Genetic and environmental factors affecting self-esteem from age 14 to 17: a longitudinal study of Finnish twins

BACKGROUND: We analysed genetic and environmental influences on self-esteem and its stability in adolescence. METHOD: Finnish twins born in 1983-1987 were assessed by questionnaire at ages 14 (n = 4132 twin individuals) and 17 years (n = 3841 twin individuals). Self-esteem was measured using the Rosenberg global self-esteem scale and analyzed using quantitative genetic methods for twin data in the Mx statistical package. RESULTS: The heritability of self-esteem was 0.62 [95% confidence interval (CI) 0.56-0.68] in 14-year-old boys and 0.40 (95% CI 0.26-0.54) in 14-year-old girls, while the corresponding estimates at age 17 were 0.48 (95% CI 0.39-0.56) and 0.29 (95% CI 0.11-0.45). Rosenberg self-esteem scores at ages 14 and 17 were modestly correlated (r = 0.44 in boys, r = 0.46 in girls). In boys, the correlation was mainly (82%) due to genetic factors, with residual co-variation due to unique environment. In girls, genetic (31%) and common environmental (61%) factors largely explained the correlation. CONCLUSIONS: In adolescence, self-esteem seems to be differently regulated in boys versus girls. A key challenge for future research is to identify environmental influences contributing to self-esteem during adolescence and determine how these factors interact with genetic influences.     

Genetic regulation of growth from birth to 18 years of age: The Swedish young male twins study

Growth is a complex process, and only little is known on the genetic regulation of it. We analyzed the effect of genetic and environmental factors on growth in a longitudinal Swedish cohort of 231 monozygotic and 144 dizygotic twin pairs born 1973–1979 with length or height measured annually from birth to age 18. The data were analyzed by two different multivariate variance component models for twin data using the Mx statistical package. At birth and 1 year of age, a substantial part of the variation in length was because of common environment (50 and 57%, respectively) and the effect of genetic factors was minor. After 2 years of age, 91–97% of the variation of height could be explained by genetic differences whereas the rest was because of environmental variation not shared by twins. The genetic correlation between heights at ages 2 and 18 was 0.73 (95% confidence intervals 0.68–0.77) showing that 53% of the genes affecting height at these ages are the same or closely linked; with increasing age the correlation with genetic effects at age 18 become subsequently stronger. Especially in mid‐childhood, growth was largely regulated by the same genetic factors. During puberty new genetic factors started to affect height, but also genetic variation affecting height at previous ages remained. These results suggest that genetic regulation of growth is rather uniform, which is encouraging for further efforts to identify genes affecting growth. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.     

Genetics of pre-pubertal growth: A longitudinal study of Japanese twins

Background: Genetic factors explain a major part of the variation of adult stature, but little is still known on the genetics of growth, especially in non-Caucasian populations.

Aim: To analyse the quantitative genetics of pre-pubertal growth in Japanese children.

Subjects and methods: Data from birth until 11 years of age were collected on 349 complete twin pairs based on previously recorded height measures. The data were analysed using two different multivariate models by the Mx statistical package.

Results: No major sex differences were found and thus boys and girls were analysed together. Since 1 year of age, genetic factors explained from 42–71% and environmental factors shared by co-twins from 14–33% of the variation of height. Genetic continuity of height was high and 75% of the genetic variance was shared since 1 year of age. Environmental factors affecting height showed weaker correlations between early and late childhood than genetic factors.

Conclusion: Growth from early to late childhood is largely regulated by the same set of genes. However, also environmental factors shared by co-twins are important for growth. Identifying specific environmental factors affecting growth has potentially important public health implications, even in an affluent society such as Japan.     

Genetic and environmental influences on pubertal timing assessed by height growth

