The Population-Based Hungarian Twin Registry: An Update.

Between 2006 and 2021, the Hungarian Twin Registry (HTR) operated a volunteer twin registry of all age groups (50% monozygotic [MZ], 50% dizygotic [DZ], 70% female, average age 34 ± 22 years), including 1044 twin pairs, 24 triplets and one quadruplet set. In 2021, the HTR transformed from a volunteer registry into a population-based one, and it was established in the Medical Imaging Centre of Semmelweis University in Budapest. Semmelweis University's innovation fund supported the development of information technology, a phone bank and voicemail infrastructure, administrative materials, and a new website was established where twins and their relatives (parent, foster parent or caregiver) can register. The HTR's biobank was also established: 157,751 individuals with a likely twin-sibling living in Hungary (77,042 twins, 1194 triplets, 20 quadruplets, and one quintuplet) were contacted between February and March of 2021 via sealed letters. Until November 20, 2022, 12,001 twin individuals and their parents or guardians (6724 adult twins, 3009 parents/guardians and 5277 minor twins) registered, mostly online. Based on simple self-reports, 37.6% of the registered adults were MZ twins and 56.8% were DZ; 1.12% were triplets and 4.5% were unidentified. Of the registered children, 22.3% were MZ, 72.7% were DZ, 1.93% were triplets, and 3.05% were unidentified. Of the registered twins, 59.9% were female (including both the adult and minor twins). The registration questionnaire consists of eight parts, including socio-demographic and anthropometric data, smoking habits and medical questions (diseases, operations, therapies). Hungary's twin registry has become the sole and largest population-based twin registry in Central Eastern Europe. This new resource will facilitate performing world-class modern genetic research.

Which adolescent factors predict alcohol misuse in young adulthood? A co-twin comparisons study.

BACKGROUND AND AIMS: Research on adolescent predictors of later alcohol misuse is typically conducted on samples of singletons, and associations may be confounded by between-family differences. To address potential confounding, we applied a co-twin comparison design to evaluate whether differences between co-twins in a wide array of adolescent risk factors predicted differences in young adult alcohol misuse. DESIGN: Longitudinal study in which associations between characteristics of the sample as adolescents were used to predict young adult alcohol misuse in individual-level analyses and co-twin comparisons. SETTING: Finland. PARTICIPANTS: A total of 3402 individuals (1435 complete twin pairs; 36% monozygotic; 57% female) from the FinnTwin12 study. MEASUREMENTS: The young adult alcohol misuse outcome was a composite score of alcohol use and intoxication frequency. Adolescent predictors included factor scores representing academic performance, substance use, externalizing problems, internalizing problems, peer environment, physical health and relationship with parents; and single measures tapping alcohol expectancies, life events and pubertal development. FINDINGS: In individual-level analyses, individuals with higher adolescent substance use, externalizing problems, time with friends, peer deviance, sports involvement, sleeping difficulties, parental discipline, positive alcohol expectancies and difficulty of life events reported higher alcohol misuse in young adulthood (Ps < 0.019, R2  = 0.0003-0.0310%). Conversely, those with higher adolescent internalizing problems, parent-child relationship quality and time with parents reported lower alcohol misuse (Ps < 0021, R2  = 0.0018-0.0093%). The associations with adolescent substance use and alcohol expectancies remained significant in co-twin comparisons (Ps < 0.049, R2  = 0.0019-0.0314%). Further, academic performance emerged as a significant predictor, such that individuals with higher grades compared with their co-twin reported higher young adult alcohol misuse (Ps < 0.029, R2  = 0.0449-0.0533%). CONCLUSIONS: Adolescent substance use, positive alcohol expectancies and higher academic performance appear to be robust predictors of later alcohol misuse.

Twin pregnancy with two live fetuses at 11-13 weeks: effect of one fetal death on pregnancy outcome.

