We aimed to assess shared genetic correlations of depressive and anxiety symptoms with concurrent and future estimated cardiovascular risk (CVR) score in Korean twins and family members. For the relationship with Adult Treatment Panel III CVR estimate in subjects aged 30–74 years (n = 1,059, baseline and follow-up after 3.2 ± 1.2 years), Center for Epidemiological Studies Depression Scale (CES-D) and state and trait anxiety inventory (SAI and TAI) were measured at baseline. A mixed linear model for CVR scores at baseline and follow-up was applied to include depressive and anxiety symptoms, twin and family effects, income, education, alcohol use, exercise, body mass index, and baseline CVR score for follow-up analysis. Higher CES-D scores were associated with higher CVR score at baseline in men, while higher TAI score was associated with higher CVR score at follow-up in women. Heritabilities were 0.245~0.326 for CVR score, 0.320 for CES-D score, 0.367 for TAI score, and 0.482 for SAI score. There were significant common genetic correlations in the relationships of CES-D, TAI, and SAI scores with CVR scores at baseline and follow-up (after adjusting for baseline CV risk score). Shared common environmental correlations were observed in the relationships of CES-D and SAI scores with CVR score at baseline; and SAI score with CVR score at follow-up. In the within-monozygotic twin analysis, there were no associations between CES-D, TAI, and SAI scores, and CVR score. In conclusion, shared genetic and environmental influences were observed in the relationship between depressive and anxiety symptoms with concurrent and future CVR estimates.

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.

An accessory navicular bone (AN) is the most common accessory ossicle in the foot. The presence of an AN bone can trigger various foot problems, such as posterior tibial tendon pathology, flattening of the medial longitudinal arch, and medial foot pain. Despite the clinical influence of presence of an AN in foot disease, the research regarding its inheritance is still insufficient. A total of 135 pairs of monozygotic (MZ) twins, 25 pairs of dizygotic (DZ) twins, and 676 singletons from families were enrolled in order to estimate genetic influences on AN. After confirmation of zygosity and family relationship with a tandem repeat marker kit and questionnaires, the presence and type of the AN was classified through bilateral feet radiographic examination. The heritability of an AN was estimated using quantitative genetic analysis based on a variance decomposition model considering various types of family relationships: father–offspring pair, mother–offspring pair, and pooled DZ twin and sibling pairs. As a result, approximately 40.96% of the participants in this study had an AN in either foot, with type II being the most common type. The heritability for the presence of any type of an AN in any foot was estimated as 0.88 (95% CI [0.82, 0.94]) after adjusting for age and sex. Specifically, type II AN showed the highest heritability of 0.82 (95% CI [0.71–0.93]). The high heritability of an AN found in this large twin and family study suggests that an AN is determined by the substantial influence of genetic factor.

Family study can provide estimates of overall genetic influences on a particular trait because family relationships provide accurate measures of average genetic sharing. However, evidence of genetic contributions to skin phenotypes is limited, which may preclude genetic studies to identify genetic variants or to understand underlying molecular biology of skin traits. This study aimed to estimate genetic and environmental contributions to selected dermatologic phenotypes, that is, to melanin index, sebum secretion, and skin humidity level in a Korean twin-family cohort. We investigated more than 2,000 individuals from 486 families, including 388 monozygotic twin pairs and 82 dizygotic twin pairs. Variance component method was used to estimate genetic influences in terms of heritability. Heritability of skin melanin index, sebum secretion, and skin humidity (arm and cheek) were estimated to be 0.44 [95% CI 0.38–0.49], 0.21 [95% CI 0.16–0.26], 0.13 [95% CI 0.07–0.18], and 0.11 [95% CI 0.06–0.16] respectively, after adjusting for confounding factors. Our findings suggest that genetics play a major role on skin melanin index, but only mild roles on sebum secretion and humidity. Sebum secretion and skin humidity are controlled predominantly by environmental factors notably on shared environments among family members. We expect that our findings add insight to determinants of common dermatologic traits, and serve as a reference for biologic studies.

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.

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.

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.

