[Analysis on the heritability of diabetes, based on data from the Chinese adult twins].

Objective: To analyze the heritability of diabetes among the Chinese twin adults. Methods: A total of 10 253 same-sex twin pairs aged 25 years and older, were selected from the Chinese National Twin Registry (CNTR) program. Heritability of diabetes was calculated by using the structural equation model. Results: After adjusted for age and gender, the overall heritability rates of diabetes were 0.41 (0.15-0.75), 0.83 (0.72-0.91) and 0.34 (0.04-0.73) in the <45 and ≥45 years twin pairs, respectively. After adjusted for age, rates of heritability appeared as 0.37 (0.05-0.78) and 0.88 (0.79-0.94) in men and women, respectively. Conclusions: Diabetes is affected by both genetic and environmental factors. The genetic effect of diabetes seemed stronger on female than that on male twins but was dying down along with ageing.

[The Wuhan Twin Birth Cohort Study].

The prevalence of child and adolescent growth and mental-behavior related diseases are increasing, and the pathogenesis are complex. Twins are excellent natural resources for complex chronic diseases research as they share the maternal intrauterine environment, born at the same time and share the same family environment in early years, which could benefit the adjust ment of confounding factors, such as age, genetic factors and early family environmental factors. Birth cohort with twin families involved could be more effective in exploring the genetic and environmental factors for complex chronic diseases at the very beginning of life. This paper summarizes the objective, content, progress, strengths and potential problems of Wuhan Twin Birth Cohort, with emphasis on the overall design and progress of the study.

[The Chinese national twin cohort: an update].

The importance of large cohort studies in China has been increasingly emphasized. As special group in the population, twins provide excellent natural resources since they share the same birthday, maternal intrauterine environment and early family environment. Twin cohorts are unique for and benefit on controlling the confounding factors as age, gender (same-sex twins), genetic background (monozygotic twins) or early environment (being raised together) in the etiological studies on complex diseases. In this review, we briefly introduce the objectives, current situation, challenges and opportunities related to the Chinese national twin cohort, focusing on the characteristics of twins that are different from other groups in the general population.

Genetic and Environmental Influences on the Mental Health of Children: A Twin Study.

The current study explored the influences of genetic and environmental factors on the mental health of twins between ages 6 and 16. A total of 41 monozygotic (MZ) twins and 35 dizygotic twins were recruited. The psychological attributes and environmental information of children were evaluated. A significant correlation was found between twins in the diagnostic categories of any psychiatric disorder and attention deficit/hyperactivity disorder (ADHD)/hyperkinesis based on the Strengths and Difficulties Questionnaire scale in MZ twins. Furthermore, fathers' authoritarian parenting style was positively correlated with the probability of any psychiatric disorders and oppositional/conduct disorders, whereas mothers' authoritative parenting style was negatively correlated with the probability of any psychiatric disorders and ADHD/hyperkinesis. The probability of emotional disorders was negatively correlated with scores on the Stressful Life Events Scale. These results collectively suggest that genetic and environmental elements, such as parental rearing style and stressful life events, may influence children's mental health. [Journal of Psychosocial Nursing and Mental Health Services, 54(8), 29-34.].

JAGGED1 gene variations in Chinese twin sisters with Alagille syndrome.