OBJECTIVES: First, to compare the incidence of single and double fetal death between monochorionic (MC) and dichorionic (DC) twin pregnancies with two live fetuses at 11-13 weeks' gestation and no major abnormalities. Second, to investigate the relationship between gestational age at single fetal death and interval to delivery of the cotwin. Third, to determine the rate of early preterm birth in DC and MC twin pregnancies with two live fetuses and those with single fetal death. METHODS: This was a retrospective analysis of prospectively collected data on twin pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation between 2002 and 2019. The outcome measures, which were stratified by chorionicity, were: first, death of both fetuses at presentation or death of one fetus followed by delivery of a live or dead cotwin within the subsequent 3 days at < 34 weeks' gestation; second, in pregnancies with single fetal death at < 34 weeks' gestation and a live cotwin ≥ 3 days later, the subsequent risk of fetal death and gestational-age distribution at birth of the cotwin; and, third, the gestational-age distribution at birth in pregnancies with two live fetuses. RESULTS: The main findings of this study of 4896 DC and 1329 MC twin pregnancies with two live fetuses at 11-13 weeks' gestation were: first, the rate of death of both twins or death of one fetus and delivery of the live or dead cotwin within 3 days was higher in MC than in DC twin pregnancies; second, the rate of single fetal death with a live cotwin ≥ 3 days later was higher in MC than in DC twin pregnancies, but the rate of subsequent cotwin death in MC twin pregnancies was not significantly different from that in DC twin pregnancies; third, in pregnancies with two live fetuses, the rate of early preterm birth was significantly higher in MC than in DC twin pregnancies; fourth, the rate of early preterm birth in pregnancies with single fetal death and a live cotwin ≥ 3 days later was not significantly different between MC and DC twin pregnancies but the rates were substantially higher than in those with two live fetuses; and, fifth, in both MC and DC pregnancies with single fetal death and a live cotwin ≥ 3 days later, there was a significant inverse association between gestational age at death and interval to delivery (mean interval of 19 weeks for death at 15 weeks and mean interval of 2.5 weeks for death at 30 weeks). CONCLUSIONS: First, in MC twin pregnancies, the risk of single or double fetal death is higher than in DC twins. Second, in both MC and DC twin pregnancies, the rate of early preterm birth is higher in those with one fetal death than in those with two live fetuses. Third, in both MC and DC twins with one fetal death, the interval to delivery is related inversely to gestational age at fetal death. These data should be useful in counseling parents as to the likely outcome of their pregnancy after single fetal death and in defining strategies for surveillance in the management of these types of twin pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Intertwin discordance in fetal size at 11-13 weeks' gestation and pregnancy outcome.

OBJECTIVE: To investigate the value of intertwin discordance in fetal crown-rump length (CRL) at the 11-13-week scan in the prediction of adverse outcome in dichorionic (DC), monochorionic diamniotic (MCDA) and monochorionic monoamniotic (MCMA) twin pregnancies. METHODS: This was a retrospective analysis of prospectively collected data on twin pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation between 2002 and 2019. In pregnancies with no major abnormalities, we examined the value of intertwin discordance in fetal CRL in DC, MCDA and MCMA twins in the prediction of fetal loss at < 20 and < 24 weeks' gestation, perinatal death at ≥ 24 weeks, preterm delivery at < 32 and < 37 weeks, birth of at least one small-for-gestational-age (SGA) neonate with birth weight < 5th percentile and intertwin birth-weight discordance of ≥ 20% and ≥ 25%. RESULTS: First, the study population of 6225 twin pregnancies included 4896 (78.7%) DC, 1274 (20.4%) MCDA and 55 (0.9%) MCMA twin pregnancies. Second, median CRL discordance in DC twin pregnancies (3.2%; interquartile range (IQR), 1.4-5.8%) was lower than in MCDA twins (3.6%; IQR, 1.6-6.2%; P = 0.0008), but was not significantly different from that in MCMA twins (2.9%; IQR, 1.2-5.1%; P = 0.269). Third, compared to CRL discordance in DC twin pregnancies with two non-SGA live births at ≥ 37 weeks' gestation, there was significantly larger CRL discordance in both DC and MCDA twin pregnancies complicated by fetal death at < 20 and < 24 weeks' gestation, perinatal death at ≥ 24 weeks, preterm birth at < 32 and < 37 weeks, birth of at least one SGA neonate and birth-weight discordance ≥ 20% and ≥ 25%, and in MCDA twin pregnancies undergoing endoscopic laser surgery. Fourth, the predictive performance of CRL discordance for each adverse pregnancy outcome was poor, with areas under the receiver-operating-characteristics curves ranging from 0.533 to 0.624. However, in both DC and MCDA twin pregnancies with large CRL discordance, there was a high risk of fetal loss. Fifth, in DC twin pregnancies, the overall rate of fetal loss at < 20 weeks' gestation was 1.3% but, in the small subgroup with CRL discordance of ≥ 15%, which constituted 1.9% of the total, the rate increased to 5.3%. Sixth, in MCDA twin pregnancies, the rate of fetal loss or endoscopic laser surgery at < 20 weeks was about 11%, but, in the small subgroups with CRL discordance of ≥ 10%, ≥ 15% and ≥ 20%, which constituted 9%, < 3% and < 1% of the total, the risk was increased to about 32%, 49% and 70%, respectively. Seventh, in MCMA twin pregnancies, there were no significant differences in CRL discordance for any of the adverse outcome measures, but this may be the consequence of the small number of cases in the study population. CONCLUSIONS: In both DC and MCDA twin pregnancies, increased CRL discordance is associated with an increased risk of fetal death at < 20 and < 24 weeks' gestation, perinatal death at ≥ 24 weeks, preterm birth at < 37 and < 32 weeks, birth of at least one SGA neonate and birth-weight discordance ≥ 20% and ≥ 25%, but CRL discordance is a poor screening test for adverse pregnancy outcome. However, in DC twins, CRL discordance of ≥ 15% is associated with an increased risk of fetal loss at < 20 and < 24 weeks' gestation and, in MCDA twins, CRL discordance of ≥ 10%, and more so discordance of ≥ 15% and ≥ 20%, is associated with a very high risk of fetal loss or endoscopic laser surgery at < 20 and < 24 weeks and this information is useful in counseling women and defining the timing for subsequent assessment and possible intervention. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Rotator Cuff Degeneration: The Role of Genetics.

