The present study assessed the prevalence of asthma and allergy, and estimated the importance of genetic and environmental influences on asthma and allergy liability and their association. Longitudinal data on self-reported, doctor-diagnosed asthma and allergy were collected in over 14,000 individuals registered with the Netherlands Twin Register. Structural equation modeling was used for univariate and bivariate genetic analyses on data from twins, their siblings, and parents. Results showed no sex, age, and minimal birth cohort effects for asthma prevalence (11.8%). For allergy, prevalence was higher in women (19.8%) than in men (13.9%). Allergy prevalence at ages 22, 23, and 24 years increased from the 1970 to the 1980 birth cohort. The prevalence of allergy, but not of asthma, was higher in nontwin siblings than in twins. No assortative mating was observed. High (broad-sense) heritabilities were found for asthma (75%) and allergy (66%), with evidence for nonadditive genetic effects in asthma. The association between asthma and allergy (correlation = .65) was largely due to common genes (70%). No sex differences in genetic architecture were found. In conclusion, the prevalence of allergy but not of asthma increased in recent years. Individual differences in the liability to asthma, allergy and their co-occurrence are for a large part accounted for by differences in genetic background. Nonadditive gene action is important, which may have consequences for gene hunting strategies.

Inherited disorders of mitochondrial oxidative phosphorylation are the most common group of inborn errors of metabolism and cause a wide range of clinical presentations. Mitochondrial DNA encodes 13 protein subunits required for oxidative phosphorylation plus 22 transfer RNAs and two ribosomal RNAs, and mutations in most of these genes cause human disease. Nuclear genes encode most of the protein subunits and all other proteins required for mitochondrial biogenesis and mitochondrial DNA replication and expression. Mutations in 64 nuclear genes and 34 mitochondrial genes are now known to cause mitochondrial disease and many novel mitochondrial disease genes await discovery. The genetic complexity of oxidative phosphorylation means that maternal, autosomal recessive, autosomal dominant and X-linked modes of inheritance can occur, along with de novo mutations. This complexity presents a challenge in planning efficient molecular genetic diagnosis of patients with suspected mitochondrial disease. In some situations, clinical phenotype can be strongly predictive of the underlying genotype. However, more often this is not the case and it is usually helpful, particularly with pediatric patients, to determine whether the activity of one or more of the individual oxidative phosphorylation enzymes is deficient before proceeding with mutation analysis. In this review we will summarize the genetic bases of mitochondrial disease and discuss some approaches to integrate information from clinical presentation, laboratory findings, family history, and imaging to guide molecular investigation.

The importance of using multiple polymorphic genetic markers to determine unambiguously whether a twin pair is monozygotic (MZ) or dizygotic (DZ) has long been recognized. Concordance among a set of markers is used as evidence of monozygosity, as it would be improbable for DZ twins to be concordant at a large number of polymorphic loci. Several sources give a formula for the probability of two DZ twins sharing the same genotype at a locus, assuming knowledge of allele frequencies but not of either twin's genotype; this probability can be used to determine whether a set of markers will reliably distinguish between MZ and DZ status in a randomly selected twin pair. If the shared genotype is known, however, the likelihood-ratio test (LRT) of the null hypothesis of dizygosity against the alternative hypothesis of monozygosity takes into account the observed genotype and, by the Neyman-Pearson lemma, is the most powerful test of its size. The LRT is equivalent to conditioning on the genotype of one of the twins, and computing the probability, assuming DZ status, of the other twin sharing that genotype. The resulting p values are frequently lower than those produced by the unconditional probability, especially if rare alleles are observed. The unconditional probability can be recapitulated from conditional probabilities by averaging across all of the conditioned sibling's possible genotypes. To illustrate properties of the LRT applied to multiple markers, the probability distribution of the LRT p value is computed from allele frequencies of twelve unlinked markers published in Elbaz et al. (2006) and compared with the p value computed from unconditional probabilities.