Variations in the JAGGED1 gene have been found to cause Alagille syndrome. Nevertheless, no particular hotspots in the gene have been found; any part of the entire coding regions for JAGGED1 may be involved. Twin sisters with jaundice visited our hospital and were diagnosed with Alagille syndrome. The gene variations in their JAGGED1 coding sequences were evaluated by complementary DNA sequencing. The 12-month-old twin sisters have broad foreheads, deep-set eyes, pointed chins, and triangular faces with jaundice. Clinical testing showed the presence of posterior embryotoxon, butterfly vertebrae, and atrial septal defect. Biochemical indexes showed cholestasis and liver damage. Three conserved variations were identified within exons 22 (c.2612C>G), 24 (c.2957T>A), and 26 (c.3417T>C) in the JAGGED1 coding sequence. The predicted consequences for c.2612C>G, c.2957T>A, and c.3417T>C were p.Pro871Arg, p.Leu986*, and p.Tyr1139=, respectively. The T to A change in the JAGGED1 coding sequence at 2957 will generate a stop codon and might lead to deletion of amino acid 233 at the C terminal of the JAGGED1 protein. Our data suggest that gene variations of c.2612C>G, c.2957T>A, and c.3417T>C, especially c.2957T>A, might have contributed to the pathogenesis of Alagille syndrome in these Chinese twin sisters and provided new gene evidences for Alagille syndrome.

Telomere shortening as genetic risk factor of liver cirrhosis.

Cirrhosis is the main complication of chronic liver disease, leads to progressive liver function impairment and is the main risk factor for the development of liver cancer. Liver failure at endstage cirrhosis is associated with increased mortality with liver transplantation as the only possible treatment at this stage. The pathogenesis of liver cirrhosis is not completely elucidated. Although the common factors leading to liver injury, such as viral hepatitis, alcohol consume or fatty liver disease can be identified in the majority of patients a small percentage of patients have no apparent risk factors. Moreover given the same risk factors, some patients progress to cirrhosis whereas others have a benign course, the reason remains unclear. In order to develop new diagnostic and therapeutic tools, it is s essential to understand the pathogenesis of cirrhosis. The identification of genetic risk factors associated with cirrhosis is one of the possible approach to achieve these goal. In the past years several studies have supported the role of telomere shortening and cirrhosis. In the recent year several studies on the relation between several single nucleotide polymorphism (SNPs) and cirrhosis have been published; it has been proposed also a cirrhosis risk score based on seven SNPs. Also epidemiological studies on identical twins and in different ethnic groups have been supporting the importance of the role of genetic risk factors. Finally in the very recent years it has been suggested that telomere shortening may represent a genetic risk factor for the development of cirrhosis.

Are there common familial influences for major depressive disorder and an overeating-binge eating dimension in both European American and African American female twins?

OBJECTIVE: Although prior studies have demonstrated that depression is associated with an overeating-binge eating dimension (OE-BE) phenotypically, little research has investigated whether familial factors contribute to the co-occurrence of these phenotypes, especially in community samples with multiple racial/ethnic groups. We examined the extent to which familial (i.e., genetic and shared environmental) influences overlapped between Major Depressive Disorder (MDD) and OE-BE in a population-based sample and whether these influences were similar across racial/ethnic groups. METHOD: Participants included 3,226 European American (EA) and 550 African American (AA) young adult women from the Missouri Adolescent Female Twin Study. An adaptation of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was administered to assess lifetime DSM-IV MDD and OE-BE. Quantitative genetic modeling was used to estimate familial influences between both phenotypes; all models controlled for age. RESULTS: The best-fitting model, which combined racial/ethnic groups, found that additive genetic influences accounted for 44% (95% CI: 34%, 53%) of the MDD variance and 40% (25%, 54%) for OE-BE, with the remaining variances due to non-shared environmental influences. Genetic overlap was substantial (rg = .61 [.39, .85]); non-shared environmental influences on MDD and OE-BE overlapped weakly (re = .26 [.09, .42]). DISCUSSION: Results suggest that common familial influences underlie MDD and OE-BE, and the magnitude of familial influences contributing to the comorbidity between MDD and OE-BE is similar between EA and AA women. If racial/ethnic differences truly exist, then larger sample sizes may be needed to fully elucidate familial risk for comorbid MDD and OE-BE across these groups.

Differences in risk factors for retinopathy of prematurity development in paired twins: a Chinese population study.