BACKGROUND: The literature is certain regarding the multifactorial etiology of rotator cuff degeneration. However, it remains unclear if rotator cuff degeneration exclusively depends on intrinsic and extrinsic factors or if it is also genetically determined. We compared the health status of cuff tendons, evaluated with a magnetic resonance imaging (MRI) study, between elderly monozygotic and dizygotic twins with the aim of separating the contributions of genetics from shared and unique environments. METHODS: The rotator cuff tendon status was assessed using the Sugaya classification by MRI. Heritability, defined as the proportion of total variance of a specific characteristic in a particular population due to a genetic cause, was calculated as twice the difference between the intraclass correlation coefficients for monozygotic and dizygotic pairs. The influence of shared environment, which contributes to twin and sibling similarity, was calculated as the difference between the monozygotic correlation coefficient and the heritability index. RESULTS: We identified 33 pairs of elderly twins: 17 monozygotic pairs and 16 dizygotic pairs, with a mean age (and standard deviation) of 64.62 ± 3.32 years. The polychoric correlation was 0.62 in monozygotic twins and 0.53 in dizygotic twins. The calculated heritability index was 0.18 (18%), and the contribution was 0.44 (44%) for the shared environment and 0.38 (38%) for the unique environment. CONCLUSIONS: The role of genetics in rotator cuff degeneration is quantified by our study on elderly monozygotic and dizygotic twins; however, it is only partial with respect to the contribution of shared and unique environments.

Birth Anomalies in Monozygotic and Dizygotic Twins: Results From the California Twin Registry.

BACKGROUND: Inherited factors and maternal behaviors are thought to play an important role in the etiology of several congenital malformations. Twin studies can offer additional evidence regarding the contribution of genetic and lifestyle factors to common birth anomalies, but few large-scale studies have been reported. METHODS: We included data from twins (20,803 pairs) from the population-based California Twin Program. We compared concordance in monozygotic (MZ) to dizygotic (DZ) twins for the following birth anomalies: clubfoot, oral cleft, spina bifida, muscular dystrophy, deafness, cerebral palsy, strabismus, and congenital heart defects. Each birth anomaly was also examined for the associations with birth characteristics (birthweight and birth order) and parental exposures (age, smoking, and parental education). RESULTS: The overall prevalence of any selected birth anomaly in California twins was 38 per 1,000 persons, with a slightly decreasing trend from 1957-1982. For pairwise concordance in 6,752 MZ and 7,326 like-sex DZ twin pairs, high MZ:DZ concordance ratios were observed for clubfoot (CR 5.91; P = 0.043) and strabismus (CR 2.52; P = 0.001). Among the total 20,803 pairs, parental smoking was significantly associated with risk of spina bifida (OR 3.48; 95% CI, 1.48-8.18) and strabismus (OR 1.61; 95% CI, 1.28-2.03). A significant quadratic trend of increasing risk for clubfoot, spina bifida, and strabismus was found when examining whether father smoked, mother smoked, or both parents smoked relative to non-smoking parents (P = 0.029, 0.026, and 0.0005, respectively). CONCLUSIONS: Our results provide evidence for a multifactorial etiology underlying selected birth anomalies. Further research is needed to understand the biological mechanisms.