Secular trends towards earlier puberty, possibly caused by new environmental triggers, provide a basis for periodic evaluation of the influence and interaction of genetic and environmental effects on pubertal timing. In such studies, a practical marker that reflects timing of puberty in both genders needs to be used. We investigated genetic and environmental influences on pubertal timing by using change in the relative height between early and late adolescence (HD:SDS, height difference in standard deviations) as a new marker of pubertal timing. HD:SDS correlated well with age at peak height velocity in a population of men and women with longitudinal growth data. In 2,309 twin girls and 1,828 twin boys, HD:SDS was calculated between height SDs at age 11.5 and 17.5, and 14.0 and 17.5 years, respectively. Quantitative genetic models for twin data were fitted to estimate the genetic contribution to HD:SDS. We also investigated whether the same genetic factors influenced individual differences between HD:SDS and development of secondary sex characteristics prospectively collected by pubertal development scale (PDS). Genetic effects contributed to 86 and 82% of the variance in HD:SDS in girls and boys, respectively, when using the same model including additive genetic and specific environmental factors. In girls, 30% and in boys, 49% of the genetic factors affecting PDS and HD:SDS were the same. Future comparison of the results of periodic evaluations allows estimation of possible changes in the effects of environment on timing of puberty. In such studies, HD:SDS can be used as a practical marker of pubertal timing. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.     

Genetic and Environmental Causes of Tracking in Explosive Strength during Adolescence

Purpose: To determine whether the observed phenotypic stability in explosive strength during adolescence, as measured by inter-age correlations in vertical jump (VTJ), is mainly caused by genetic and/or environmental factors. Methods: Subjects are from the Leuven Longitudinal Twin Study (LLTS) (n = 105 pairs, equally divided over five zygosity groups). VTJ data were aligned on age at peak height velocity (APHV) to attenuate the temporal fluctuations in inter-age correlations caused by differences in timing of the adolescent growth spurt. Simplex models were fitted using structural equation modelling. Results: After aligning the data on APHV, the annual inter-age correlations show a clear simplex structure over a 4 year interval. The best fitting models included additive genetic and unique environmental sources of variation. Heritability estimates ranged between 60.8% (CI 37.7%–77.2%) and 87.3% (CI 74.2%–94.0%) for boys and between 76.5% (CI 56.7%–89.0%) and 88.6% (CI 77.8%–94.1%) for girls. Up to 56.4% and 62.8% of the total variation at the last measurement occasion is explained by additive genetic factors that already explained a significant amount of variation at previous measurement occasions in boys and girls respectively. It thus can be concluded that the observed stability of explosive strength during adolescence is mainly caused by a stable genetic influence in boys and girls. Conclusions: Additive genetic factors seem to be the main cause of the observed phenotypic stability in VTJ performance in boys and girls during adolescence.     

Contributions of Genes and Environments to Stability and Change in Externalizing and Internalizing Problems During Elementary and Middle School

We examined longitudinally collected behavioral reports by teachers on a unique twin sample at the ages of 7, 8, 9, 10, 11, and 12 years. As twin and adoption studies implicate the role of genetic influence on behavioral problems found to be stable in epidemiological samples, the current study employs a developmental behavior genetic model to examine the extent to which genetic and environmental contributions to problem behaviors are stable and/or change during development. In this sample of 410 monozygotic (MZ) and 354 dizygotic (DZ) twins, MZ twins were rated as more similar than DZ twins on average. In general, boys were more frequently rated as displaying externalizing behaviors than were girls across each of the six observations, while girls’ internalizing problems were found not to be significantly different from boys’. For both sexes, stability in externalizing problem behaviors was due to a single common genetic factor whose effects acted pleiotropically at each age in the presence of unique environmental influences that were transmitted from age-to-age. Change was largely due to uncorrelated age-specific non-shared environmental and additive genetic effects. Contributions to stability for internalizing problems were due to age-to-age transmission of earlier expressed genetic effects. Change for girls and boys internalizing problems were largely due to environmental experiences unique to siblings along with uncorrelated age-specific genetic effects. These results further inform the notion that individual environments are important factors in the etiology of problem behaviors, but suggest that heritable contributions to phenotypic stability are largely the same across middle childhood and early adolescence. Clinical implications of these findings are discussed.     