Background: Our research group recently reported that aorto-radial (radial) and aorto-dorsalis-pedis (foot) pulse wave velocity (PWV) as proxies of arterial stiffness are substantially heritable in healthy youth. This article aimed at uncovering the genetic contributions of adhesion molecules, key members in the inflammatory process, to PWV in these young individuals. Methods: Radial and foot PWV were noninvasively measured with applanation tonometry in 702 black and white subjects (42% blacks, mean age 17.7 ± 3.3 years) from the Georgia Cardio vascular Twin Study. Eight functional polymorphisms from genes for E-selectin (SELE), P-selectin (SELP), intercellular adhesion molecules-1 (ICAM1), and vascular cell adhesion molecules-1 (VCAM1) were genotyped. Results: Youth with Ser290Asn or Asn290Asn genotype (SELP) compared to those with Ser290Ser had an increase in both radial and foot PWV (6.61 ± 0.07 vs. 6.41 ± 0.05 m/s, p = .026; 7.22 ± 0.05 vs. 7.04 ± 0.04 m/s, p = .007). TT homozygotes of rs2244529 (SELP) had higher foot PWV (7.28 ± 0.07 vs. 7.06 ± 0.03 m/s, p = .002) than CT heterozygotes and CC homozygotes. There appeared to be a decrease in foot PWV in youth with the 241Arg allele (ICAM1) as compared to those without (6.96 ± 0.08 vs. 7.14 ± 0.03 m/s, p = .005). For the Asp693Asp (C to T) polymorphism (VCAM1), CC genotype had higher foot PWV than CT and TT genotypes (7.18 ± 0.04 vs. 6.95 ± 0.06 m/s, p < .0001). There was an epistatic interaction between Ser290Asn, Gly241Arg, and Asp693Asp on foot PWV (p = .017), explaining 3.6% variance of the foot PWV. Conclusion: Genetic variation of adhesion molecules may be implicated in the development of arterial stiffness. Screening for adhesion molecule polymorphisms may help identify high-risk youth.

A consistent finding from twin studies is that the environment shared by family members does not contribute to the variation in susceptibility to asthma. At the same time, it is known that environmental risk factors that are shared by family members are associated with the liability for asthma. We hypothesize that the absence of a main effect of shared environmental factors in twin studies can be explained by gene–environment interaction, that is, that the effect of an environmental factor shared by family members depends on the genotype of the individual. We explore this hypothesis by modeling the resemblance in asthma liability in twin pairs as a function of various environmental risk factors and test for gene–environment interaction. Asthma data were obtained by parental report for nearly 12,000 5-year-old twin pairs. A series of environmental risk factors was examined: birth cohort, gestational age, time spent in incubator, breastfeeding, maternal educational level, maternal smoking during pregnancy, current smoking of parents, having older siblings, and amount of child care outside home. Results revealed that being a boy, born in the 1990s, premature birth, longer incubator time, and child care outside home increased the risk for asthma. With the exception of premature birth, however, none of these factors modified the genetic effects on asthma. In very premature children shared environmental influences were important. In children born after a gestation of 32 weeks or more only genetic factors were important to explain familial resemblance for asthma.

Alcohol dependence symptoms and consumption measures were examined for stability and heritability. Data were collected from 12,045 individuals (5376 twin pairs, 1293 single twins) aged 19 to 90 years in telephone interviews conducted in three collection phases. Phases 1 and 2 were independent samples, but Phase 3 targeted families of smokers and drinkers from the Phase 1 and 2 samples. The stability of dependence symptoms and consumption was examined for 1158 individuals interviewed in both Phases 1 and 3 (mean interval = 11.0 years). For 1818 individuals interviewed in Phases 2 and 3 (mean interval = 5.5 years) the stability of consumption was examined. Heritability was examined for each collection phase and retest samples from the selected Phase 3 collection. The measures examined were a dependence score, based on DSM-IIIR and DSM-IV criteria for substance dependence, and a quantity × frequency measure. Measures were moderately stable, with test–retest correlations ranging from .58 to .61 for dependence and from .55 to .64 for consumption. However, the pattern of changes over time for dependence suggested that the measure may more strongly reflect recent than lifetime experience. Similar to previous findings, heritabilities ranged from .42 to .51 for dependence and from .31 to .51 for consumption. Consumption was significantly less heritable in the younger Phase 2 cohort (23–39 years) compared to the older Phase 1 cohort (28–90 years).