Etiology of Hypomineralized Second Primary Molars: A Prospective Twin Study.

The etiology of hypomineralized second primary molars (HSPM) is unclear, but genetic and environmental factors have been proposed. The aim of this study was to investigate the relative contribution of genes and environment to the etiology of HSPM and to identify potential environmental risk factors in a longitudinal twin cohort. Children from twin pregnancies ( N = 250) were recruited antenatally, and detailed demographic, health, and phenotypic data were collected at recruitment, 24- and 36-wk gestation, birth, and 18 mo of age. 25-Hydroxyvitamin D was quantified for mothers at 28-wk gestation and infants at birth. Dental examinations were conducted on the twins at 6 y of age to determine the presence, severity, and extent of HSPM per standardized criteria. To investigate associations of environmental risk factors with HSPM, multiple logistic regression models were fitted with generalized estimating equations to adjust for twin correlation. Within- and between-pair analyses were performed for unshared continuous variables: birthweight and birth 25-hydroxyvitamin D. Twin-twin concordance for monozygotic (MZ) and dizygotic (DZ) pairs was calculated and compared after adjusting for identified risk factors. A total of 344 twins underwent the 6-y-old dental assessment; HSPM occurred in 68 (19.8%). After adjusting for potential confounders, vitamin D levels at birth, infantile eczema, dizygosity, in vitro fertilization, socioeconomic position, and maternal smoking beyond the first trimester of pregnancy demonstrated the strongest associations with HSPM. Overall concordance for HSPM was 0.47 (95% CI, 0.32 to 0.62) with weak evidence ( P = 0.078) of higher concordance in MZ twins (0.63; 95% CI, 0.38 to 0.89) as compared with DZ twins (0.41; 95% CI, 0.24 to 0.58). After adjusting for known risk factors, there was no evidence ( P = 0.172) for an additive genetic influence. These findings suggest that shared and unshared environmental factors, such as maternal smoking later in pregnancy and infantile eczema, are important in the etiology of HSPM.

Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes.

OBJECTIVE: There are variable reports of risk of concordance for progression to islet autoantibodies and type 1 diabetes in identical twins after one twin is diagnosed. We examined development of positive autoantibodies and type 1 diabetes and the effects of genetic factors and common environment on autoantibody positivity in identical twins, nonidentical twins, and full siblings. RESEARCH DESIGN AND METHODS: Subjects from the TrialNet Pathway to Prevention Study (N = 48,026) were screened from 2004 to 2015 for islet autoantibodies (GAD antibody [GADA], insulinoma-associated antigen 2 [IA-2A], and autoantibodies against insulin [IAA]). Of these subjects, 17,226 (157 identical twins, 283 nonidentical twins, and 16,786 full siblings) were followed for autoantibody positivity or type 1 diabetes for a median of 2.1 years. RESULTS: At screening, identical twins were more likely to have positive GADA, IA-2A, and IAA than nonidentical twins or full siblings (all P < 0.0001). Younger age, male sex, and genetic factors were significant factors for expression of IA-2A, IAA, one or more positive autoantibodies, and two or more positive autoantibodies (all P ≤ 0.03). Initially autoantibody-positive identical twins had a 69% risk of diabetes by 3 years compared with 1.5% for initially autoantibody-negative identical twins. In nonidentical twins, type 1 diabetes risk by 3 years was 72% for initially multiple autoantibody-positive, 13% for single autoantibody-positive, and 0% for initially autoantibody-negative nonidentical twins. Full siblings had a 3-year type 1 diabetes risk of 47% for multiple autoantibody-positive, 12% for single autoantibody-positive, and 0.5% for initially autoantibody-negative subjects. CONCLUSIONS: Risk of type 1 diabetes at 3 years is high for initially multiple and single autoantibody-positive identical twins and multiple autoantibody-positive nonidentical twins. Genetic predisposition, age, and male sex are significant risk factors for development of positive autoantibodies in twins.

Heritability of Facial Skeletal and Dental Characteristics of Monozygotic and Dizygotic Twins Using Cephalometric Analysis and Falconer's Method.