Causes of Stability of Aggression from Early Childhood to Adolescence: A Longitudinal Genetic Analysis in Dutch Twins

This study investigated the contribution of genetic and environmental influences on the stability of aggressive behavior from early childhood to adolescence. Two developmental models, the simplex model and the common factor model, were tested to study the underlying processes of stability and change. Measures of aggressive behavior (AGG) were obtained from maternal CBCL data as part of a large ongoing longitudinal study of the Netherlands Twin Registers (NTR) and included data from 6488 three-year-old twin pairs, 5475 seven-year-old twin pairs, 2983 ten-year-old twin pairs, and 1509 twelve-year-old twin pairs. AGG showed moderate to high stability during childhood. The stability coefficients ranged from 0.41 to 0.77 across varying intervals. Averaged across boys and girls, genetic factors accounted for approximately 65% of the total stability. Longitudinal genetic analysis indicated a simplex model for genetic effects, which suggests a dynamic development process consisting of transmission of existing genetic effects interacting with new genetic influences. This is especially true at age 7, when the influence of new genetic factors was large. Shared environmental factors accounted for approximately 25% of phenotypic stability, and it seemed that a stable set of the same shared environmental factors underlay the development of AGG. Nonshared environmental factors, when important, are age specific. Sex-specific differences for stability were identified. For boys, genetic influences were greater, whereas for girls shared environmental factors were more important. These data support the idea that both genetic and environmental influences play a role in the stability of AGG from age 3 to 12.     

Changes in genetic and environmental influences on trait anxiety from middle adolescence to early adulthood

Background

Middle adolescence to early adulthood is an important developmental period for the emergence of anxiety. Genetically-influenced stable traits are thought to underlie internalizing psychopathology throughout development, but no studies have examined changes in genetic and environmental influences on trait anxiety during this period.

Method

A longitudinal twin study design was used to study same-sex twin pairs (485 monozygotic pairs, 271 dizygotic pairs) at three ages, 14, 18, and 21 years, to examine developmental shifts in genetic and environmental effects on trait anxiety.

Results

The heritability of trait anxiety increased with age, particularly between ages 14 and 18, no significant new genetic influences emerged after age 14, and the genetic influences were highly correlated across the three ages, supporting developmentally stable genetic risk factors. The environmental effects shared by members of a family decreased in influence across adolescence, while the influence of environmental effects unique to each individual twin remained relatively stable over the course of development and were largely age-specific.

Limitations

The twin study design does not inform about specific genes and environmental risk factors.

Conclusions

Genetic influences increased in importance from middle to late adolescence but common genetic factors influenced trait anxiety across the three ages. Shared environmental influences decreased in importance and demonstrated negligible influence by late adolescence/early adulthood. Nonshared environmental effects were almost entirely age-specific. These findings support the importance of developmentally-sensitive interventions that target shared environmental factors prior to middle adolescence and shifting non-shared environmental risks at each age.     

Genetic and Environmental Influences on Stages of Alcohol Use Across Adolescence and into Young Adulthood

The progression to alcohol dependence unfolds across multiple stages, including the decision to initiate use, the development of regular patterns of use, and (for some individuals) the subsequent development of problems associated with alcohol use. Using data from two population-based, longitudinal twin studies, FinnTwin16 (FT16) and FinnTwin12 (FT12), we applied multiple stage genetic models (Heath et al., Twin Res. 5 (2002) 113) to better understand the extent to which genetic and environmental influences impact the initiation of alcohol use, frequency of use in adolescence and young adulthood, and alcohol problems in young adulthood. Shared environmental factors played a large role in initiation, and a more moderate role on frequency of use, and it was largely the same influences acting across these stages of use. However, there was no significant evidence of shared environmental influences on alcohol problems in early adulthood. Problems were largely influenced by genetic factors that overlapped with genetic influences on frequency of use. Unique environmental factors were largely specific to each stage, with some overlap between alcohol problems and frequency of use at age 25.     

Relationships among tempo of maturation,midparent height,and growth in height of adolescent boys and girls

The influence of rate of skeletal maturation and midparent height on growth in height during adolescence was analyzed on longitudinal data for 184 boys and 166 girls from the Wrocław Growth Study. Seven biological parameters describing the shape of the growth curve in stature were derived from the Preece–Baines model 1 applied to individual serial data. Rate of skeletal maturation inferred from the difference between chronological and skeletal ages at 12 years in girls and 14 in boys. Principal components analysis of the biological parameters extracted three factors for boys and four for girls. The factors explained 90% and 97% of the total variance in boys and girls, respectively. The factors reflected attained size and the timing and intensity of the adolescent spurt in height. Multiple regression showed a high relationship between skeletal maturation rate, midparent height, and principal component scores. Three aspects of adolescent growth: size, timing, and intensity show an apparent sex difference. The timing and intensity of the spurt are highly affected by tempo of maturation in girls, but less so than in boys. It might suggest in girls a less efficient compensatory effect for reduced length of overall growth period in early maturers that increases height gain. Midparent height influences the size component during the spurt, thus adjusting the height parameters. The dependency between attained stature (height at take‐off, PHV, and adult stature), timing, and initial intensity of the growth spurt of daughters and midparent height is greater than in sons. Am. J. Hum. Biol. 13:15–22, 2001. © 2001 Wiley‐Liss, Inc.     