One thousand and seventy three pairs of adult monozygotic (MZ) twins and 895 pairs of same sex adult dizygotic (DZ) twins from the United Kingdom (UK) completed the Humor Styles Questionnaire: a 32-item measure which assesses two positive and two negative styles of humor. MZ correlations were approximately twice as large as DZ correlations for all four humor styles, and univariate behavioral genetic model fitting indicated that individual differences in all of them can be accounted for entirely by genetic and nonshared environmental factors, with heritabilities ranging from .34 to .49. These results, while perhaps not surprising, are somewhat at odds with a previous study that we conducted in North America (Vernon et al., in press) in which genetic factors contributed significantly to individual differences in the two positive humor styles, but contributed far less to the two negative styles, variance in which was instead largely due to shared and nonshared environmental factors. We suggest that differences between North American and UK citizens in their appreciation of different kinds of humor may be responsible for the different results obtained in these two studies.

Disorders of eye development such as microphthalmia and anophthalmia (small and absent eyes respectively), anterior segment dysgenesis where there may be pupillary and iris anomalies, and associated cataract and glaucoma, often lead to visual impairment or blindness. Currently treatment options are limited, as much is unknown about the molecular pathways that control normal eye development and induce the aberrant processes that lead to ocular defects. Mutation detection rates in most of the known genes are generally low, emphasizing the genetic heterogeneity of developmental ocular defects. Identification of the disease genes in these conditions improves the clinical information available for affected individuals and families, and provides new insights into the underlying biological processes for facilitation of better treatment options. Investigation of chromosomal rearrangements associated with an ocular phenotype has been especially powerful for disease gene identification. Molecular characterization of such rearrangements, which pinpoints the region by physically disrupting the causative gene or its regulatory sequences, allows for rapid elucidation of underlying genetic factors that contribute to the phenotype. Genes including PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4 have been identified in this way to be associated with developmental eye disorders. More recently, new methods in chromosomal analysis such as comparative genomic hybridization (CGH) microarray, have also enhanced our ability in disease gene identification.

In an extended twin study we estimated the heritability of fasting HbA1c and blood glucose levels. Blood glucose was assessed in different settings (at home and in the clinic). We tested whether the genetic factors influencing fasting blood glucose levels overlapped with those influencing HbA1c and whether the same genetic factors were expressed across different settings. Fasting blood glucose was measured at home and during two visits to the clinic in 77 healthy families with same-sex twins and siblings, aged 20 to 45 years. HbA1c was measured during the first clinic visit. A 4-variate genetic structural equation model was used that estimated the heritability of each trait and the genetic correlations among traits. Heritability explained 75% of the variance in HbA1c. The heritability of fasting blood glucose was estimated at 66% at home and lower in the clinic (57% and 38%). Fasting blood glucose levels were significantly correlated across settings (0.34 < r < 0.54), mostly due to a common set of genes that explained between 53% and 95% of these correlations. Correlations between HbA1c and fasting blood glucoses were low (0.11 < r < 0.23) and genetic factors influencing HbA1c and fasting glucose were uncorrelated. These results suggest that in healthy adults the genes influencing HbA1c and fasting blood glucose reflect different aspects of the glucose metabolism. As a consequence these two glycemic parameters can not be used interchangeably in diagnostic procedures or in studies attempting to find genes for diabetes. Both contribute unique (genetic) information.