PURPOSE: To determine the differences in risk factors for retinopathy of prematurity (ROP) in paired twins. METHODS: A retrospective medical record review was performed for all paired twins screened for ROP between 2007 and 2012. Screening was offered to very low birth weight (≤ 1500 grams) and preterm (≤ 32 weeks) neonates. Twins 1 and 2 were categorized based on the order of delivery. Maternal and neonatal covariates were analyzed using univariate and multivariate regression analyses for both ROP and Type 1 ROP. RESULTS: In 34 pairs of Chinese twins, the mean gestational age (GA) was 30.2 ± 2.0 weeks. In Twin 1, smaller GA (OR = 0.44, P = 0.02), higher mean oxygen concentration (OR = 1.34, P = 0.03), presence of thrombocytopenia (OR = 1429.60, P < 0.0001), and intraventricular hemorrhage (OR = 18.67, P = 0.03) were significant risk factors for ROP. For Twin 2, a smaller GA (OR = 0.45, P = 0.03) was the only risk factor. There were no significant risk factors for ROP in Twin 1 or Twin 2 on multivariate analysis. CONCLUSION: In Chinese twin pairs, smaller GA was the only common risk factor for ROP while Twin 1 was more susceptible to the postnatal risks for ROP.

Imputing observed blood pressure for antihypertensive treatment: impact on population and genetic analyses.

BACKGROUND: Elevated blood pressure (BP), a heritable risk factor for many age-related disorders, is commonly investigated in population and genetic studies, but antihypertensive use can confound study results. Routine methods to adjust for antihypertensives may not sufficiently account for newer treatment protocols (i.e., combination or multiple drug therapy) found in contemporary cohorts. METHODS: We refined an existing method to impute unmedicated BP in individuals on antihypertensives by incorporating new treatment trends. We assessed BP and antihypertensive use in male twins (n = 1,237) from the Vietnam Era Twin Study of Aging: 36% reported antihypertensive use; 52% of those treated were on multiple drugs. RESULTS: Estimated heritability was 0.43 (95% confidence interval (CI) = 0.20-0.50) and 0.44 (95% CI = 0.22-0.61) for measured systolic BP (SBP) and diastolic BP (DBP), respectively. We imputed BP for antihypertensives by 3 approaches: (i) addition of a fixed value of 10/5mm Hg to measured SBP/DBP; (ii) incremented addition of mm Hg to BP based on number of medications; and (iii) a refined approach adding mm Hg based on antihypertensive drug class and ethnicity. The imputations did not significantly affect estimated heritability of BP. However, use of our most refined imputation method and other methods resulted in significantly increased phenotypic correlations between BP and body mass index, a trait known to be correlated with BP. CONCLUSIONS: This study highlights the potential usefulness of applying a representative adjustment for medication use, such as by considering drug class, ethnicity, and the combination of drugs when assessing the relationship between BP and risk factors.

Heritability of eleven metabolic phenotypes in Danish and Chinese twins: a cross-population comparison.

OBJECTIVES: A twin-based comparative study on the genetic influences in metabolic endophenotypes in two populations of substantial ethnic, environmental, and cultural differences was performed. DESIGN AND METHODS: Data on 11 metabolic phenotypes including anthropometric measures, blood glucose, and lipids levels as well as blood pressure were available from 756 pairs of Danish twins (309 monozygotic and 447 dizygotic twin pairs) with a mean age of 38 years (range: 18-67) and from 325 pairs of Chinese twins (183 monozygotic and 142 dizygotic twin pairs) with a mean age of 40.5 years (range: 18-69). Twin modeling was performed on full and nested models with the best fitting models selected. RESULTS: Heritability estimates were compared between Danish and Chinese samples to identify differential genetic influences on each of the phenotypes. Except for hip circumference, all other body measures exhibited similar heritability patterns in the two samples with body weight showing only a slight difference. Higher genetic influences were estimated for fasting blood glucose level in Chinese twins, whereas the Danish twins showed more genetic regulation over most lipids phenotypes. Systolic blood pressure was more genetically controlled in Danish than in Chinese twins. CONCLUSIONS: Metabolic endophenotypes show disparity in their genetic determinants in populations under distinct environmental conditions.