Genetic factors have been suggested to be one of the determinants of the variation of left ventricular (LV) structure and function. However, the heritability range of LV structure varies across studies and the influence of genetics on LV function is not well established, especially in Asian populations. Study subjects were 1,642 healthy Korean adults from 426 families, consisting of 298 pairs of monozygotic twins, 62 pairs of dizygotic twins, one set of triplets, 567 siblings, and 354 parents. LV structure and function were measured by M-mode and 2D echocardiography, and conventional and tissue Doppler imaging (TDI). Pairwise intra-class correlations for various familial relationships and heritability were estimated for LV structure and function. The heritability of LV mass, LV ejection fraction (LVEF), left atrial volume index, the ratio between early and late diastolic velocity of mitral inflow (E/A ratio), and the ratio between early diastolic velocity of mitral inflow and early diastolic mitral annular velocities (E/Ea ratio) was 0.44, 0.27, 0.44, 0.25, and 0.33, respectively. Bivariate genetic analysis showed that LV structural and functional traits had significant genetic correlations with cardiovascular risk factors. Additive genetic correlation (ρG) of LV mass with body mass index, systolic blood pressure, and high density lipoprotein cholesterol were 0.49, 0.42, and -0.15 respectively. LVEF (ρG = 0.33) and left atrial volume index (ρG = 0.24) also had a significant genetic correlation with systolic blood pressure. These findings support the theory that genetic factors have significant influence on these traits and necessitate further work to identify the specific genes involved.

We aimed to assess the non-genetic contribution to the associations between the change in weight and changes in cardiovascular disease (CVD) risk factors. This analysis included 194 Korean monozygotic (MZ) twin pairs (116 men, 272 women; mean age, 38.5 ± 6.8 years) who were first examined for weight and CVD risk factors (blood pressure (BP), glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL)) between December 2005 and December 2008, and returned for a repeat examination after 2.7 ± 0.9 years. The within-pair correlations were 0.21 for the change in weight and 0.05-0.42 for the changes in CVD risk factors. Bivariate analyses showed significant environmental correlations shared between the change in weight and the changes in CVD risk factors (p < .05), except for glucose, while there were no significant genetic effects shared between the phenotypes. After adjusting for baseline values of weight, smoking, and alcohol consumption, diastolic blood pressure (DBP), TG, TC, and LDL significantly increased by 1.6 mmHg, 0.09 mmol/L, 0.10 mmol/L, and 0.09 mmol/L, respectively, per 1 kg increase in within-pair differences in weight change. In Korean MZ twins, similarity between twins for changes in weight and CVD risk factors were small to moderate, and non-genetic factors were responsible for the associations between the change in weight and changes in DBP, TG, TC, and LDL.

The International Network of Twin Registries (INTR) aims to foster scientific collaboration and promote twin research on a global scale by working to expand the resources of twin registries around the world and make them available to researchers who adhere to established guidelines for international collaboration. Our vision is to create an unprecedented scientific network of twin registries that will advance knowledge in ways that are impossible for individual registries, and includes the harmonization of data. INTR will also promote a broad range of activities, including the development of a website, formulation of data harmonization protocols, creation of a library of software tools for twin studies, design of a search engine to identify research partners, establishment of searchable inventories of data and biospecimens, development of templates for informed consent and data sharing, organization of symposia at International Society of Twin Studies conferences, support for scholar exchanges, and writing grant proposals.

We aimed to investigate the association between weight change from 20 years of age and insulin resistance (IR), and genetic and environmental relationships between these traits. In 594 Korean twins and family members (209 men, 385 women, 44.0 ± 10.8 years old), the percentage of weight change was calculated using self-reported body weight at 20 years of age and currently measured bodyweight. IR traits were assessed using fasting plasma glucose and insulin, the homeostasis model assessment of IR index (HOMA-IR), and the quantitative insulin sensitivity check index (QUICKI). Linear mixed analysis was applied after adjusting for household, body mass index (BMI) at the age of 20 years, age, sex, alcohol, smoking, physical activity, and caloric intake. Heritabilities and genetic and environmental correlations were estimated after adjusting for covariates. In 55 monozygotic twin pairs discordant for HOMA-IR level by >0.3, a conditional logistic regression analysis was conducted regarding weight change. Increases in glucose, insulin, and HOMA-IR and a decrease in QUICKI were associated with a higher percentage of weight change (p < .05). Estimated heritabilities for IR traits were 0.401–0.606 (p < .001). In cross-trait relationships, environmental correlations were -0.43–0.42 (p < .05 for all IR), while genetic correlations were -0.27–0.27 (p < .05 for QUICKI, insulin, and HOMA-IR). In 55 pairs of monozygotic twins, the odds ratio (95% confidence interval) for having a higher level of HOMA-IR was 1.10 (1.03–1.17) with 1% increase in weight change since 20 years old, after adjusting for lifestyle-related factors. In conclusion, both genetic and environmental influences played significant roles in the positive association between weight change from 20 years of age and IR.