This study reports the first behavioral genetic investigation of the extent to which genetic and/or environmental factors contribute to the relationship between the Big Five personality factors and trait emotional intelligence. 213 pairs of adult monozygotic twins and 103 pairs of same-sex dizygotic twins completed the NEO-PI-R and the Trait Emotional Intelligence Questionnaire (TEIQue). Replicating previous non-twin studies, many significant phenotypic correlations were found between the Big Five factors — especially Neuroticism, Extraversion, and Conscientiousness — and the facets, factors, and global scores derived from the TEIQue. Bivariate behavioral genetic model-fitting analyses revealed that these phenotypic correlations were primarily attributable to correlated genetic factors and secondarily to correlated non-shared environmental factors. The results support the feasibility of incorporating EI as a trait within existing personality taxonomies.

The genetic basis of cardiovascular disease (CVD) is complex and still largely elusive. Plasma lipid concentrations are well-established risk factors for cardiovascular disease (CVD), and have adult heritabilities ranging from 0.48 to 0.87. Estimates for adolescents are slightly higher (range 0.71 to 0.82). To identify loci affecting lipid concentrations across adolescence, we analyzed longitudinal lipid data in a sample of 134 monozygotic and 626 dizygotic twin pairs at ages twelve, fourteen and sixteen, and their siblings, from 760 Australian families. Univariate linkage analysis for each phenotype and time point was supplemented by multivariate analysis across the time points. A genome-wide association scan was also performed on a subset of the subjects (N = 441). The strongest linkage was seen for triglycerides on chromosome 6p24.3 (multivariate –log10p = 6.81; equivalent LOD = 6.13; p = 1.55 × 10–7). Significant linkage was also found for LDL cholesterol on chromosome 2q35 (multivariate –log10p = 5.59; equivalent LOD = 4.53; p = 2.57 × 10–6). In the association analysis, rs10503840 on 8p21.1 was significantly associated with total cholesterol levels at age fourteen (p = 8.24 × 10–7, estimated significance threshold 2.45 × 10–6). Association at p < 2.25 × 10–6 was also found between triglycerides at age 12 and rs10507266, in an intron of THRAP2 (MIM 608771) on 12q24.21; and between HDL-C at age 14 and rs10506325 in an intergenic region of 12q13.13. Suggestive evidence of association at ages twelve and fourteen was found between HDL-C and rs10492859 on 16q23 (p = 2.42 × 10–5 and 2.77 × 10–4, respectively). Further longitudinal genetic studies of cardiovascular risk factors, focused on critical periods of development or change, are needed.

Most epidemiologic studies employ a vacuum cleaner used by a trained technician to collect household allergens. This approach is labor intensive, equipment dependent, and impractical if study subjects reside over a wide geographic area. We examined the feasibility of a self-administered dust collection method, using an electrostatic cloth sent by conventional mail, to obtain allergen measurements. Thirty-two nonasthmatic twins from the California Twin Program wiped areas in the family room, kitchen, and bedroom, according to standardized instructions, and returned the cloths by mail. Allergen concentrations for Der-p-1, Der-f-1, Fel-d-1, and Bla-g-2 were determined using ELISA, and intrahouse and room-to-room concentrations were compared. Der-p-1 and Fel-d-1 were found in most homes, with highest concentrations in bedrooms and kitchens, respectively. Der-f-1 and Bla-g-2 were rarely found. Intrahouse Der-p-1 and Fel-d-1 concentrations were highly correlated and statistically significant (for Der-p-1, bedroom vs. kitchen, p = .0003, bedroom vs. family room, p = .0001, and family room vs. kitchen, p = .002; for Fel-d-1, bedroom vs. kitchen, p = .0004, bedroom vs. family room, p < .0001, and family room vs. kitchen, p = .0001). Reported cat ownership was strongly correlated with household Fel-d-1 concentrations (p < .005). In another comparison from different homes of children enrolled in the La Casa atopy prevention study, allergen concentrations measured from dust collected by a single operator from the left and right half of the same room in 21 homes were compared. Levels of Bla-g-2, Der-p-1, and Fel-d-1 concentrations collected from right and left halves of the same room were highly correlated, with r2 ranging from .7 to .9, and were highly statistically significant (all p values < .01). We conclude that nonintrusive and self-administered dust collection, using commercially available electrostatic dust cloths, sent by conventional mail services, is a promising alternative to technician-collected vacuumed dust for measuring indoor allergens in population-based studies, although further validation of the method is necessary.