Heritability of arthritis in African American twins: findings from the Carolina African American Twins Study of Aging.

PURPOSE: To determine the genetic and environmental influences exerted on arthritis by measuring the distribution of self-reported arthritis diagnoses among monozygotic (MZ) and dizygotic (DZ) African American twins. METHODS: A cross-sectional study was conducted on 97 MZ and 113 DZ twin pairs recruited into the Carolina African American Twin Study of Aging (CAATSA). The sample had a mean age of 47 +/- 13.9 years. A twin design was used to determine correlations in arthritis diagnosis for MZ and DZ twins and to estimate the contribution of genes and environment to the variation in an arthritis diagnosis. RESULTS: The concordance rate for being diagnosed with arthritis was 42% for MZ twins, and 20% for DZ twins, resulting in a 2.1:1 ratio of MZ to DZ concordance. These results indicate a significant proportion of individual variability was due to genetic factors (43%) on an arthritis diagnosis as well as 57% of variance due to nonshared environmental influences. CONCLUSION: This research suggests that while there are genetic influences on arthritis diagnosis, environmental factors, such as infections, dietary factors, urbanization, and pollutants, also play a role in accounting for variability in the diagnosis and treatment of arthritis among diverse populations.

A family report of Crohn's disease in three children immigrating from Albania to Greece and review of the literature.

Cases of immigrant families affected by IBD have rarely been reported and seem to be of exceptional interest towards a better understanding of disease aetiopathogenesis. The first case of Crohn's disease in a family of immigrants from Albania to Greece with three offspring is described herein. A family with three children, one 22 year-old male and two 18-year-old twin females immigrated from southern Albania to northwest Greece ten years ago. The whole family lived in the same house and had no previous history of bowel or other chronic diseases. Two years ago the boy complained of diarrhoea, perianal pain and loss of weight. Subsequent investigation revealed ileal and perianal Crohn's disease. One year after Crohn's disease was diagnosed in the boy, one of the twins was diagnosed with ileal Crohn's disease. Six months afterwards, the second twin underwent emergency appendectomy due to acute appendicitis; four months later she was diagnosed with ileal Crohn's disease. Genetically predisposed individuals seem to be vulnerable to a continuous pressure of a still unknown environmental factor(s). In addition, lifestyle modification seems to represent a predisposing factor toward inflammatory bowel disease in immigrants.

Epidemiology and symptomatology of depression in Sri Lanka: a cross-sectional population-based survey in Colombo District.

BACKGROUND: It is important to understand the nature of depression in non-Western and lower-income countries, but little such research exists. This study aimed to examine the characteristic features of depression in Sri Lanka, and to identify environmental risk factors. METHODS: Depression diagnoses, symptoms and impairment were measured using the Composite International Diagnostic Interview, in a population-based sample of 6014 twins and non-twins in the Colombo region of Sri Lanka (the CoTASS sample). Socio-demographic factors and environments were assessed via questionnaires. RESULTS: Lifetime-ever depression was reported in 6.6% of participants, rising to 11.2% if the functional impairment criterion was excluded. The symptom profile of depression and its socio-demographic associations were very comparable to those in Western and more economically developed countries, whether functional impairment was included in the definition or not. Standard of living was independently associated with depression, especially among men at the more deprived end of the distribution. Specific associations were found with both financial wellbeing and material characteristics of the home environment. LIMITATIONS: The observational associations identified are cross-sectional, so do not necessarily imply causal links. CONCLUSIONS: Aside from a lower prevalence, depression is very similar in this predominantly urban Sri Lankan sample to higher-income, Western countries, and may be under-identified due to a relatively low cultural appropriateness of the assessment of impairment. Under Sri Lanka's cultural and environmental context, certain aspects of the material environment are associated with depression among certain segments of society, perhaps because of their particular link to social status and social networks.

