ABSTRACT
We explored the genetic architecture of metabolic risk factors of cardiovascular diseases (CVDs) and their clustering in Chinese boys and girls. Seven metabolic traits (body mass index [BMI], waist circumference [WC], systolic blood pressure [SBP], diastolic blood pressure [DBP], total cholesterol [TC], triglyceride [TG], and uric acid [UA]) were measured in a sample of 1016 twins between 8 and 17 years of age, recruited from the Qingdao Twin Registry. Cholesky, independent pathway, and common pathway models were used to identify the latent genetic structure behind the clustering of these metabolic traits. Genetic architecture of these metabolic traits was largely similar in boys and girls. The highest heritability was found for BMI (a2 = 0.63) in boys and TC (a2 = .69) in girls. Three heritable factors, adiposity (BMI and WC), blood pressure (SBP and DBP), and metabolite factors (TC, TG, and UA), which formed one higher-order latent phenotype, were identified. Latent genetic, common environmental, and unique environmental factors indirectly impacted the three factors through one single latent factor. Our results suggest that there is one latent factor influencing several metabolic traits, which are known risk factors of CVDs in young Chinese twins. Latent genetic, common environmental, and unique environmental factors indirectly imposed on them. These results inform strategies for gene pleiotropic discovery and intervening of CVD risk factors during childhood and adolescence.
Subject(s)
Cardiovascular Diseases , Heart Disease Risk Factors , Adolescent , Blood Pressure , Body Mass Index , Cardiovascular Diseases/genetics , Child , China , Cluster Analysis , Female , Humans , Male , Risk Factors , Waist CircumferenceABSTRACT
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Subject(s)
Academic Success , Models, Genetic , Twins, Dizygotic , Twins, Monozygotic , Cohort Studies , Female , Humans , Male , Socioeconomic FactorsABSTRACT
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
Subject(s)
Birth Order , Body Height/genetics , Body Mass Index , Pregnancy, Twin/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Pregnancy , Twins, Dizygotic , Twins, MonozygoticABSTRACT
BACKGROUND: the genetic and environmental contributions to cognitive function in the old people have been well addressed for the Western populations using twin modelling showing moderate to high heritability. No similar study has been conducted in the world largest and rapidly ageing Chinese population living under distinct environmental condition as the Western populations. OBJECTIVE: this study aims to explore the genetic and environmental impact on normal cognitive ageing in the Chinese twins. DESIGN/SETTING: cognitive function was measured on 384 complete twin pairs with median age of 50 years for seven cognitive measurements including visuospatial, linguistic skills, naming, memory, attention, abstraction and orientation abilities. Data were analysed by fitting univariate and bivariate twin models to estimate the genetic and environmental components in the variance and co-variance of the cognitive assessments. RESULTS: intra-pair correlation on cognitive measurements was low to moderate in monozygotic twins (0.23-0.41, overall 0.42) and low in dizygotic twins (0.05-0.30, overall 0.31) with the former higher than the latter for each item. Estimate for heritability was moderate for overall cognitive function (0.44, 95% CI: 0.34-0.53) and low to moderate for visuospatial, naming, attention and orientation abilities ranging from 0.28 to 0.38. No genetic contribution was estimated to linguistic skill, abstraction and memory which instead were under low to moderate control by shared environmental factors accounting for 23-33% of the total variances. In contrast, all cognitive performances showed moderate to high influences by the unique environmental factors. CONCLUSIONS: genetic factor and common family environment have a limited contribution to cognitive function in the Chinese adults. Individual unique environment is likely to play a major role in determining the levels of cognitive performance.
Subject(s)
Aging/genetics , Cognition/physiology , Gene-Environment Interaction , Twins/statistics & numerical data , Adult , Aged , Aged, 80 and over , Aging/physiology , Aging/psychology , China/epidemiology , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Twins/genetics , Twins/psychology , Twins, Dizygotic/statistics & numerical data , Twins, Monozygotic/statistics & numerical dataABSTRACT
The genetic influences on aging-related phenotypes, including cognition and depression, have been well confirmed in the Western populations. We performed the first twin-based analysis on cognitive performance, memory and depression status in middle-aged and elderly Chinese twins, representing the world's largest and most rapidly aging population. The sample consisted of 384 twin pairs with a median age of 50 years. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) scale; memory was assessed using the revised Wechsler Adult Intelligence scale; depression symptomatology was evaluated by the self-reported 30-item Geriatric Depression (GDS-30)scale. Both univariate and multivariate twin models were fitted to the three phenotypes with full and nested models and compared to select the best fitting models. Univariate analysis showed moderate-to-high genetic influences with heritability 0.44 for cognition and 0.56 for memory. Multivariate analysis by the reduced Cholesky model estimated significant genetic (rG = 0.69) and unique environmental (rE = 0.25) correlation between cognitive ability and memory. The model also estimated weak but significant inverse genetic correlation for depression with cognition (-0.31) and memory (-0.28). No significant unique environmental correlation was found for depression with other two phenotypes. In conclusion, there can be a common genetic architecture for cognitive ability and memory that weakly correlates with depression symptomatology, but in the opposite direction.