Hallux valgus (HV) is a common foot deformity of multifactorial etiology, but knowledge about the relative importance of genetics and environments on HV has been limited. In order to estimate genetic influences on HV, 1,265 adults, including 175 monozygotic twin (MZ) pairs, 31 dizygotic twin (DZ) pairs, and 853 first-degree singleton family members of the twins were included from the Healthy Twin study, a population-based twin-family cohort in Korea. All participants underwent foot examination and weight-bearing radiographic assessment (anterior-posterior and lateral) in addition to a general health survey. Of the subjects, 208 (16.4%) were classified as HV (as HV angle >20°). The genetic influence on HV was estimated to be substantial; the heritability of HV was 0.51 (95% CI 0.42–0.59) and the heritability of HV angle was 0.47 (0.38–0.56), while contributions from shared environmental effects were negligible. These findings suggest that genetic factors play an important role in determining HV deformity.

Despite the need to provide evidence-based health policy, most developing countries suffer from a lack of resources for sound epidemiologic evidence. Most twin registers have been established in developed countries and there are relatively fewer twin registers in developing countries. Considering the immense potential of twin research, it will be worthwhile to attempt to establish a new twin register in Mongolia, where biomedical studies are still scarce. Our objectives were to initiate the process of establishing a nation-wide twin register in Mongolia, based on a nation-wide, population-based database. With the approval and support of the Ministry of Population Development and Social Welfare of Mongolia, we were able to access an initial list of 411 twin pairs who live in the district of Ulaanbaatar, the capital city of Mongolia. By developing a questionnaire to estimate zygosity, we conducted a pilot survey. Those who registered consisted of 822 individuals or 411 twin pairs (same sex: male — 178; female — 157; different sex — 76), two sets of triplets (same sex: female — 2). The age of twins ranged from 1 to 81 (mean age 7.3 ± 11.3), and 52.4% were males. The first twin survey in Mongolia not only resulted in interim data for the Mongolian Twin Register, but has the potential for establishing a larger register by using the national database. It has been proven possible to establish a twin register for research purposes in Mongolia.

The Healthy Twin Study, Korea (HT) is an ongoing multi-center cohort study that was initiated in 2005, based on a nation-wide twin and family database. Since its inception, the HT has recruited 815 pairs of adult twins and a total of 3,690 individual twins and their families as of July 2012. Here we summarize updates since the previous report in 2006. Besides the increase in size, the HT has been enriched in several aspects: a biobank was constructed for ongoing and future omics studies; and genome-wide single nucleotide polymorphism markers (Affymetrix GeneChip version 6.0, 1 M probes) have been analyzed for 2,200 individuals, which enabled gene identification studies for measured phenotypes. In addition, longitudinal study protocols were established through the HT and a second wave survey was finished in 2010 with >70% follow-up rate. The parallel genome research projects were recently launched, which would expedite multi-omics studies maximizing the twin potentials such as metagenomics and epigenetics studies, and endow us with resources for recruiting more participants. We submit this report to share updates and research opportunities from the HT.

