and 21q22.3) were identified by genome-wide analyses. These analyses did not support the existence of a major modifier gene on chromosome 19 in a region previously linked to MI. The CFTR gene along with 2 or more modifier genes are the major determinants of intestinal obstruction in newborn CF patients, whereas intestinal obstruction in older CF patients is caused primarily by nongenetic factors.

Using Bivariate Models to Understand between‐ and within‐Cluster Regression Coefficients, with Application to Twin Data

In the regression analysis of clustered data it is important to allow for the possibility of distinct between- and within-cluster exposure effects on the outcome measure, represented, respectively, by regression coefficients for the cluster mean and the deviation of the individual-level exposure value from this mean. In twin data, the within-pair regression effect represents association conditional on exposures shared within pairs, including any common genetic or environmental influences on the outcome measure. It has therefore been proposed that a comparison of the within-pair regression effects between monozygous (MZ) and dizygous (DZ) twins can be used to examine whether the association between exposure and outcome has a genetic origin. We address this issue by proposing a bivariate model for exposure and outcome measurements in twin-pair data. The between- and within-pair regression coefficients are shown to be weighted averages of ratios of the exposure and outcome variances and covariances, from which it is straightforward to determine the conditions under which the within-pair regression effect in MZ pairs will be different from that in DZ pairs. In particular, we show that a correlation structure in twin pairs for exposure and outcome that appears to be due to genetic factors will not necessarily be reflected in distinct MZ and DZ values for the within-pair regression coefficients. We illustrate these results in a study of female twin pairs from Australia and North America relating mammographic breast density to weight and body mass index.

Verification of Self-Report of Zygosity Determined via DNA Testing in a Subset of the NAS-NRC Twin Registry 40 Years Later

AbstractThe National Academy of Sciences — National Research Council (NAS-NRC) twin panel, created nearly 50 years ago, had twin zygosity determined primarily via a similarity questionnaire that has been estimated to correctly classify at least 95% of twins. In the course of a study on the genetics of healthy ageing in the NAS-NRC twins, DNA was collected for genome-wide scanning and zygosity confirmation was examined in 343 participating pairs. The sample was supplemented from two other studies using NAS-NRC twins where one or both co-twins were suspected to have Alzheimer disease or another dementia, or Parkinson's disease. Overall 578 twin pairs with DNA were analyzed. Zygosity assignment for 96.8% (519/536) was confirmed via questionnaire. Among 42 pairs whose questionnaire responses were inconclusive for assigning zygosity, 50% were found to be monozygous (MZ) and 50% were dizygous (DZ). There was some evidence for greater misclassification of presumed DZ pairs in the healthy ageing study where participation favored pairs who were similar in having a favorable health history and willingness to volunteer without any element of perceived risk for a specific disease influencing participation.

Verification of Self-Report of Zygosity Determined via DNA Testing in a Subset of the NAS-NRC Twin Registry 40 Years Later

The National Academy of Sciences -- National Research Council (NAS-NRC) twin panel, created nearly 50 years ago, had twin zygosity determined primarily via a similarity questionnaire that has been estimated to correctly classify at least 95% of twins. In the course of a study on the genetics of healthy ageing in the NAS-NRC twins, DNA was collected for genome-wide scanning and zygosity confirmation was examined in 343 participating pairs. The sample was supplemented from two other studies using NAS-NRC twins where one or both co-twins were suspected to have Alzheimer disease or another dementia, or Parkinson's disease. Overall 578 twin pairs with DNA were analyzed. Zygosity assignment for 96.8% (519/536) was confirmed via questionnaire. Among 42 pairs whose questionnaire responses were inconclusive for assigning zygosity, 50% were found to be monozygous (MZ) and 50% were dizygous (DZ). There was some evidence for greater misclassification of presumed DZ pairs in the healthy ageing study where participation favored pairs who were similar in having a favorable health history and willingness to volunteer without any element of perceived risk for a specific disease influencing participation.

Genetic contribution to dental arch size variation in Australian twins

The aim of this study was to quantify the relative contributions of genetic and environmental factors to variations in dental arch breadth, length and palatal height in a sample of Australian twins, and to estimate heritabilities using modern model-fitting methods. Dental casts of 20 male and 24 female monozygous (MZ) twin pairs, 17 male and 8 female dizygous (DZ) twin pairs, and 9 opposite-sexed DZ twin pairs were selected from the collection of records of twins housed at the Adelaide Dental School. The mean ages of subjects were 15.8 +/- 3.5 years (MZ) and 17.0 +/- 4.7 years (DZ). Dental casts were scanned using a contact-type 3D scanner, PICZA interfaced to a personal computer running 3D-Rugle3 software. Data were subjected to univariate genetic analysis with the structural equation modelling package, Mx, using the normal assumptions of the twin model. A model incorporating additive genetic (A) and unique environmental (E) variation was found to be the most parsimonious for dental arch breadth and length, and palatal height. Estimates of heritability for dental arch breadth ranged from 0.49 to 0.92, those for arch length from 0.86 to 0.94, and those for palatal height were 0.80 and 0.81, respectively. These results indicate a high genetic contribution to the variation in dental arch dimensions in mainly teenage twins.

Contribution of genetic and environmental factors to variation in body compartments - a twin study in adults

This study aimed at analyzing the contribution of genetic and environmental factors on phenotypic variation of various traits of body composition. Subjects were 30 same-sexed pairs of twins including 20 monozygous (MZ) and 10 dizygous (DZ) pairs, aged 19-62 years. Zygosity was determined by DNA typing and morphological diagnosis. Body composition parameters (fat mass FM, lean body mass LBM, body cell mass BCM, extracellular mass ECM, total body water TBW, extracellular water ECW, and intracellular water ICW) were estimated by tetrapolar bioelectrical impedance analysis. Potential environmental factors influencing body composition (number of children, sporting activity and smoking behaviour) were determined by questionnaires. Heritabilities for traits of body composition were calculated by use of the twin method. Intraclass correlation is > 0.80 for the variation of LBM, BCM, ECM, TBW, ECW, and ICW in both MZ and DZ twins. Estimated heritability (h2) for FM, LBM, BCM, ECW, TBW, ECW, and ICW is 65%, 77%, 79%, 83%, 76%, 68%, and 82%, respectively. The h2 values for FM and LBM are consistent with those reported in other twin studies. For BCM, ECM, ECW and ICW, no comparative h2 estimates exist. Within-pair differences in body compartments do not change with increasing age in MZ and DZ twin pairs (p > 0.05). Stepwise multiple regression analyses indicate that zygosity, age, sex, number of children, sporting level and smoking behaviour do not significantly predict within-pair differences for weight, BMI, FM, LBM, TBW, ECW and ICW (each, p > 0.05). In contrast, sex and the number of children explain together 27% of observed within-pair differences for BCM. Zygosity is the only significant predictor of within-pair differences for ECM and height, explaining 20% (p = 0.008) and 36% of variance, respectively (p < 0.0001). Results indicate that genetic factors exert stronger influences on body composition than the considered environmental traits.

The epidemiology of sudden infant death syndrome

Background: Twins compared to singletons are at increased risk of sudden infant death syndrome (SIDS). Aims: To compare the epidemiology of SIDS in twins and singletons and to test the...

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

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. To determine the influence of genetic factors on IgE responses to specific allergens of Alternaria. 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. 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). 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.