It has been reported that prevalence estimates, symptom presentation, and sociocultural risk and protective factors for depression differ between Caucasian and East Asian populations. But, nonetheless, as the vast majority of twin studies of depression symptoms have been carried out using Caucasians, genetic and environmental influences on depression symptoms in East Asians remain poorly understood. In the present study, the Center for Epidemiologic Studies — Depression Scale (CES-D) was administered to 490 pairs of South Korean adolescent and young adult twins (ages: 13–23 years) by telephone interview. In males, monozygotic (MZ) and dizygotic (DZ) twin correlations were similar (.44 vs. .41), suggesting the importance of shared environmental factors in depression symptoms. In females, however, MZ twin correlation was much greater than DZ twin correlation (.40 vs. .23), indicating the importance of genetic influences. The total phenotypic variance for the CES-D was greater in females than in males. Variance components model confirmed sex differences in the magnitude of genetic and environmental influences on depression symptoms: Additive genetic, shared environmental, and individual specific environmental effects in the full model were, res pectively, 12% (95% CI: 0–54%), 32% (95% CI: 0–53%), and 56% (95% CI: 44–70%) in males, and 41% (95% CI: 0–52%), 0% (95% CI: 0–36%), and 59% (95% CI: 48–72%) in females. Similar results were observed when ‘culturally biased’ items of the CES-D were separately analyzed. These variance components estimates for depression symptoms in East Asians overlap those observed in Caucasians.

We expand our previous deterministic power calculations by calculating the required sample size to detect C in ACE models. The theoretical expected value of the maximum log-likelihood for the AE model was derived using two optimisation methods and these gave near-identical results. Theoretical predictions were verified by computer simulation and the results agreed very well. We have developed a user-friendly web-based tool, TwinPower, to perform power calculations to detect either A or C for the classical twin design. This new tool can be found at http://genepi.qimr.edu.au/cgi-bin/twinpower.cgi

As the results of the Human Genome Project are realized, it has become technically possible to identify carriers of numerous autosomal and X-linked recessive disorders. Couples at risk of having a child with one of these conditions have a number of reproductive options to avoid having a child with the condition should they wish. In Australia the haemoglobinopathies are the only group of conditions for which population screening is widely offered and which is government funded. In some Australian states there are also population screening programs for cystic fibrosis and autosomal recessive conditions more common in Ashkenazi Jewish individuals which are generally offered on a user pays basis. It is predicted that as consumer demand increases and testing becomes cheaper, that many people planning or in the early stages of pregnancy will have carrier screening for multiple genetic conditions. This will have significant implications for genetic counseling, laboratory and prenatal testing resources. In addition such screening raises a number of ethical issues including the value of lives of those born with genetic conditions for which screening is available.

The purpose of the present study was to examine the 10 value types from the Portrait Values Questionnaire (PVQ; Schwartz et al., 2001) both at the phenotypic (observed) level as well as the genetic and environmental level. Australian twins (N = 695) completed the PVQ as part of a larger questionnaire battery. Nine of the value types were found to have a genetic component with heritability estimates ranging from 10.8% for power to 38% for conformity. The achievement scale was best explained by environmental factors. The interscale correlations were found to range from –.02 to .70 at the phenotypic level. Of these 45 correlations, 16 were found to be explained by overlapping genetic factors and almost all (41) were found to have significant unique environment correlations.