Determining valid zygosity is a basic and important requirement in a twin study, because misdiagnosing zygosity leads to biased results. The Healthy Twin Study has collected data from adult like-sex twins and their families since 2005. In the study, a questionnaire to determine zygosity was developed comprising four questions; one concerning the degree of resemblance, and three concerning the degree of confusion by the resemblance. Among 2,761 individuals (624 twin pairs) of twin and their families, 406 pairs of twins (mean age 38.3, 63.5% women) with both questionnaire and genotype information were selected to examine the validity of the zygosity questionnaire using 16 short tandem repeat markers. We first determined individual zygosity including undetermined category, and then decided the zygosity of a twin pair using a decision tree. Sensitivity of questionnaire diagnosis was 98.8% for monozygotic (MZ) and 88.9% for dizygotic (DZ) twins, and positive predictive value was 97.2% for MZ and 95.0% for DZ. When we compared correctly and wrongly diagnosed twin pairs, misdiagnosed DZ twins (nine pairs) showed striking similarity in stature or obesity even exceeding that of true MZ twins. Our finding suggests that a parsimonious questionnaire method of diagnosing the zygosity will be useful, and adding physical or physiological measurements to a questionnaire of zygosity diagnosis will either confound the correct diagnosis or reduce the efficiency of the study compared with using questionnaire alone or with introducing genotyping.

We explored heritabilities of the State and Trait Anxiety Inventory (STAI) and the Alcohol Use Disorders Identification Test (AUDIT), and associations including genetic and environmental correlations between the phenotypes among Korean twins and their families. We analyzed the data of 1,748 participants (835 men, 913 women, 656 individuals of monozygotic twins, 173 individuals of same-sexed dizygotic twins, 919 non-twin family members, age 30–79 years) from the Healthy Twin study. Heritabilities and bivariate analyses were assessed using the SOLAR package software. In the methods of generalized estimation equations, women in the 4th quartile of state and trait scores were 17% and 15%, respectively more likely to be hazardous alcohol users compared to women in the lower three quartiles (P < .05). However, there were no significant associations between these phenotypes in men. After adjusting for age and squared age, the heritability estimates were 0.26 in men and 0.34 in women for the state score; for the trait score, 0.35 in men and 0.31 in women; for the AUDIT score, 0.32 in men and 0.37 in women (P < .001). After adjusting for age and squared age, there was a significant genetic correlation between the trait score and the AUDIT score, and a significant non-genetic correlation between the state score and the AUDIT score in women, while there were no significant genetic or non-genetic correlations between these phenotypes in men. The STAI and AUDIT scores are heritable in Koreans and the relationships between these phenotypes may be inconsistent by sex.

‘Healthy Twin’ is a twin family study extension of the existing Korean Twin-Family Register. Healthy Twin recruits adult like-sex twins over the age of 30 and their adult family members. Healthy Twin protocols are primarily tailored to the study of the quantitative trait loci of complex traits as well as to the role of environment in the etiology of complex diseases. A full-length survey is underway, including questionnaires, health examinations and the collection of biological specimens. So far, 820 individuals (169 twin pairs and their families) have participated in the survey and 1068 individual twins (608 twin pairs) have replied to the mailed zygosity questionnaire as of July 2006. The first phase (2005–2006) of Healthy Twin will recruit 1550 individuals (including about 380 twin pairs), and the second phase a proposed 1500 to 2500 additional participants. We report study protocols and zygosity and the distribution of family size of the study participants.

The Korean Twin Registry is the first nationwide twin study in Korea. We compiled 154,783 twin pairs from existing nationwide data sources, mainly from address and national health insurance data. The coverage of this registry was almost complete for the twins born since 1970, but less complete as age increased, so that there were only 990 pairs who were born before 1930. The twins' health examination (N = 54,390 persons) and questionnaire (N = 44,546 persons) results were incorporated into the registry, yielding 12,894 and 9074 concordantly informative pairs. Morbidity and mortality outcomes have been followed up since 1990, for most diseases. For preliminary analysis of complex diseases, we selected ventricular septal defects (VSD) in young twins, stomach and colorectal cancers in adult twins. We identified 353 VSDs, 284 stomach cancers, and 116 colorectal cancers among twins. The prevalence rates of cancers, but not that of VSD, were lower in twins than those in population. The difference in the cancer prevalence was marked for twins born before 1926, implying some degree of selection. Like-sex (LS) twins showed familial recurrence risks (λLS) of 41.2 for VSD and 22.4 for colorectal cancers, and 1.74 for stomach cancers. For opposite-sex (OS) twins, we could estimate λOS of 19.8 for VSD only. These results were compatible with previous studies for VSD and colorectal cancers, but not for stomach cancers. Despite the strength in size, availability of health outcomes, and some lifestyle and basic laboratory data, we need accurate zygosity information to improve the validity of the results.