Subject(s)
Aging/genetics , Asian People/genetics , Cognition , Depression/genetics , Diseases in Twins/genetics , Memory , Twins, Dizygotic/genetics , Twins, Monozygotic/genetics , Aged , Aging/psychology , China/epidemiology , Cognition Disorders/epidemiology , Cognition Disorders/genetics , Depression/epidemiology , Depressive Disorder/epidemiology , Depressive Disorder/genetics , Diseases in Twins/epidemiology , Female , Gene-Environment Interaction , Humans , Intelligence/genetics , Male , Memory Disorders/epidemiology , Memory Disorders/genetics , Middle Aged , Models, Genetic , Multivariate Analysis , Phenotype , Psychological Tests , RegistriesABSTRACT
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
Subject(s)
Anthropometry , Body Height/genetics , Body Mass Index , Body Weight/genetics , Gene-Environment Interaction , Twins/genetics , Female , Humans , Male , Phenotype , Twin Studies as TopicABSTRACT
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
Subject(s)
Body Height , Body Mass Index , Twins, Dizygotic , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cohort Studies , Databases, Factual , Female , Humans , Infant , Linear Models , Male , Middle Aged , Twins, Monozygotic , Young AdultABSTRACT
We evaluated the genetic and environmental contributions to metabolic cardiovascular risk factors and their mutual associations. Eight metabolic factors (body mass index, waist circumference, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, total serum cholesterol, serum triglycerides, and serum uric acid) were measured in 508 twin pairs aged 8-17 years from the Qingdao Twin Registry, China. Linear structural equation models were used to estimate the heritability of these traits, as well as the genetic and environmental correlations between them. Among boys, body mass index and uric acid showed consistently high heritability (0.49-0.81), whereas other traits showed moderate to high common environmental variance (0.37-0.73) in children (8-12 years) and adolescents (13-17 years) except total cholesterol. For girls, moderate to high heritability (0.39-0.75) were obtained for six metabolic traits in children, while only two traits showed high heritability and others mostly medium to large common environmental variance in adolescents. Genetic correlations between the traits were strong in both boys and girls in children (r g = 0.64-0.99 between body mass index and diastolic blood pressure; r g = 0.71-1.00 between body mass index and waist circumference), but decreased for adolescent girls (r g = 0.51 between body mass index and waist-to-hip ratio; r g = 0.55 between body mass index and uric acid; r g = 0.61 between body mass index and systolic blood pressure). The effect of genetic factors on most metabolic traits decreased from childhood to adolescence. Both common genetic and specific environmental factors influence the mutual associations among most of the metabolic traits.
Subject(s)
Asian People/genetics , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/genetics , Twins/genetics , Adolescent , Chi-Square Distribution , Child , China/epidemiology , Cohort Studies , Female , Genetic Predisposition to Disease , Humans , Male , Risk FactorsABSTRACT
OBJECTIVE: To explore the occupational and reproductive health problems of migrant female workers in electron factory. METHODS: A total number of 2000 female migrant workers were randomly sampled from three electronic factories for the study. All were investigated by questionnaire and data were input to EpiData 3.0 data base, SPSS17.0 statistical software and analyzed by Chi-square test. RESULTS: 1971 complete questionnaires were received, the recovery rate reached over 98.6%. The average age of interviewees is (21.1 ± 3.9) years. Junior employee between 16 and 18 years accounted for 19.04%. The average working age was (1.1 ± 2.2) years and about 90% were single including 0.11% of them were divorced. The main occupational hazards were: sodium hydroxide, sodium carbonate, formaldehyde, hydrochloric acid, stannic anhydride, benzene analogues, n-hexane methanol, glycol isopropanol, sulphuric acid, nitric oxide, noise, ultraviolet radiation, etc. Workplace monitoring indicated that benzene and noise levels and ultraviolet radiation were over the national OEL at fewer worksites. More than 50% female workers worked over 8 hours per day and 83% of them worked 22 days per month. The ergonomic problems: 63.86% of them worked with tedious repetitiveness and monotonous job task. About 42% of them need to be continuously with standing posture. As a consequence, there were 30% workers complain about LBP, 21% had experienced work injury; 15% â¼ 18% had some non-specific discomfort, such as insomnia, dysacusis, dizzy and headache. The incidence rate of reproductive system such as abnormal menstrual cycle (5.71%), dysmenorrhea (25.11%), congestion (8.91%), etc. The first four reproductive system disease were pelvic inflammation, adnexitis, cervical erosion, and vaginitis. There are significant differences between continuous and temporary standing work, and repeated and unrepeated job action in terms of dysmenorrheal and congestion related-discomfort(P < 0.05). CONCLUSION: There are many occupational hazards in electronic industry. And there is somewhat a serious occupational and reproductive health problems among female migrant workers, that seem to be a matter of great concern.