Several studies report caesarean section (CS) to be a risk factor for childhood asthma. We used data from a large cohort of 5-year-old twins to examine the relationship between mode of birth delivery and asthma. The extent to which an infant is exposed to maternal vaginal flora may protect against the risk of developing asthma. Therefore, we expect a lower rate of asthma in twins born by vaginal delivery (VD) than those born by CS, and a lower rate of asthma in first-born twins compared to second-born twins by VD. Information on mode of delivery was obtained at the time of birth in a survey completed by the mother shortly after delivery. Information on history of asthma diagnosis by a physician was obtained by parental report when the twins were 5 years old. Complete data were available for 6330 first-born and 5438 second-born twins from birth cohorts 1991–2000. Full term first-born twins born by CS had a significantly higher risk of asthma compared to those born by VD, odds ratio = 1.59 (95% CI = 1.23–2.06). No significant differences were observed between CS and VD first-born twins when gestational age was less than 37 weeks, and no significant differences were observed between CS and VD second-born twins at any gestational age. No differences in asthma prevalence were found between first- and second-born twins both born by VD. CS may increase the risk of asthma to full term infants, however, the underlying mechanism is unclear.

Accumulated evidence suggests that social support is influenced by genetic and environmental factors. However, there are little data that examine this issue from Asian samples. We reported results from a preliminary study that examined familial effects on social support in a Chinese adult twin sample. We administered a 10-item social support instrument that measures three dimensions of social support (i.e., objective support, subjective support, and utilization of support) developed for the Chinese population. Two hundred forty-two same-sex twin pairs, where both members of the pair completed the personal interview, were included in the final analysis. Structural equation modeling was used to estimate additive genetic (A), shared environmental (C), and nonshared environmental (E) effects on each dimension of social support. Familial factors (A+C) explained 56.63% [95% CI = 45.48–65.72%] and 42.42% [95% CI = 29.93–53.25%] of the total phenotypic variances of subjective support and utilization of support, respectively. For the objective support, genetic effects did not exist, but common environmental effect explained 37.56% [95% CI = 26.17–48.28%] of the total phenotypic variances. Neither gender nor age effects were seen on any dimension of social support. Except for objective support, genetic factors probably influence variation in subjective support and utilization of support. Shared environmental factors may influence all dimensions of social support.

Common polymorphisms of the CD36 fatty acid transporter gene have been associated with lipid metabolism and cardiovascular disease. Association of a CD36 promoter single nucleotide polymorphism genotype with anthropometry and serum lipids was investigated in normal subjects, and in obese subjects during an 8-week low calorie diet and 6-month weight-maintenance period. 2728 normal female Twins UK subjects (mean body mass index 24.8 ± 4.4 kg/m2; age 47.3 ± 12.5 y) and 183 obese male and female Spanish subjects (mean body mass index 30.6 ± 3.0 kg/m2; age 35.0 ± 5.0 y) were genotyped for the CD36-22674 T/C (rs2151916) promoter single nucleotide polymorphism. In the Twins UK full cohort, the C-allele was associated with lower low density lipoprotein-cholesterol (p = .02, N = 2396). No associations were found in the obese Spanish subjects at baseline, but 6 months after the end of the low-calorie diet, the C-allele was associated with lower total- (p = .03) and low density lipoprotein-cholesterol (p = .01) and higher high density lipoprotein-cholesterol (p = .01). Intake of saturated fatty acids was lower in carriers of the C-allele at baseline, but not significantly so (p = .11). However, 6 months after the end of the low-calorie diet, elements of the lipid profile were correlated with saturated fatty acid intake: total cholesterol r = .21, p = .060; low density lipoprotein-cholesterol: r = .25, p = .043; high density lipoprotein-cholesterol: r= –.26, p = .007. CD36 promoter SNP allele –22674C is therefore associated with lower serum low-density lipoprotein-cholesterol in normal female twins and with improved lipid profile during weight loss and maintenance in obese subjects.