Genetic and Environmental Correlations Between Body Mass Index and Waist Circumference in China: The Qingdao Adolescent Twin Study

We aimed to analyze how genetic and environmental factors account for variations in body mass index (BMI), waist circumference (WC) and their mutual correlation in Chinese children. We measured BMI and WC in 588 pairs of twins (53 % monozygotic twins) aged 8–17 years and applied structural equation modeling to the data. For the younger children (8–12 years of age), heritability estimates of BMI were 0.56 for boys and 0.69 for girls; for the older children (13–17 years of age), the corresponding figures were 0.64 and 0.71, respectively. We observed moderate heritability estimates in WC: the corresponding figures were 0.24 and 0.56 for the younger children, and 0.27 and 0.33 for the older children, respectively. The heterogeneity test for genetic variance of BMI and WC was statistically significant between the two age groups for both sexes (p < 0.001). The proportions of BMI and WC variations due to shared and non-shared environmental factors remained stable during childhood in both sexes. Bivariate genetic analyses showed that genetic correlations between BMI and WC were strong for the younger children (r_g = 0.75 for boys, r_g = 0.98 for girls) and the older children (r_g = 1.0 for both boys and girls). Both sexes showed moderate non-shared environmental correlations in the two age groups, whereas shared environmental correlations––except among male younger children––were not statistically significant. Genetic factors play an important role in variations in BMI and WC during childhood. Common genetic and non-shared environmental factors explained most of the association between BMI and WC for both boys and girls.     

Thought Problems from Adolescence to Adulthood: Measurement Invariance and Longitudinal Heritability

This study investigates the longitudinal heritability in Thought Problems (TP) as measured with ten items from the Adult Self Report (ASR). There were ~9,000 twins, ~2,000 siblings and ~3,000 additional family members who participated in the study and who are registered at the Netherlands Twin Register. First an exploratory factor analysis was conducted to examine the underlying factor structure of the TP-scale. Then the TP-scale was tested for measurement invariance (MI) across age and sex. Next, genetic and environmental influences were modeled on the longitudinal development of TP across three age groups (12–18, 19–27 and 28–59 year olds) based on the twin and sibling relationships in the data. An exploratory factor analysis yielded a one-factor solution, and MI analyses indicated that the same TP-construct is assessed across age and sex. Two additive genetic components influenced TP across age: the first influencing TP throughout all age groups, while the second arises during young adulthood and stays significant throughout adulthood. The additive genetic components explained 37% of the variation across all age groups. The remaining variance (63%) was explained by unique environmental influences. The longitudinal phenotypic correlation between these age groups was entirely explained by the additive genetic components. We conclude that the TP-scale measures a single underlying construct across sex and different ages. These symptoms are significantly influenced by additive genetic factors from adolescence to late adulthood.     

Genetic and Environmental Causes of Variation in Trait Resilience in Young People

The aim of this multi-informant twin study was to determine the relative role of genetic and environmental factors in explaining variation in trait resilience in adolescents. Participants were consenting families (N = 2,638 twins in 1,394 families), from seven national cohorts (age 12–18 years, both sexes) of monozygotic and dizygotic twins reared together. Questionnaire data on the adolescents’ Ego-resilience (ER89) was collected from mothers, fathers and twins, and analysed by means of multivariate genetic modelling. Variance in trait resilience was best represented in an ADE common pathways model with sex limitation. Variance in the latent psychometric resilience factor was largely explained by additive genetic factors (77% in boys, 70% in girls), with the remaining variance (23 and 30%) attributable to non-shared environmental factors. Additive genetic sources explained more than 50% of the informant specific variation in mothers and fathers scores. In twins, additive and non-additive genetic factors together explained 40% and non-shared environmental factor the remaining 60% of variation. In the mothers’ scores, the additive genetic effect was larger for boys than for girls. The non-additive genetic factor found in the twins’ self ratings was larger in boys than in girls. The remaining sex differences in the specific factors were small. Trait resilience is largely genetically determined. Estimates based on several informants rather than single informants approaches are recommended.     