Concordance rates for cognitive impairment among older African American twins.

BACKGROUND: There is significant attention to the growing elderly African American population and estimating who and how many within this population will be affected by cognitive impairment. OBJECTIVE: The etiology of cognitive impairment has not been well studied in African Americans and the contribution of genetic and environmental influences to cognitive impairment is not clear. METHODS: We calculated concordance rates and heritability for cognitive impairment in 95 same-sexed pairs of African American twins from the Carolina African American Twin Study on Aging (CAATSA). The sample had an average age of 59.6 years (SD = 8.6 years, range 50-88 years) and 60% were female. The Telephone Interview for Cognitive Status (TICS) was used to assess cognitive impairment with a lower cutoff based on our previous research with African Americans. RESULTS: Thirteen of the monozygotic (MZ) twins (30.2%) and 9 of the dizygotic (DZ) twins (17.3%) were cognitively impaired. The concordance rate was 72% for MZ and 45% for DZ. We found the heritability for cognitive impairment to be 54%. CONCLUSIONS: The study findings indicate that cognitive impairment is highly heritable, suggesting that genetics may play a relatively large role in the development of cognitive impairment in African American twins.

Role of genetic factors in lower- and higher-order aberrations--the genes in myopia twin study.

AIMS: We intended to investigate the relative genetic contribution in wavefront aberrations using a sub-group of twins recruited in the Genes in Myopia twin study, and subsequently provide direction for future studies into the aetiology of mono-chromatic aberrations. To our knowledge, the Genes in Myopia twin study is the first study to explore the role of genetic factors in both lower- and higher-order aberrations in a Caucasian population. METHODS: Each individual completed a general questionnaire and underwent a comprehensive eye examination. Higher-order wavefront aberrations were calculated with Zernike coefficients up to the fourth order. RESULTS: A total of 46 twin pairs with a mean age of 65.3 years were included in the analysis. Monozygotic intra-pair correlations were significantly higher compared to those in dizygotic twin pairs for defocus aberrations (p < 0.05). A trend for a genetic component was identified for higher-order aberrations. CONCLUSION: Genetic studies into refraction typically explore the genetic effects of lower-order aberrations such as myopia and hypermetropia; however, there is little to no research into the genetic basis of higher-order aberrations. The Genes in Myopia twin study indicates a potential genetic role for higher-order aberrations and provides useful insights into the aetiology of refractive error.

Eating behaviour and weight in children.

OBJECTIVE: To test the hypothesis that quantitative variation in eating behaviour traits shows a graded association with weight in children. DESIGN: Cross-sectional design in a community setting. SUBJECTS: Data were from 406 families participating in the Physical Exercise and Appetite in CHildren Study (PEACHES) or the Twins Early Development Study (TEDS). Children were aged 7-9 years (PEACHES) and 9-12 years (TEDS). MEASUREMENTS: Weights and heights were measured by researchers. Body mass index (BMI) s.d. scores were used to categorize participants into underweight, healthy weight, overweight and obese groups, with an additional division of the healthy weight group into higher and lower healthy weight at the 50th centile. Eating behaviour traits were assessed with the Child Eating Behaviour Questionnaire (CEBQ), completed by the parents on behalf of their child. Linear trend analyses compared CEBQ subscale scores across the five weight groups. RESULTS: Satiety Responsiveness/Slowness in Eating and Food Fussiness showed a graded negative association with weight, whereas Food Responsiveness, Enjoyment of Food, Emotional Overeating and Desire to Drink were positively associated. All effects were maintained after controlling for age, sex, ethnicity, parental education and sample. There was no systematic association with weight for Emotional Undereating. CONCLUSION: These results support the idea that approach-related and avoidance-related appetitive traits are systematically (and oppositely) related to adiposity, and not exclusively associated with obesity. Early assessment of these traits could be used as indicators of susceptibility to weight gain.

Depressive symptoms and cigarette smoking in twins from the National Longitudinal Study of Adolescent Health.