The purpose of this study was to investigate the heritability of facial skeletal and dental characteristics of the monozygotic (MZ) and dizygotic (DZ) twins. The samples consisted of Korean MZ and DZ twins (n = 13 pairs/each twin; 7 pairs of males and 6 pairs of females; mean age, 39 years, respectively). The linear, angular, and ratio variables, which could describe the size and shape of the facial horizontal and vertical, dental, mandible and cranial base structure, were measured. The Falconer's method was used to calculate the heritability (h; close to or below 0, low heritability; close to or above 1, high heritability). In the facial horizontal and vertical aspects, the highest h values were shown at SNA (degree, 1.53), SNB (degree, 2.12), SN-Pog (degree, 2.19), SN-palatal plane angle (degree, 1.29), SN-mandibular plane angle (degree, 1.59), N-ANS/ANS-Me (1.66), and ANS-Me/N-Me (1.62). In the dental aspects, although L1-occlusal plane angle (degree, 1.38) and SN-occlusal plane angle (degree, 2.09) showed high h values, most of the dental variables showed low h values. In the mandible and cranial base, lower gonial angle, mandibular body length, and cranial base angle showed high h values (N-Go-Gn [degree], 1.07; Go-Pog [mm], 0.92; N-S-Ba [degree], 1.51). The descending order of the overall mean h values was the facial horizontal (1.10), facial vertical (0.71), mandible (0.59), cranial base (0.37), and dental characteristics (-0.11). The shape of facial skeletal structure and location of the occlusal plane within skeletal framework was more influenced by genetic factors than environmental factors.

Exploring the association between genetic and environmental factors and molar incisor hypomineralization: evidence from a twin study.

BACKGROUND: The etiology of molar-incisor hypomineralization (MIH) remains unknown. Studies indicate that it is multifactorial, and that genetic and environmental factors are involved. Research with twins provides important subsidy to investigate the Influence of genetics and environmental factors that act during pregnancy on the etiology of alterations. AIM: This cross-sectional study evaluated the agreement of molar incisor hypomineralization (MIH) between monozygotic and dizygotic twin pairs and the association with environmental factors. DESIGN: The sample consisted of 167 pairs of twins (8-15 years old), 94 monozygotic and 73 dizygotic. The parents answered a questionnaire on sociodemographic data and pre-, peri-, and postnatal health. A dental examination was performed by two calibrated examiners (Kappa ≥0.88) for MIH diagnosis, following the criteria proposed by the European Academy of Pediatric Dentistry in 2003. RESULTS: The prevalence of MIH was 29.3%. There was greater concordance of MIH between monozygotic twins for affected first molars and permanent incisors (P = 0.0012) and pairs of twins assessed (P = 0.0211). The presence of MIH was associated with family income between one and two wages (P = 0.009, prevalence ratio [PR] = 3.82, confidence interval [CI 95%] 1.40-10.44), above two wages (P = 0.007, PR = 4.60, 95% CI: 1.51-14.05), and gestational hemorrhage (P = 0.032, PR = 5.70, 95% CI: 1.16-28.14). CONCLUSIONS: The greater concordance in the diagnosis of MIH among monozygotic twins indicates a genetic influence, although environmental factors, such as family income and hemorrhage during pregnancy, are also associated with the occurrence of MIH.

Sleep Duration, Mortality, and Heredity-A Prospective Twin Study.

Introduction: A number of studies have shown a U-shaped association between sleep duration and mortality. Since sleep duration is partly genetically determined, it seems likely that its association with mortality is also genetically influenced. The purpose of the present study was to investigate the influence on heredity on the association between sleep duration and mortality. Methods: We used a cohort of 14267 twins from the Swedish Twin Registry. Results: A Cox proportional hazards regression analysis, adjusted for a number of covariates, confirmed a clear U shape with a hazard ratio (HR) = 1.34 and 95% confidence interval (CI) = 1.15-1.57 for a sleep duration of ≤6.5 hours and HR = 1.18 (CI = 1.07-1.30) for sleep of ≥9.5 hours. Reference value was 7.0 hours. A co-twin analysis of 1942 twins discordant on mortality showed a HR = 2.66 (CI = 1.17-6.04) for long (≥9.5 hours) sleep in monzygotic twins and an HR = 0.66 (CI = 0.20-2.14) for short (<6.5 hours) sleep. In dizygotic twins, no association was significant. The heritability for mortality was 28% for the whole group, while it was 86% for short sleepers and 42% for long sleepers. Thus, the link with mortality for long sleep appears to be more due to environmental factors than to heredity, while heritability dominates among short sleepers. Conclusions: We found that both long and short sleep were associated with higher total mortality, that the difference in mortality within twin pairs is associated with long sleep, and that short sleep has a higher heritability for mortality, while long sleep is associated with more environmental influences on mortality.