Genetic and Environmental Influences on the Stability of Withdrawn Behavior in Children: A Longitudinal,Multi-informant Twin Study

We examined the contribution of genetic and environmental influences on the stability of withdrawn behavior (WB) in childhood using a longitudinal multiple rater twin design. Maternal and paternal ratings on the withdrawn subscale of the Child Behavior Checklist (CBCL) were obtained from 14,889 families when the twins were 3, 7, 10 and 12 years old. A longitudinal psychometric model was fitted to the data and the fit of transmission and common factor models were evaluated for each variance component. WB showed considerable stability throughout childhood, with correlation coefficients ranging from about .30 for the 9-year time interval to .65 for shorter time intervals. Individual differences in WB as observed by the mother and the father were found to be largely influenced by genetic effects at all four time points, in both boys (50–66%) and girls (38–64%). Shared environmental influences explained a small to modest proportion (0–24%) of the variance at all ages and were slightly more pronounced in girls. Non-shared environmental influences were of moderate importance to the variance and slightly increased with age, from 22–28% at age 3 to 35–41% at age 12 years. The stability of WB was largely explained by genetic effects, accounting for 74% of stability in boys and 65% in girls. Shared environmental effects explained 7% (boys) and 17% (girls) of the behavioral stability. Most shared environmental effects were common to both raters, suggesting little influence of rater bias in the assessment of WB. The shared environmental effects common to both raters were best described by a common factor model, indicating that these effects are stable and persistent throughout childhood. Non-shared environmental effects accounted for the remaining covariance over time. Edited by Hermine Maes.     

Genetic Innovation and Stability in Externalizing Problem Behavior Across Development: A Multi-Informant Twin Study

The use of cross-informant ratings in previous longitudinal studies on externalizing behavior may have obscured the presence of continuity of genetic risk. The current study included latent factors representing the latent estimates of externalizing behavior based on both parent and self-report which eliminated rater-specific effects from these latent estimates. Symptoms of externalizing behavior of 1,480 Swedish twin pairs were obtained at ages 8–9, 13–14, 16–17 and 19–20 both by parent and self-report. Mx modeling was used to estimate additive genetic, shared and specific environmental influences. Genetic continuity was found over the entire developmental period as well as additional sources of genetic influence emerging around early and late adolescence. New unique environmental effects (E) on externalizing behavior arose early in adolescence. The results support both the presence of genetic continuity and change in externalizing behavior during adolescence due to newly emerging genetic and environmental risk factors.     

Genetic and Environmental Factors in Breakfast Eating Patterns

Despite many studies on the prevalence of breakfast eating, we know little about factors that determine breakfast eating patterns. Our aim was to find out to which extent breakfast eating frequency is influenced by genetic and environmental factors using twin and twin-family models in a population sample of 16-year-old twins (n = 5250) and their parents (n = 4663). In common effects sex-limitation models, additive genetic effects explained 41% (95% CI: 21-63%) of the variance in breakfast eating in girls and 66% (95% CI: 47-79%) in boys, and common environmental effects 45% (95% CI: 23-62%) in girls and 14% (95% CI: 5-29%) in boys. Of twin-family models, phenotypic assortment models fitted the data best. Heritability estimates increased somewhat (72%, 95% CI: 46-98% in girls and 63%, 95% CI: 38-89%) in boys. Common family environment remained substantial in both sexes. Cultural transmission was nonsignificant. The relative influence of genetic and family factors on adolescent breakfast eating frequency differs by sex and is generation-specific.     