OBJECTIVE: To our knowledge, no prior twin studies have examined genetic and environmental contributions to the association of depressive symptoms and cigarette smoking in adolescence. DESIGN: Genetic and environmental contributions to the covariation of depressive symptoms and cigarette smoking were estimated among 287 monozygotic and 441 dizygotic adolescent twin pairs from the National Longitudinal Study of Adolescent Health. MAIN OUTCOME MEASURES: Depressive symptoms were measured using an 18-item modified version of the Center for Epidemiologic Studies-Depression Scale (CES-D; Radloff, 1977). Smoking involvement was defined using an ordinal scale based on smoking recency and frequency. RESULTS: Depressive symptoms and smoking were significantly correlated in both males and females. Twin modeling indicated that, in females, the correlation was attributable in part to common genetic factors and in part to environmental factors not shared among twins, or nonshared environment. In males, the correlation between depressive symptoms and smoking was solely attributable to nonshared environment. CONCLUSIONS: Nonshared environmental correlations in males and females lend support to a direct causal relationship between depressive symptoms and smoking in adolescence. However, the additional common genetic vulnerability in females suggested that common genetic factors also contribute, particularly among adolescent females.

Racial disparity in fetal growth inhibition among singletons and multiples.

OBJECTIVE: The purpose of this study was to determine the magnitude of black-white gap in intrauterine fetal growth inhibition among singletons and multiples. STUDY DESIGN: This was a cross-sectional study on singleton, twin, and triplet live births in the United States from 1995 through 1998. We compared the risk for low and very low-birth-weight, preterm and very preterm, and small-for-gestational age between black and white neonates. RESULTS: A total of 14,245,865 singletons (blacks = 16.2%), 392,761 twins (blacks = 18.0%), and 21,436 triplets (blacks = 7.7%) were analyzed. Black neonates depicted significantly higher risks for all indices of fetal growth inhibition regardless of plurality. The gestational age of onset of fetal growth lag for black fetuses was earliest among triplets (23 weeks and the gap remained unchanged) then singletons (26 weeks; maximum gap 37-42 weeks), and finally twins (33 weeks; maximum gap 37-40 weeks). CONCLUSION: Black-white disparity in fetal growth inhibition varied by plurality subtypes. The different gestational ages of onset of black-white fetal growth divergence could potentially be exploited for targeting intervention measures aimed at narrowing the gap.

Single motherhood and neonatal survival of twins among blacks and whites.

OBJECTIVE: We investigated whether an association existed between single motherhood and neonatal mortality among twins and whether such a linkage varied by race. STUDY DESIGN: Retrospective cohort analysis on 446,570 twin live births (between 24-44 gestational weeks inclusive) in the United States from 1995 through 1998. Neonatal survival was compared between twins of single and those of married mothers for blacks and whites separately using Cox proportional hazards regression that adjusted for the confounding effects of education, parity, adequacy of prenatal care and maternal smoking during pregnancy. The Robust Sandwich Estimator was employed to adjust for intracluster correlation. RESULTS: The rates for neonatal mortality among blacks were 34.9 per 1,000 among married and 43.4 per 1,000 among single mothers. Among whites, the rates were 20.6 per 1,000 for married and 28.9 per 1,000 for unmarried mothers. Neonatal mortality was significantly elevated among white twins of single mothers (Hazard Ratio (HR) = 1.23; 95% Confidence Interval (CI) = 1.14-1.31) and among black twins of single mothers (HR = 1.12; 95% CI = 1.01-1.25). However, when gestational age was adjusted for, the association between single motherhood and neonatal mortality disappeared. CONCLUSION: Single motherhood was a risk factor for neonatal mortality among twins, and the disparity in survival was more accentuated among whites. The association between single motherhood and neonatal mortality was explained by the preponderance of preterm births among twins of unmarried gravidas. Our findings reinforce the importance of future research to develop and test interventions that will decrease the incidence of preterm birth.