Risk Factors and Relationship of Cutaneous and Uveal Melanocytic Lesions in Monozygotic and Dizygotic Twin Pairs.

BACKGROUND: The similar genetic background of a pair of twins, and the similar environmental impacts to which they are exposed allow an exact and objective investigation of various constitutional and environmental factors in naevus development. As far as we are aware, this is the first published survey that simultaneously examines cutaneous and ocular pigmented lesions in an appreciable sample of identical and non-identical twins. METHODS: 172 pairs of twins of Caucasian origin were included in this study. A whole-body skin examination and a detailed ophthalmological examination were performed to determine the density of melanocytic lesions. A standardized questionnaire was used to assess the data relating to constitutional, sun exposure and other variables. RESULTS: A notably high proportion of the subjects (36.78%) manifested one or more clinically atypical melanocytic naevi (CAMNs), and approximately one-third (31.4%) of them at least one benign uveal pigmented lesion (BUPL). The incidence of iris freckles (IFs), iris naevi (INs) and choroidal naevi (CHNs) proved to be 25.35%, 5.98% and 3.52%, respectively. The interclass correlation coefficients for common melanocytic naevi (CMNs), CAMNs, and INs were 0.77, 0.76 and 0.86 in monozygotic twins, as compared with 0.5, 0.27 and 0.25 in dizygotic twin pairs, respectively. A statistically significant correlation was found between the prevalence of CAMNs and that of INs. CONCLUSIONS: This significant correlation suggests the existence of a subgroup of Caucasian people with an increased susceptibility to both cutaneous and ocular naevus formation. There is accumulating evidence that, besides the presence of cutaneous atypical naevi, INs can serve as a marker of a predisposed phenotype at risk of uveal melanoma. The correlation between cutaneous and ocular pigmented lesions underlines the need for the adequate ophthalmological screening of subjects with CAMNs and INs.

Adolescent cannabis use and repeated voluntary unprotected sex in women.

BACKGROUND AND AIMS: Substance use has been implicated in the onset and maintenance of risky sexual behaviors, which have particularly devastating consequences in young women. This study examined whether (i) adolescent onset of cannabis use is associated with repeated voluntary unprotected sex in women and (ii) whether this association persists after accounting for correlated familial influences. DESIGN: General population sample of female twins. SETTING: Midwestern United States. PARTICIPANTS: A total of 2784 sexually active twin women (15.5% African American) aged 18-27 years (assessed 2002-05), including 119 dizygotic (DZ) and 115 monozygotic (MZ) discordant pairs. MEASUREMENTS: Self-report interview data on cannabis use that first occurred prior to age 17 (27.1%) and repeated voluntary unprotected sex (27.2%). Key covariates included early onset of regular drinking, regular smoking, sexual debut and menstruation as well as conduct disorder symptoms and childhood sexual abuse. FINDINGS: Compared with never users and those who started using cannabis at a later age, adolescent cannabis users were more likely to report repeated voluntary unprotected sex [odds ratio (OR) = 2.69; 95% confidence interval (CI) = 2.24-3.22]. Genetic (rg  = 0.57, 95% CI = 0.38-0.87) and non-shared environmental (re  = 0.21, 95% CI = 0.02-0.38) factors contributed to the association. After accounting for correlated familial factors, there was a consistent elevation in the likelihood of repeated voluntary unprotected sex in the exposed twin relative to her genetically identical never/late-onset user co-twin (unadjusted OR = 2.25, 95% CI = 1.14-4.44), even after adjustment for covariates (adjusted OR = 2.27, 95% CI = 1.08-4.80). CONCLUSIONS: Women who start using cannabis during adolescence appear to be more likely to report voluntary engagement in repeated unprotected sex than women who never use cannabis or who initiate cannabis use after adolescence. The results appear to be independent of shared genetic influences.

The effects of social anxiety on alcohol and cigarette use across adolescence: Results from a longitudinal twin study in Finland.