Genetic and Environmental Factors Influencing BMI Development from Adolescence to Young Adulthood

BMI increases progressively from adolescence to young adulthood. The aims of the present study were firstly, to investigate the extent to which genetic and environmental influences account for differences in BMI trajectories during this period, and secondly to examine whether boys and girls show divergences in these influences, as their BMI normally start differing across adolescence. The study sample consisted of 4,915 monozygotic and like- and unlike-sex dizygotic twins, born between 1975 and 1979. Data on BMI was gathered when twins were on average 16.1, 17.1, 18.6 and 24.4 years old. Genetic and environmental influences on the BMI trajectories were modeled using a latent growth curve approach. The results showed that the heritability of BMI decreased slightly after the adolescence period, from ≈80 to 70%. BMI transition from adolescence to young adulthood was best described by a quadratic trajectory that was highly accounted (61.7–86.5%) for by additive genetic influences. Genetic influences on BMI level showed a low correlation with those on the trend in BMI with age indicating that different sets of genes underlie the change of BMI during this period. Importantly, the analyses also evidenced that different genetic and environmental influences may underlie boys and girls evolution. In conclusion, our results suggested specific genetic influences accounting for the BMI rate-of-change from adolescence to young adulthood. This indicates that the specific genes behind BMI level may not be the same as the genes affecting BMI change which should be taken into account in further efforts to identify these genes.     

Genetic and environmental determinants of the cardio-respiratory response to submaximal exercise--a six-year follow-up study of twins

The fat-free mass and the ventilatory and cardiac frequency responses to submaximal exercise have been assessed longitudinally over six years in a total of 65 identical and non-identical boy and girl twin pairs. Exercise ventilation at rates of work below the anaerobic threshold was independent of the genetic and environmental factors which were investigated. The anaerobic threshold increased with age. The fat-free mass and the exercise cardiac frequency were subject to both genetic and environmental control with the genetic component predominating initially. The subsequent environmental component was larger for non-identical than for identical twin pairs and for boys than for girls. It is concluded that in identical twin boys by the time they reach adolescence the performance during submaximal exercise has a material environmental component. There appears to be interaction between the genetic and environmental components.     

Sex steroids at birth: genetic and environmental variation and covariation.

Three sex-steroids (estradiol, progesterone, & testosterone) were assayed from the umbilical cord blood of 58 same-sex twin pairs in an investigation of the effects of sex, as well as genetic and environmental factors, on neonatal hormone levels. Although significant mean differences were found between boys and girls for both testosterone and progesterone, sex appeared to account for very little of the total variation for any of the hormones. Results showed that genetic influences significantly affected within-sex variation in both estradiol and progesterone levels, while variations in the intrauterine (shared twin) environment accounted primarily for differences in levels of testosterone. Moderate correlations were also found among the three hormones. Multivariate biometrical analyses revealed these relationships to be explained by an underlying general factor of nonshared environmental influences affecting all three hormones. Genetic factors appeared to be specific to each hormone rather than correlated across hormones. These results suggest not only that genes are operating at this early age, but also that maternal and other prenatal factors (e.g., placental effects, uterine position) have a significant role in variations of sex-steroids and possibly on later behaviors.     

Trends in eczema in the first 18 years of life: results from the Isle of Wight 1989 birth cohort study

Background Trends in the prevalence of eczema in the course of childhood and adolescence are not clear although often a net remission during childhood is assumed. Objectives To investigate the dynamics of change in eczema from 1 to 18 years in a prospective study and to understand the influence of gender and atopy. Methods Detailed information regarding eczema were collected at ages 1, 2, 4, 10 and 18 years from the 1989 Isle of Wight birth cohort (n=1456). Skin prick testing was performed at 4, 10 and 18 years of age. The 12‐month period prevalence, positive and negative transitions (defined as change in disease status in two consecutive study assessments) were stratified by gender and atopic status. Results The period prevalence of eczema from birth to 18 years of age remained relatively constant (11.9–14.2%) with minimal remission. Up to 10 years of age, gender did not influence prevalence. From 10 to 18 years, eczema became more prevalent among girls (16.3% for girls vs. 8.3% for boys, P<0.001) as a result of a greater positive transition in girls (9.4% for girls vs. 4.3% for boys, P=0.001) and greater negative transition in boys (65.4% for boys vs. 50% for girls, P=0.04). The higher positive transition of eczema in girls was most pronounced for non‐atopic eczema (5.9% for girls vs. 1.5% for boys, P=0.002). Conclusions We found only a minimal reduction in the prevalence of eczema during childhood and adolescence. During adolescence, more girls develop eczema and more boys outgrow it suggesting a role for gender‐specific pubertal factors. Cite this as: A. H. Ziyab, A. Raza, W. Karmaus, N. Tongue, H. Zhang, S. Matthews, S. H. Arshad and G. Roberts, Clinical & Experimental Allergy, 2010 (40) 1776–1784.