Subject(s)
Health Status , Occupational Health , Reproductive Health , Transients and Migrants , Adolescent , Adult , Female , Humans , Industry , Occupational Exposure , Surveys and Questionnaires , Workplace , Young AdultABSTRACT
Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis.
Subject(s)
Body Height , Environment , Gene-Environment Interaction , Genetic Background , Parenting , Parents , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Parents/education , Quantitative Trait Loci , Quantitative Trait, Heritable , Young AdultABSTRACT
OBJECTIVE: The objective of this study was to analyze how parental education modifies the genetic and environmental variances of BMI from infancy to old age in three geographic-cultural regions. METHODS: A pooled sample of 29 cohorts including 143,499 twin individuals with information on parental education and BMI from age 1 to 79 years (299,201 BMI measures) was analyzed by genetic twin modeling. RESULTS: Until 4 years of age, parental education was not consistently associated with BMI. Thereafter, higher parental education level was associated with lower BMI in males and females. Total and additive genetic variances of BMI were smaller in the offspring of highly educated parents than in those whose parents had low education levels. Especially in North American and Australian children, environmental factors shared by co-twins also contributed to the higher BMI variation in the low education level category. In Europe and East Asia, the associations of parental education with mean BMI and BMI variance were weaker than in North America and Australia. CONCLUSIONS: Lower parental education level is associated with higher mean BMI and larger genetic variance of BMI after early childhood, especially in the obesogenic macro-environment. The interplay among genetic predisposition, childhood social environment, and macro-social context is important for socioeconomic differences in BMI.
Subject(s)
Body Mass Index , Gene-Environment Interaction , Parents/education , Adolescent , Adult , Aged , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Male , Middle Aged , Twins , Young AdultABSTRACT
It is well established that boys are born heavier and longer than girls, but it remains unclear whether birth size in twins is affected by the sex of their co-twin. We conducted an individual-based pooled analysis of 21 twin cohorts in 15 countries derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), including 67,850 dizygotic twin individuals. Linear regression analyses showed that boys having a co-twin sister were, on average, 31 g (95% CI 18 to 45) heavier and 0.16 cm (95% CI 0.045 to 0.274) longer than those with a co-twin brother. In girls, birth size was not associated (5 g birth weight; 95% CI -8 to -18 and -0.089 cm birth length; 95% CI -0.202 to 0.025) with the sex of the co-twin. Gestational age was slightly shorter in boy-boy pairs than in boy-girl and girl-girl pairs. When birth size was standardized by gestational age, the magnitude of the associations was attenuated in boys, particularly for birth weight. In conclusion, boys with a co-twin sister are heavier and longer at birth than those with a co-twin brother. However, these differences are modest and partly explained by a longer gestation in the presence of a co-twin sister.
Subject(s)
Birth Weight , Body Height , Gestational Age , Twins, Dizygotic , Cohort Studies , Female , Humans , MaleABSTRACT
Background: The genetic architecture of birth size may differ geographically and over time. We examined differences in the genetic and environmental contributions to birthweight, length and ponderal index (PI) across geographical-cultural regions (Europe, North America and Australia, and East Asia) and across birth cohorts, and how gestational age modifies these effects. Methods: Data from 26 twin cohorts in 16 countries including 57 613 monozygotic and dizygotic twin pairs were pooled. Genetic and environmental variations of birth size were estimated using genetic structural equation modelling. Results: The variance of birthweight and length was predominantly explained by shared environmental factors, whereas the variance of PI was explained both by shared and unique environmental factors. Genetic variance contributing to birth size was small. Adjusting for gestational age decreased the proportions of shared environmental variance and increased the propositions of unique environmental variance. Genetic variance was similar in the geographical-cultural regions, but shared environmental variance was smaller in East Asia than in Europe and North America and Australia. The total variance and shared environmental variance of birth length and PI were greater from the birth cohort 1990-99 onwards compared with the birth cohorts from 1970-79 to 1980-89. Conclusions: The contribution of genetic factors to birth size is smaller than that of shared environmental factors, which is partly explained by gestational age. Shared environmental variances of birth length and PI were greater in the latest birth cohorts and differed also across geographical-cultural regions. Shared environmental factors are important when explaining differences in the variation of birth size globally and over time.