Conflicting reports exist on the direction of the relationship between social anxiety (SA) and alcohol/cigarette use (AU/CU) and alcohol/nicotine dependence (AD/ND), with both positive and negative associations reported. A prospective, longitudinal sample of Finnish twins (n = 1,906) was used to test potential explanations for these discrepancies. Specifically, this study used peer, parent, and teacher ratings of SA, and a clinical interview screening item for social anxiety disorder (SAD-Sc) to examine associations between SA and AU/CU and AD/ND from early adolescence into young adulthood. Peer-rated SA was negatively associated with AU, CU, and AD from age 14 through age 22, implying a protective effect (ß = -0.01 to -.03). Teacher- and parent-rated SA associations were in the same directions but weaker or nonsignificant, indicating that aspects of SA that are recognizable by peers may be most relevant to AU/CU. Self-reported SAD-Sc was also negatively associated with AU, but positively associated with AD symptoms in young adulthood (ß = 0.38). Our findings partially support the existence of different associations between SA and AU versus AD, but only in the context of SAD-Sc rather than trait SA. Neither trait SA nor SAD-Sc significantly predicted ND symptoms, although SAD-Sc was associated with both cigarette abstinence and daily smoking. These findings suggest that adolescent SA is modestly associated with lower AU/CU, although there may be some individuals with more severe SA who develop alcohol problems later in life. There was little evidence of a common underlying liability contributing to both SA and alcohol/cigarette use. (PsycINFO Database Record

Heritability of non-HLA genetics in coeliac disease: a population-based study in 107†000 twins.

BACKGROUND AND OBJECTIVE: Almost 100% individuals with coeliac disease (CD) are carriers of the human leucocyte antigen (HLA) DQ2/DQ8 alleles. Earlier studies have, however, failed to consider the HLA system when estimating heritability in CD, thus violating an underlying assumption of heritability analysis. We examined the heritability of CD in a large population-based sample of twins, considering HLA. DESIGN: In a population-representative sample of 107 912 twins, we identified individuals with CD (equal to villous atrophy) through biopsy reports from all Swedish pathology departments. We calculated concordance rates and tetrachoric correlations for monozygotic (MZ) and dizygotic (DZ) twin pairs. Further, we estimated heritability of CD, first strictly from observed data, and then the non-HLA heritability, representing the heritability of all genetic factors except the HLA locus, using an approach that circumvent the violation of underlying assumptions. RESULTS: We identified 513 twins with a diagnosis of CD (prevalence 0.48%). Concordance rates were higher in MZ pairs (0.49) than in DZ pairs (0.10), as were tetrachoric correlations (0.89 in MZ vs 0.51 in DZ pairs). The heritability of CD was 75% (95% CI 55% to 96%). The non-HLA heritability was slightly attenuated, 68% (95% CI 40% to 96%), with shared (17%) and non-shared (15%) environmental factors explaining the remaining variability of CD. CONCLUSIONS: CD is characterised by a high heritability, but our study also suggests that non-shared environmental factors may be of importance to CD development. HLA seems to have only moderate impact on heritability estimates.

Twin Chorionicity and the Risk of Hypertensive Disorders: Gestational Hypertension and Pre-eclampsia.

Twin gestation is known to be a risk factor for hypertensive disorders of pregnancy. However, the relationship between hypertensive disorders (pre-eclampsia (PE) and gestational hypertension (GH)) and chorionicity of twin pregnancy is unclear, and published data is conflicting. We decided to analyze the relationship between placentation and prevalence of hypertensive disorders. It was a retrospective cohort study. 312 twin pregnancies delivered between 2009 and 2014 were analyzed, 79 of which were monochorionic and 233 dichorionic. The occurrence of PE and GH was established according to American College of Obstetricians and Gynecologists' (ACOG) guidelines. Hypertensive disorders were diagnosed significantly more often in dichorionic than in monochorionic twin pregnancies (19.7% vs. 8.9%; OR = 2.53 95% CI 1.04-6.45; p = .03). PE occurred more frequently in DCP (13.3% vs. 3.8%; OR = 3.88 95% CI 1.09-16.46; p = .02). There were no differences between those two groups in the prevalence of GH (6.4% vs. 5.1%; p = .79). The logistic regression model for the occurrence of PE included chorionicity, mother's age lower than 18 or higher than 40, pre-gestational obesity, in vitro fertilization, primiparity, gestational age at delivery, gestational diabetes, and active smoking. It showed that dichorionicity remained an independent risk factor for PE (adjusted OR = 4.97.0 95% CI 1.06-23.38; p = .04). Dichorionicity seems to be a risk factor for PE but not for GH development.

Familial Risk and Heritability of Cancer Among Twins in Nordic Countries.

IMPORTANCE: Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction. OBJECTIVE: To estimate familial risk and heritability of cancer types in a large twin cohort. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 80,309 monozygotic and 123,382 same-sex dizygotic twin individuals (N = 203,691) within the population-based registers of Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50,990 individuals who died of any cause, and 3804 who emigrated and were lost to follow-up. EXPOSURES: Shared environmental and heritable risk factors among pairs of twins. MAIN OUTCOMES AND MEASURES: The main outcome was incident cancer. Time-to-event analyses were used to estimate familial risk (risk of cancer in an individual given a twin's development of cancer) and heritability (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death. RESULTS: A total of 27,156 incident cancers were diagnosed in 23,980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5% (95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%). CONCLUSIONS AND RELEVANCE: In this long-term follow-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling.

Drinking and mortality: long-term follow-up of drinking-discordant twin pairs.

AIMS: To determine if associations of alcohol consumption with all-cause mortality replicate in discordant monozygotic twin comparisons that control for familial and genetic confounds. DESIGN: A 30-year prospective follow-up. SETTING: Population-based older Finnish twin cohort. PARTICIPANTS: Same-sex twins, aged 24-60 years at the end of 1981, without overt comorbidities, completed questionnaires in 1975 and 1981 with response rates of 89 and 84%. A total of 15,607 twins were available for mortality follow-up from the date of returned 1981 questionnaires to 31 December 2011; 14,787 twins with complete information were analysed. MEASUREMENTS: Self-reported monthly alcohol consumption, heavy drinking occasions (HDO) and alcohol-induced blackouts. Adjustments for age, gender, marital and smoking status, physical activity, obesity, education and social class. FINDINGS: Among twins as individuals, high levels of monthly alcohol consumption (≥ 259 g/month) associated with earlier mortality [hazard ratio (HR) = 1.63, 95% confidence interval (CI) = 1.47-1.81]. That association was replicated in comparisons of all informatively drinking-discordant twin pairs (HR = 1.91, 95% CI = 1.49-2.45) and within discordant monozygotic (MZ) twin pairs (HR = 2.24, 95% CI = 1.31-3.85), with comparable effect size. Smaller samples of MZ twins discordant for HDO and blackouts limited power; a significant association with mortality was found for multiple blackouts (HR = 2.82, 95% CI = 1.30-6.08), but not for HDO. CONCLUSIONS: The associations of high levels of monthly alcohol consumption and alcohol-induced blackouts with increased all-cause mortality among Finnish twins cannot be explained by familial or genetic confounds; the explanation appears to be causal.

Smoking and risk for psoriasis: a population-based twin study.

BACKGROUND: Smoking is a potential risk factor for psoriasis. Both psoriasis and smoking habits are partly explained by genetic factors. However, twin studies investigating the association between these traits are limited. METHODS: Questionnaire-based data on smoking habits and psoriasis were collected for 34,781 twins, aged 20-71 years, from the Danish Twin Registry. A co-twin control analysis was performed on 1700 twin pairs discordant for lifetime history of smoking. Genetic and environmental correlations between smoking and psoriasis were estimated using classical twin modeling. RESULTS: After multivariable adjustment, age group (50-71 vs. 20-49 years) and childhood exposure to environmental tobacco smoke (ETS) were significantly associated with psoriasis in the whole population (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.02-1.29 [P = 0.021] and OR 1.28, 95% CI 1.10-1.49 [P = 0.002], respectively). Risk for psoriasis increased substantially (OR 2.18, 95% CI 1.82-2.61; P < 0.001) for smokers with a history of >5 pack-years, even after adjusting for age, sex, and childhood ETS. Among twin pairs discordant for smoking, risk for psoriasis in the ever-smoking twin was lower among monozygotic twins (OR 1.23, 95% CI 0.59-2.56; P = 0.578) than among same-sex dizygotic twins (OR 2.21, 95% CI 1.36-3.58; P = 0.001). Genetic factors explained 20% (14-25%; P < 0.001) of the correlation between psoriasis and smoking, whereas non-shared environmental factors explained 8% (0-22%; P = 0.504). CONCLUSIONS: Tobacco consumption and childhood ETS are significantly associated with psoriasis. Results indicate shared genetic factors for smoking and psoriasis.