Subject(s)
Birth Weight , Body Height , Environment , Growth , Female , Gene-Environment Interaction , Geography , Humans , Internationality , Male , Twins, Dizygotic , Twins, MonozygoticABSTRACT
BACKGROUND AND OBJECTIVES: Fruit, vegetable, seafood, and dairy intake may reduce the risk of type 2 diabetes, but this relationship is unclear. We aimed to examine the associations between fruit, vegetable, seafood, and dairy intake and type 2 diabetes prevalence in a Chinese population. METHODS AND STUDY DESIGN: A total of 4,343 individuals aged 35-74 years participated in a population-based cross-sectional study in Qingdao, China. The frequency and quantity of fruit, vegetable, seafood, and dairy intake were determined using a standard food frequency questionnaire. Diabetes was classified according to the WHO/IDF 2006 criteria. Logistic regression analysis was employed to estimate odds ratio (OR) for type 2 diabetes in relation to fruit, vegetable, seafood, and dairy intake in a multivariable model. RESULTS: The multivariate-adjusted ORs (95% confidence interval) for the presence of type 2 diabetes were 0.68 (0.46-0.98), 0.50 (0.37-0.68), and 0.91 (0.66-1.25), respectively, for the highest versus the lowest groups regarding total fruit and vegetable, fruit or vegetable intake in women. The ORs for type 2 diabetes prevalence regarding the quantity of fruit and vegetable, fruit, and yogurt intake were 0.88 (0.78-0.99), 0.71 (0.61-0.82), and 0.56 (0.32-0.98) in women, but not in men. Seafood consumption was inversely associated with diabetes risk in men, but not in women; the corresponding figures were 0.58 (0.35-0.96) and 0.92 (0.63-1.36), respectively. CONCLUSIONS: Fruit, vegetable, and yogurt intake in women and seafood intake in men were inversely associated with type 2 diabetes prevalence in this Chinese population. These findings require confirmation in a prospective study.
Subject(s)
Dairy Products , Diabetes Mellitus, Type 2/epidemiology , Diet , Fruit , Seafood , Vegetables , Adult , Aged , China/epidemiology , Cross-Sectional Studies , Diabetes Mellitus, Type 2/prevention & control , Diet Surveys , Female , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Sex Factors , YogurtABSTRACT
BACKGROUND: Both genetic and environmental factors are known to affect body mass index (BMI), but detailed understanding of how their effects differ during childhood and adolescence is lacking. OBJECTIVES: We analyzed the genetic and environmental contributions to BMI variation from infancy to early adulthood and the ways they differ by sex and geographic regions representing high (North America and Australia), moderate (Europe), and low levels (East Asia) of obesogenic environments. DESIGN: Data were available for 87,782 complete twin pairs from 0.5 to 19.5 y of age from 45 cohorts. Analyses were based on 383,092 BMI measurements. Variation in BMI was decomposed into genetic and environmental components through genetic structural equation modeling. RESULTS: The variance of BMI increased from 5 y of age along with increasing mean BMI. The proportion of BMI variation explained by additive genetic factors was lowest at 4 y of age in boys (a(2) = 0.42) and girls (a(2) = 0.41) and then generally increased to 0.75 in both sexes at 19 y of age. This was because of a stronger influence of environmental factors shared by co-twins in midchildhood. After 15 y of age, the effect of shared environment was not observed. The sex-specific expression of genetic factors was seen in infancy but was most prominent at 13 y of age and older. The variance of BMI was highest in North America and Australia and lowest in East Asia, but the relative proportion of genetic variation to total variation remained roughly similar across different regions. CONCLUSIONS: Environmental factors shared by co-twins affect BMI in childhood, but little evidence for their contribution was found in late adolescence. Our results suggest that genetic factors play a major role in the variation of BMI in adolescence among populations of different ethnicities exposed to different environmental factors related to obesity.
Subject(s)
Body Mass Index , Environment , Gene-Environment Interaction , Genetic Variation , Obesity/etiology , Twins, Dizygotic/genetics , Twins, Monozygotic/genetics , Adolescent , Adult , Age Factors , Australia , Child , Child, Preschool , Europe , Asia, Eastern , Female , Humans , Infant , Male , North America , Obesity/ethnology , Obesity/genetics , Sex Factors , Young AdultABSTRACT
Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1-19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia, and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments.