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Virgilia Toccaceli,1 Michael Tenti,2 Maria Antonietta Stazi,1 Corrado Fagnani,1 Emanuela Medda,1 Lidia Gargiulo,3 Alessandra Burgio,3 Letizia Sampaolo,4 Maurizio Ferri,1 William Raffaeli2 1Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità (Italian National Institute of Health), Rome, Italy; 2Fondazione ISAL, Institute for Research on Pain, Torre Pedrera, Italy; 3ISTAT, National Institute of Statistics, Rome, Italy; 4Centre for Disease Prevention and Health Promotion, Istituto Superiore di Sanità (Italian National Institute of Health), Rome, ItalyCorrespondence: Michael Tenti, Fondazione ISAL, Via San Salvador, 204, Rimini, 47922, Italy, Tel +390541725166, Fax +390541725164, Email michael.tenti@fondazioneisal.itBackground: Chronic pain (CP) prevalence estimates addressing a wide phenotype are still quite fragmented and may vary widely due to the lack of standardized tools of investigation. There is an urgent need to update general population CP estimates.Methods: For this purpose, the Brief Five-item Chronic Pain Questionnaire was developed through experts’ consultations for design and content validity assessment; literature analysis of measures used to investigate CP for general population surveys; understandability evaluation through a survey on a convenience sample of affected and non-affected individuals; reliability assessment by means of two double-wave online surveys carried out by the Italian Twin Registry; criterion and construct validity assessment through the third wave of the 2019 European Health Interview Survey (Ehis).Results: Key dimensions were defined to describe CP main aspects from a public health perspective. Literature analysis showed that validated questionnaires were rarely used to address important public health CP aspects. Understandability of the measure was good. Test-retest analyses showed adequate reliability of the measure: k values were at least “moderate” with highest values regarding CP “occurrence” and “intensity”. Correlations of CP with well-known comorbidities (cancer, depression), and specific traits (age, education) as well as of CP and its intensity with “physical pain occurrence and intensity” detected in the Ehis 2019, confirmed, respectively, a good construct and criterion validity. Construct validity was also evaluated through the correlation between “perceived treatment effectiveness” and “interference of pain in daily life activities” as recorded in the Ehis 2019.Conclusion: The designed questionnaire is a brief self-administered measure, particularly suitable to detect persistent states of pain and related intensity in large-scale general population surveys by means of a first filtering item followed by four further items. It is, in fact, designed to detect CP possible underlying causes/triggers, drugs/treatments taking and frequency, and self-perceived effectiveness among CP sufferers. Further validation of the measure in different social and cultural contexts is desirable.Keywords: chronic pain, epidemiology, methodology, questionnaire, survey, European Health Interview Survey

The frequency with which Internalizing and Externalizing symptoms co-occur suggests that, behind both domains, there may be a common susceptibility represented by a general psychopathology factor. However, it’s still unclear whether this common susceptibility is affected by age-related variations. Internalizing (i.e., Fear and Distress) and Externalizing symptoms were evaluated in 803 twin pairs from the population-based Italian Twin Registry. Model-fitting analysis was performed separately in the 6–14 and 15–18 age groups to estimate genetic and environmental contributions to the covariance among symptoms. For the 6–14 group, a multivariate Cholesky model best fitted the data, while, for the 15–18 group, the best fit was provided by a Common Pathway model in which nearly 50% of total variance of each trait was mediated by common genetic factors. Our findings support a common susceptibility behind Internalizing and Externalizing symptoms, mainly genetic in origin, that becomes more evident at the beginning of puberty.

Background Italy was one of the first countries to be heavily hit by the spread of the new Coronavirus. Longitudinal studies are needed to investigate the real effect of COVID-19 on adult mental health. The Italian Twin Registry carried out a study to investigate, over time, the course of depressive symptoms in the general population. Methods The study relies on data collected just before the beginning (February 2020) and the end (June 2020) of the first lockdown. Symptoms of depression were assessed using the Patient Health Questionnaire, and total scores or categorized depression scores were considered in the analyzes. Results A total of 1690 adult twins were recruited. The study showed a mean depression score of 1.11 immediately before lockdown and 1.20 immediately after, with an overall prevalence of depressive symptoms increasing from 33.6 to 38.9%. Depressive symptoms immediately after the restriction period were associated with Covid-19 symptoms affecting households, financial problems due to the pandemic and poor social support. Independently of the baseline risk of depressive symptoms, we observed an increased risk among younger and less educated people. Compared to the pre-lockdown period, women and middle-aged people also were found to be at greater risk of developing depressive symptoms. Limitations Possible participation bias and residual selection bias. Conclusions The study shows that the COVID-19 pandemic was associated with an increased depressive symptomatology and that, in such health emergency times, the most vulnerable persons are young adults, women, and those living in a socially, culturally, or economically disadvantaged environment.

Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (β = −0.05 educational years, 95% CI −0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (β = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers. CC BY 4.0Correspondence Address: Silventoinen, K.; University of Helsinki, P.O. Box 18, Finland; email: karri.silventoinen@helsinki.fi© 2021 The Authors

Data on the etiological factors underlying the co-occurrence of common adolescent pain with anxiety and depression symptoms are very limited. Opioid prescriptions for adolescent pain problems are on the rise in North America and constitute a risk factor for diversion, misuse, and substance use. In this study, we aimed to investigate the phenotypic and etiological association among pain, depression, and anxiety and to test their link to substance use in adolescents. By taking advantage of the Italian National Twin Registry and of the relatively low incidence of opioid prescriptions in Italy, we applied multivariate modelling analyses to 748 Italian adolescent twins (374 pairs, mean age 16 ± 1.24 years). Twins' responses to the Achenbach Youth Self-Report questionnaire were used to build a composite adolescent pain index and to measure anxiety, depression, and substance use. All monozygotic within-pair correlations were higher than the dizygotic correlations, indicating genetic influences for adolescent pain, anxiety, and depressive problems. A common latent liability factor influenced by genetic and environmental elements shared among pain, depression, and anxiety provided the best fit to explain the co-occurrence of adolescent pain, anxiety, and depression problems. A common phenotypic factor capturing all 3 phenotypes was positively associated (β = 0.19, P < 0.001, confidence interval: 0.10-0.27) with substance use. These findings indicate that several intertwined mechanisms, including genetic factors, can explain a shared liability to common adolescent pain, anxiety, and depression problems. Their association with substance use remains traceable even in societies with relatively low prevalence of opioid prescriptions.

Background: Heart rate (HR), mean arterial pressure (MAP) and carotid intima–media thickness (cIMT) are moderately heritable cardiovascular traits, but the environmental effects on the longitudinal change of their heritability have never been investigated. Methods: 368 Italian and Hungarian twins (107 monozygotic, 77 dizygotic) underwent oscillometric measurement and B-mode sonography of bilateral carotid arteries in 2009/2010 and 2014. Within- -individual/cross-study wave, cross-twin/within-study wave and cross-twin/cross-study wave correlations were estimated, and bivariate Cholesky models were fitted to decompose the total variance at each wave and covariance between study waves into additive genetic, shared and unique environmental components. Results: For each trait, a moderate longitudinal stability was observed, with within-individual/crosswave correlations of 0.42 (95% CI: 0.33–0.51) for HR, 0.34 (95% CI: 0.24–0.43) for MAP, and 0.23 (95% CI: 0.12–0.33) for cIMT. Cross-twin/cross-wave correlations in monozygotic pairs were all significant and substantially higher than the corresponding dizygotic correlations. Genetic continuity was the main source of longitudinal stability, with across-time genetic correlations of 0.52 (95% CI: 0.29–0.71) for HR, 0.56 (95% CI: 0.31–0.81) for MAP, and 0.36 (95% CI: 0.07–0.64) for cIMT. Overlapping genetic factors explained respectively 57%, 77%, and 68% of the longitudinal covariance of the HR, MAP and cIMT traits. Conclusions: Genetic factors have a substantial role in the longitudinal change of HR, MAP and cIMT; however, the influence of unique environmental factors remains relevant. Further studies should better elucidate whether epigenetic mechanisms have a role in influencing the stability of the investigated traits over time.

ImportancePeople conceived using assisted reproductive technology (ART) make up an increasing proportion of the world’s population, and their numbers are expected to continue rising.ObjectiveInvestigate association of ART conception with growth and adiposity outcomes from infancy to early adulthood in offspring from a large multinational multi-cohort study.Design26 population-based cohort studies.SettingEurope, Asia-Pacific, and North AmericaParticipantsInfants, children, adolescents, and young adults born from 1984 to 2018, with mean ages at assessment of growth/adiposity outcomes ranging from 0.6 month to 27.4 years.ExposuresConception by ART (conventional in vitro fertilisation and intracytoplasmic sperm injection) versus natural conception (NC).Main Outcomes and MeasuresLength/height, weight, and body mass index (BMI). Each cohort was analysed separately with adjustment for maternal BMI, age, smoking, education, parity, ethnicity, and offspring sex and age. Cohort results were combined in random effects meta-analysis for thirteen age groups.ResultsUp to 158,066 offspring (4,329 conceived by ART) were included in each age-group meta-analysis; 47.6% to 60.6% were female. Compared with NC, ART-conceived offspring were slightly shorter, lighter, and thinner from infancy to early adolescence. The differences in growth/adiposity outcomes were largest at the youngest ages and attenuated with older child age, e.g., adjusted standardised mean differences (95% confidence intervals) in offspring weight at age ‘in vitro fertilisation and intracytoplasmic sperm injection however, smaller offspring size appeared to be limited to offspring conceived by fresh but not frozen embryo transfer, compared with NC. More marked but less precise differences were observed for body fat measurements. There was imprecise evidence that offspring conceived by ART may develop greater adiposity by early adulthood.Conclusions and RelevancePeople conceiving or conceived by ART can be reassured that differences in early growth and adiposity are small and no longer evident by late adolescence.KEY POINTSQuestionIs conception by assisted reproductive technology associated with growth and adiposity from infancy to early adulthood?FindingsIn this multi-cohort study of up to 158,066 European, Asian-Pacific, and Canadian infants, children, adolescents, and young adults, those conceived using assisted reproductive technology were on average shorter, lighter, and thinner from infancy up to early adolescence when compared with their naturally conceived peers though differences were small across all ages and reduced with older age.MeaningParents conceiving or hoping to conceive through assisted reproductive technology and their offspring should be reassured that differences in early life growth and adiposity are small and no longer apparent by late adolescence.

Several longitudinal studies investigated changes in mental health related to the pandemic event. However, little research has focused on the mediating role of environmental and genetic factors. The current prospective study aimed to evaluate the genetic and environmental contributions to the stability of symptoms of depression, anxiety and stress during the COVID-19 crisis. A total of 798 adult twins, previously enrolled in the Italian Twin Register, participated in the study and completed on-line questionnaires sent out on June 2020 and December 2020. The nine-item Patient Health Questionnaire (PHQ-9), the six-item State-Trait Anxiety Inventory (STAI-6), and the Impact of Event Scale - Revised (IES-R) were administered to assess depressive and anxiety symptoms, and pandemic-related subjective distress, respectively. A considerable longitudinal stability was observed for each trait (range: 0.57, STAI-6 - 0.67, PHQ-9). Bivariate Cholesky decomposition indicated that genetic factors explained from 53% (IES-R) to 61% (STAI-6) of between-wave covariance and that genetic overlap between the two waves was almost complete (range: 0.91, STAI-6 - 0.99, PHQ-9). Our findings support the hypothesis, at least over the 6-month period examined, of a genetic stability between waves and of an environmental discontinuity due to changes in life conditions during the pandemic.

No previous research explored the genetic and environmental structure of Big Five dimensions of personality and higher-order factors in a single twin study, except, in part, for just one study. We used the twin design to estimate the effects of genes and environment on both Five Factor model and related second- and third-order factors (i.e., Alpha [stability], Beta [plasticity], and GFP [general factor of personality]). We analyzed data from 314 adult twins (157 pairs: 83 monozygotic, 74 dizygotic; mean age: 52 years) enrolled in the Italian Twin Register. Participants underwent clinical and instrumental evaluations, and completed a 25-adjective list drawn from the Short Adjectives Checklist to Measure Big Five (SACBIF). We applied quantitative genetic models to unravel the sources of variation and covariation for the Big Five and higher-order factors. We found a similar etiological architecture across the different levels of analysis, with moderate to substantial non-additive genetic and unique environmental influences on all the personality traits, and no shared environmental contribution for any of them. We also detected significant genetic correlations for the Big Five dimensions and the Alpha and Beta super-factors. With some limitations, our results suggest that the etiological architecture of personality may be invariant to the factor level of analysis.

Italy, one of the first countries to be heavily hit by the spread of the new Coronavirus, has activated precautionary measures aimed at limiting its spread. This emergency situation may be cause of psychological distress in the general population. Therefore, the Italian Twins Registry has decided to carry out an epidemiological study to investigate the social and mental health impact of the covid-19 pandemic on Italian adults.The study has a longitudinal design and is aimed at twins of all ages residing in Italy. An online questionnaire was administered to collect information on socio-economic and health status of the participants, as well as of the households during the lockdown, and on the impact of the pandemic on participants' lives. Levels and prevalence of symptoms of anxiety, stress and depression were measured using validated instruments, such as the STAI-6, IES-R and PHQ-9. This article shows the results of the first wave of the survey (June 2020).A total of 2589 twins participated in the study, with a mean age of 45 years (range 18-93 years). Covid-19's prevalence among respondents was less than 1% and about 13% of the subjects reported that, at least, one of the household's members had symptoms of covid-19. Sixty percent of the participants changed the place and way of working and a third of the sample had to completely suspend their work. About half of the sample showed symptoms of an anxiety disorder and about 10% of the subjects had symptoms of a probable post-traumatic stress or depressive disorder. Higher mean scores on the three assessment instruments were observed among women, subjects with a low level of education and those residing in the Southern of Italy. Anxiety symptoms decreased with age.The study shows that the pandemic has had important repercussions on the socio-economic condition and mental health of the Italian population and suggests that some individuals are more vulnerable than others.

We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural-geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a(2)=0.43; 0.41-0.44), but also environmental variation shared by co-twins was substantial (c(2)=0.31; 0.30-0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900-1949 (a(2)=0.44; 0.41-0.46) than in the later cohorts born in 1950-1989 (a(2)=0.38; 0.36-0.40), with a corresponding lower influence of common environmental factors (c(2)=0.31; 0.29-0.33 and c(2)=0.34; 0.32-0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s. This study was conducted within the CODATwins project. We thank Wendy Cozen, University of Southern California, for sharing data with us. Funding for collaborators: Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192; VU University's Institute for Health and Care Research (EMGO+); the European Research Council (ERC - 230374), the Avera Institute, Sioux Falls, South Dakota (USA). Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE - European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, Grant Agreement Number 201413, National Institute of Alcohol Abuse and Alcoholism (Grants AA-12502, AA-00145, and AA-09203 to R J Rose, the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant Numbers: 213506, 129680), and the Academy of Finland (Grants 100499, 205585, 118555, 141054, 265240, 263278 and 264146 to J Kaprio). Since its origin the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium). Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. The Murcia Twin Registry is supported by Fundacion Seneca, Regional Agency for Science and Technology, Murcia, Spain (08633/PHCS/08, 15302/PHCS/10 & 19479/PI/14) and Ministry of Science and Innovation, Spain (PSI2009-11560 & PSI2014-56680-R). K Silventoinen is supported by Osaka University's International Joint Research Promotion Program. We acknowledge The Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no 2017-00641. This research was facilitated through access to Twins Research Australia, a national resource supported by a Centre of Research Excellence Grant (ID: 1079102), from the National Health and Medical Research Council. California Twin Program was supported by The California Tobacco-Related Disease Research Program (7RT-0134H, 8RT-0107H, 6RT-0354H) and the National Institutes of Health (1R01ESO15150-01). The Carolina African American Twin Study of Aging (CAATSA) was funded by a grant from the National Institute on Aging (grant 1RO1-AG13662-01A2) to K. E. Whitfield. Colorado Twin Registry is funded by NIDA funded center grant DA011015, & Longititudinal Twin Study HD10333; Author Huibregtse is supported by 5T32DA017637 and 5T32AG052371. Washington State Twin Registry (formerly the University of Washington Twin Registry) was supported in part by grant NIH RC2 HL103416 (D. Buchwald, PI). Vietnam Era Twin Study of Aging was supported by National Institute of Health grants NIA R01 AG018384, R01 AG018386, R01 AG022381, and R01 AG022982, and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA/NIH, or the VA. The NAS-NRC Twin Registry acknowledges financial support from the National Institutes of Health grant number R21 AG039572. Korean Twin-Family Register was supported by the Global Research Network Program of the National Research Foundation (NRF 2011-220-E00006). Osaka University Aged Twin Registry is supported by grants from JSPS KAKENHI JP (23593419, 24792601, 26671010, 24590695, 26293128, 16K15385, 16K15978, 16K15989, 16H03261).

Context Analysis of a 2-screen program for congenital hypothyroidism (CH) was performed using differential dried-blood spot thyrotropin (bTSH) cutoffs of 10 mU/L at first screening (all infants) and 5 mU/L at second screening (selected infants). Objectives This work aimed to characterize CH infants identified by the second screening and compare infants with bTSH of 5.0 to 9.9 and 10 mU/L or greater on second screening. Design and Patients Maternal and neonatal clinical features were retrospectively analyzed for 119 CH babies detected on the second screen in the Lombardy region of Italy, 2007 to 2014. Results Fifty-two (43.7%) of the 119 CH neonates showed bTSH values ranging from 5.0 to 9.9 mU/L at the second screening (low bTSH group) and 67 (56.3%) bTSH of 10.0 mU/L or greater (high bTSH group). The frequency of thyroid dysgenesis and eutopic gland was similar in both groups, as was the frequency of permanent and transient CH. Moreover, a high frequency of extrathyroidal malformations was found in both groups. The percentage of preterm infants (57.7% vs 23.9%, P Conclusions This study has demonstrated that a lower TSH cutoff at the second screening can detect additional cases of CH and that a second bTSH cutoff of 5.0 mU/L is appropriate for identifying preterm newborns and babies with associated risk factors.

Kaprio, Jaakko/0000-0002-3716-2455; Huibregtse, Brooke M./0000-0003-0977-7249; Magnusson, Patrik KE/0000-0002-7315-7899; ONCEL, Sevgi YURT/0000-0002-0990-292X; Aliev, Fazil/0000-0001-8357-4699; Silventoinen, Karri/0000-0003-1759-3079; van Beijsterveldt, Toos/0000-0002-6617-4201; Knafo-Noam, Ariel/0000-0003-0613-1960; Latvala, Antti/0000-0001-5695-117X; Loos, Ruth/0000-0002-8532-5087; Bartels, Meike/0000-0002-9667-7555; Sund, Reijo/0000-0002-6268-8117; Willemsen, Gonneke/0000-0003-3755-0236 WOS:000560040700031 PubMed: 32409744 Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis. Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) [340-2013-5867]; Stockholm County Council (ALF-projects)Stockholm County Council; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation; Swedish Asthma and Allergy Association's Research Foundation; Swedish Research CouncilSwedish Research Council [2017-00641]; Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO)Netherlands Organization for Scientific Research (NWO) [904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008]; European Research CouncilEuropean Research Council (ERC); Avera Institute, Sioux Falls, South Dakota (USA); KNAW Academy Professor Award [PAH/6635]; ENGAGE - European Network for Genetic and Genomic Epidemiology [201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Academy of FinlandAcademy of Finland [100499, 205585, 118555, 141054, 265240, 263278, 308248, 312073, 264146]; Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium); Cancer Research UKCancer Research UK [C1418/A7974]; European UnionEuropean Union (EU) [HEALTH-F4-2007-201413]; BioSHaRE EU [HEALTH-F4-2010-261433, POCI/DES/56834/2004]; Portuguese agency for research (The Foundation for Science and Technology [FCT]); Krkkale University Research Grant: KKU [2009/43]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; Osaka University's International Joint Research Promotion Program [R01 HD068435, R01 MH062375]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R21 AG039572]; California Twin Program; California Tobacco-Related Disease Research ProgramUniversity of California System [7RT-0134H, 8RT-0107H, 6RT-0354H]; Carolina African American Twin Study of Aging - National Institute on Aging [1RO1-AG13662-01A2, DA011015, 5T32DA017637, 5T32AG052371]; Michigan State University [R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01]; National Institute of Mental Health (NIMH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01-HD066040]; Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) [11-SPG-2518]; MSU Foundation - National Institute of Mental Health [R01 MH58354, AA023322, HD081437]; Vietnam Era Twin Study of Aging; National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIA R01 AG018384, R01 AG018386, R01 AG022381, R01 AG022982]; VA San Diego Center of Excellence for Stress and Mental Health; Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs; Global Research Network Program of the National Research Foundation [NRF 2011-220-E00006]; National Research Foundation of KoreaNational Research Foundation of Korea [NRF-371-2011-1 B00047]; West Japan Twins and Higher Order Multiple Births Registry [15H05105]; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science; Centre of Research Excellence Grant [1079102]; National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [240994]; [266592] This study was conducted within the CODATwins project (Academy of Finland #266592). The CATSS-Study is supported by the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework grant no 340-2013-5867, grants provided by the Stockholm County Council (ALF-projects), the Swedish Heart-Lung Foundation and the Swedish Asthma and Allergy Association's Research Foundation. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no 2017-00641. Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192; Amsterdam Public Health (APH); the European Research Council (ERC - 230374), the Avera Institute, Sioux Falls, South Dakota (USA) and the KNAW Academy Professor Award (PAH/6635) to DIB. Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE - European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to R J Rose, the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers: 213506, 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278, 308248, 312073 and 264146 to J Kaprio). Since its origin the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium). Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Data collection and research stemming from the Norwegian Twin Registry is supported, in part, from the European Union's Seventh Framework Programmes ENGAGE Consortium (grant agreement HEALTH-F4-2007-201413, and BioSHaRE EU (grant agreement HEALTH-F4-2010-261433). Madeira data comes from the following project: Genetic and environmental influences on physical activity, fitness and health: the Madeira family study Project reference: POCI/DES/56834/2004 Founded by the Portuguese agency for research (The Foundation for Science and Technology [FCT]). S.Y. oncel and F. Aliev are supported by Krkkale University Research Grant: KKU, 2009/43 and TUBITAK grant 114C117. K Silventoinen is supported by Osaka University's International Joint Research Promotion Program. The Boston University Twin Project is funded by grants (#R01 HD068435 #R01 MH062375) from the National Institutes of Health to K. Saudino. California Twin Program was supported by The California Tobacco-Related Disease Research Program (7RT-0134H, 8RT-0107H, 6RT-0354H) and the National Institutes of Health (1R01ESO15150-01). The Carolina African American Twin Study of Aging (CAATSA) was funded by a grant from the National Institute on Aging (grant 1RO1-AG13662-01A2) to K. E. Whitfield. Colorado Twin Registry is funded byNIDA funded center grant DA011015, & Longitudinal Twin Study HD10333; Author Huibregtse is supported by 5T32DA017637 and 5T32AG052371.; The Michigan State University Twin Registry has been supported by Michigan State University, as well as grants R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01 from the National Institute of Mental Health (NIMH), R01-HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD), and 11-SPG-2518 from the MSU Foundation. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the NICHD, or the National Institutes of Health. The University of Southern California Twin Study is funded by a grant from the National Institute of Mental Health (R01 MH58354). The Texas Twin Project is currently funded by grants AA023322 and HD081437 from the National Institutes of Health. Vietnam Era Twin Study of Aging was supported by National Institute of Health grants NIA R01 AG018384, R01 AG018386, R01 AG022381, and R01 AG022982, and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA/NIH, or the VA. The NAS-NRC Twin Registry acknowledges financial support from the National Institutes of Health grant number R21 AG039572. Korean Twin-Family Register was supported by the Global Research Network Program of the National Research Foundation (NRF 2011-220-E00006). South Korea Twin Registry is supported by National Research Foundation of Korea (NRF-371-2011-1 B00047). The West Japan Twins and Higher Order Multiple Births Registry was supported by Grant-in-Aid for Scientific Research (B) (grant number 15H05105) from the Japan Society for the Promotion of Science. This research was facilitated through access to Twins Research Australia, a national resource supported by a Centre of Research Excellence Grant (ID: 1079102), from the National Health and Medical Research Council. Longitudinal Israeli Study of Twins was funded by the Starting Grant no. 240994 from the European Research Council (ERC) to Ariel Knafo.

Background The mechanism underlying the association between personality profile and subclinical atherosclerosis is poorly understood. This study explores the association between personality, carotid atherosclerosis and arterial stiffness, and the contribution of genes and environment to this association. Methods Early atherosclerotic traits, including carotid intima-media thickness (CCA-IMT), aortic pulse wave velocity (PWVao) and heart rate, were assessed in 318 adult twins, who also completed a Big Five personality questionnaire. Using the co-twin control approach, the association between intra-pair differences in clinical and personality scores was assessed in dizygotic (DZ) and monozygotic (MZ) twins separately. Results An association between CCA-IMT and extroverted personality, as well as between PWVao and openness to experience was detected. The inverse association between CCA-IMT and extraversion was persistent in DZ and disappeared in MZ twins, suggesting genetic confounding. In contrast, the association between PWVao and openness to experience was of the same magnitude in DZ and MZ twins, thus surviving the adjustment for genetic and shared environmental factors. Conclusions This study highlights that the association between some psychological factors and cardiovascular traits may be partly explained by genetic factors. This result may provide support for the feasibility of prevention programs based on assessing familiarity for personality disorders to detect genetic risk for subclinical cardiovascular disease.

Background: The frequency of overweight (OW) and obese (OB) children has increased worldwide, particularly in economically developed countries. No studies have been conducted to verify whether the ...

Loos, Ruth J F/0000-0002-8532-5087; Huibregtse, Brooke M./0000-0003-0977-7249; Kandler, Christian/0000-0002-9175-235X; Hjelmborg, Jacob/0000-0001-9630-9149; mangino, massimo/0000-0002-2167-7470; Siribaddana, Sisira/0000-0001-5821-2557; Plomin, Robert/0000-0002-0756-3629; Latvala, Antti/0000-0001-5695-117X; Kaprio, Jaakko/0000-0002-3716-2455; Willemsen, Gonneke/0000-0003-3755-0236; Tan, Qihua/0000-0003-3194-0030; Pahlen, Shandell/0000-0003-0753-4155; Pedersen, Nancy/0000-0001-8057-3543; Haworth, Claire/0000-0002-8608-289X; Nistico, Lorenza/0000-0003-1805-6240; Skytthe, Axel/0000-0002-8629-4913; van Beijsterveldt, Toos/0000-0002-6617-4201; Rebato, Esther/0000-0003-1221-8501; Li, Lintao/0000-0002-0604-9660; Bartels, Meike/0000-0002-9667-7555; Silventoinen, Karri/0000-0003-1759-3079; Cunha Oliveira, Vinicius/0000-0002-8658-3774; Sund, Reijo/0000-0002-6268-8117; Sodemann, Morten/0000-0001-8992-2500; Rasmussen, Finn/0000-0001-7915-7809; Harden, Kathryn/0000-0002-1557-6737; Medda, Emanuela/0000-0003-4837-4549; Kyvik, Kirsten Ohm/0000-0003-2981-0245; Colodro Conde, Lucia/0000-0002-9004-364X WOS: 000517442200060 PubMed: 31364586 The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m(2)) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status. Academy of FinlandAcademy of Finland [266592, 100499, 205585, 118555, 141054, 265240, 263278, 264146]; Osaka University's International Joint Research Promotion Program; Centre of Research Excellence Grant from the National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [1079102]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 HD068435, R01 MH062375, 1R01ESO15150-01, R21 AG039572]; National Medical Research Council Research Fellowship; California Tobacco-Related Disease Research ProgramUniversity of California System [7RT-0134H, 8RT-0107H, 6RT-0354H]; National Institute on AgingUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [1RO1-AG13662-01A2]; Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) [340-2013-5867]; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation; Swedish Asthma and Allergy Association's Research Foundation; Special Fund for Health Scientific Research in the Public Welfare, China [201502006]; NIDAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA011015, HD10333]; National Program for Research Infrastructure 2007 from the Danish Agency for Science, Technology and Innovation; Research Council for Health and Disease; Velux Foundation; US National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01 AG08761]; Fund of Scientific Research, FlandersFWO; ENGAGE - European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007 [201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Cancer Research UKCancer Research UK [C1418/A7974]; W T Grant Foundation; University of London Central Research fund; Medical Research CouncilMedical Research Council UK (MRC) [G81/343, G120/635]; Economic and Social Research CouncilEconomic & Social Research Council (ESRC) [RES-000-22-2206]; Institute of Social Psychiatry [06/07-11]; Leverhulme Research FellowshipLeverhulme Trust [RF/2/RFG/2008/0145]; Goldsmiths, University of London; UK Medical Research CouncilMedical Research Council UK (MRC) [MR/M021475/1, G0901245]; National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01AG053217, RC2 HL103416]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81125007]; Global Research Network Program of the National Research Foundation [NRF 2011-220-E00006]; European Research Council (ERC)European Research Council (ERC) [240994]; Michigan State University; National Institute of Mental Health (NIMH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01, 1R01-MH118848-01]; Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) [R01-HD066040]; MSU Foundation [11-SPG-2518]; Fundacion Seneca, Regional Agency for Science and Technology, Murcia, Spain [08633/PHCS/08, 15302/PHCS/10, 19479/PI/14]; Ministry of Science and Innovation, SpainSpanish Government [PSI2009-11560, PSI2014-56680-R]; MagW/ZonMW [904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192]; European Research CouncilEuropean Research Council (ERC) [ERC-230374]; JSPS KAKENHI JP [23593419, 24792601, 26671010, 24590695, 26293128, 16K15385, 16K15978, 16K15989, 16H03261]; Australian National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [437015, 607358]; Bonnie Babes Foundation [BBF20704]; Financial Markets Foundation for Children [032-2007]; Victorian Government; Portuguese agency for research (The Foundation for Science and Technology [FCT]) [POCI/DES/56834/2004]; Wellcome TrustWellcome Trust; Medical Research CouncilMedical Research Council UK (MRC); European UnionEuropean Union (EU); National Institute for Health Research (NIHR)National Institute for Health Research (NIHR); King's College London; Fonds Quebecois de la Recherche sur la Societe et la CultureFQRNT; Fonds de la Recherche en Sante du QuebecFonds de la Recherche en Sante du Quebec; Social Science and Humanities Research Council of Canada; National Health Research Development Program; Canadian Institutes for Health ResearchCanadian Institutes of Health Research (CIHR); Sainte-Justine Hospital's Research Center; Canada Research Chair ProgramCanada Research Chairs; National Research Foundation of KoreaNational Research Foundation of Korea [NRF-371-2011-1 B00047]; Swedish Research CouncilSwedish Research Council [2017-00641]; UK Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC) [31/D19086]; MRCMedical Research Council UK (MRC) [MR/M021475/1]; Krkkale University [2009/43]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01 MH58354]; National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIA R01 AG018384, R01 AG018386, R01 AG022381, R01 AG022982]; VA San Diego Center of Excellence for Stress and Mental Health; Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [15H05105]; Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust; Stockholm County Council (ALF-projects)Stockholm County Council; Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium); [5T32DA017637]; [5T32AG052371] This study was conducted within the CODATwins project (Academy of Finland #266592). K Silventoinen is supported by Osaka University's International Joint Research Promotion Program. This research was facilitated through access to Twins Research Australia, a national resource supported by a Centre of Research Excellence Grant (ID: 1079102), from the National Health and Medical Research Council. The Boston University Twin Project is funded by grants (#R01 HD068435 #R01 MH062375) from the National Institutes of Health to K. Saudino. Paulo Ferreira is funded by a National Medical Research Council Research Fellowship. California Twin Program was supported by The California Tobacco-Related Disease Research Program (7RT-0134H, 8RT-0107H, 6RT-0354H) and the National Institutes of Health (1R01ESO15150-01).; The Carolina African American Twin Study of Aging (CAATSA) was funded by a grant from the National Institute on Aging (grant 1RO1-AG13662-01A2) to K. E. Whitfield. The CATSS-Study is supported by the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework grant no 340-2013-5867, grants provided by the Stockholm County Council (ALF-projects), the Swedish Heart-Lung Foundation and the Swedish Asthma and Allergy Association's Research Foundation.; Chinese National Twin Registry is funded by Special Fund for Health Scientific Research in the Public Welfare (Project No: 201502006), China. Colorado Twin Registry is funded by NIDA-funded center grant DA011015, & Longitudinal Twin Study HD10333; Author Huibregtse is supported by 5T32DA017637 and 5T32AG052371. Danish Twin Registry is supported by the National Program for Research Infrastructure 2007 from the Danish Agency for Science, Technology and Innovation, The Research Council for Health and Disease, the Velux Foundation and the US National Institute of Health (P01 AG08761). Since its origin, the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium). Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE - European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145 and AA-09203 to R J Rose, the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers: 213506, 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278 and 264146 to J Kaprio). Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Waves 1-3 of Genesis 12-19 were funded by the W T Grant Foundation, the University of London Central Research fund and a Medical Research Council Training Fellowship (G81/343) and Career Development Award (G120/635) to Thalia C. Eley. Wave 4 was supported by grants from the Economic and Social Research Council (RES-000-22-2206) and the Institute of Social Psychiatry (06/07-11) to Alice M. Gregory, who was also supported at that time by a Leverhulme Research Fellowship (RF/2/RFG/2008/0145). Wave 5 was supported by funding to Alice M. Gregory from Goldsmiths, University of London. T. C. Eley is partly funded by a program grant from the UK Medical Research Council (MR/M021475/1).; This study presents independent research [partly] funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Minnesota Twin Registry (MTR) acknowledges support from NIH grant R01AG053217. Guangzhou Twin Eye Study is supported by National Natural Science Foundation of China (grant #81125007). Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. Korean Twin-Family Register was supported by the Global Research Network Program of the National Research Foundation (NRF 2011-220-E00006). Longitudinal Israeli Study of Twins was funded by the Starting Grant no. 240994 from the European Research Council (ERC) to Ariel Knafo. The Michigan State University Twin Registry has been supported by Michigan State University, as well as grants R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01 and 1R01-MH118848-01 from the National Institute of Mental Health (NIMH), R01-HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) and 11-SPG-2518 from the MSU Foundation. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the NICHD or the National Institutes of Health. The Murcia Twin Registry is supported by Fundacion Seneca, Regional Agency for Science and Technology, Murcia, Spain (08633/PHCS/08, 15302/PHCS/10 & 19479/PI/14) and Ministry of Science and Innovation, Spain (PSI2009-11560 & PSI2014-56680-R). The NAS-NRC Twin Registry acknowledges financial support from the National Institutes of Health grant number R21 AG039572. Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192; VU University's Institute for Health and Care Research (EMGO+); the European Research Council (ERC-230374), the Avera Institute, Sioux Falls, South Dakota (USA). Osaka University Aged Twin Registry is supported by grants from JSPS KAKENHI JP (23593419, 24792601, 26671010, 24590695, 26293128, 16K15385, 16K15978, 16K15989, 16H03261). PETS was supported by grants from the Australian National Health and Medical Research Council (grant numbers 437015 and 607358 to JC, and RS), the Bonnie Babes Foundation (grant number BBF20704 to JMC), the Financial Markets Foundation for Children (grant no. 032-2007 to JMC), and by the Victorian Government's Operational Infrastructure Support Program.; Madeira data comes from the following project: Genetic and environmental influences on physical activity, fitness and health: the Madeira family study Project reference: POCI/DES/56834/2004 Founded by the Portuguese agency for research (The Foundation for Science and Technology [FCT]). TwinsUK receives funding from the Wellcome Trust, Medical Research Council and European Union.; TwinsUK and M. Mangino are supported by the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. The Quebec Newborn Twin Study acknowledges financial support from the Fonds Quebecois de la Recherche sur la Societe et la Culture, the Fonds de la Recherche en Sante du Quebec, the Social Science and Humanities Research Council of Canada, the National Health Research Development Program, the Canadian Institutes for Health Research, Sainte-Justine Hospital's Research Center, and the Canada Research Chair Program (Michel Boivin). South Korea Twin Registry is supported by National Research Foundation of Korea (NRF-371-2011-1 B00047). We acknowledge The Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no. 2017-00641.; The Twins Early Development Study (TEDS) is supported by a program grant (G0901245) from the UK Medical Research Council and the work on obesity in TEDS is supported in part by a grant from the UK Biotechnology and Biological Sciences Research Council (31/D19086). Currently TEDS is supported by MRC grant 'MR/M021475/1'. The Texas Twin Project is currently funded by grant R01HD083613 from the National Institutes of Health. S. Y. oncel and F. Aliev are supported by Krkkale University Research Grant: KKU, 2009/43 and TUBITAK grant 114C117. The University of Southern California Twin Study is funded by a grant from the National Institute of Mental Health (R01 MH58354). Washington State Twin Registry (formerly the University of Washington Twin Registry) was supported in part by grant NIH RC2 HL103416 (D. Buchwald, PI). Vietnam Era Twin Study of Aging was supported by National Institute of Health grants NIA R01 AG018384, R01 AG018386, R01 AG022381 and R01 AG022982, and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the NIA/NIH, or the VA. The West Japan Twins and Higher Order Multiple Births Registry was supported by Grant-in-Aid for Scientific Research (B) (grant number 15H05105) from the Japan Society for the Promotion of Science.

Traditional exposure studies provide valuable insights for epidemiology, toxicology, and risk assessment. Throughout their lives, individuals are exposed to thousands of stressors in the environment which are not static, but influenced by environmental, temporal, spatial, and even socio-demographic factors. Existing exposure studies have usually focused on specific stressors for a constrained period of time. In response, the concept of the exposome has been raised, which is defined as the totality of exposure experienced from conception until death. The EU FP7-ENVIRONMENT research project HEALS was launched with the aim of incorporating a series of novel technologies, data analysis, and modelling tools to efficiently support exposome studies in Europe. The authors have developed a framework of modelling tools for estimating the long-term external exposure of selected population groups to multiple stressors through different pathways. As the starting point, the stressors, including electromagnetic fields (EMF) and ultraviolet light (UV) through dermal uptake, phthalates (DEHP, DIDP, and DINP) through inhalation, as well as chromium, mercury, and lead through food intake, have been selected. The simulation for multiple stressors has been realised by developing a probabilistic model that integrates the micro-environment approach, time-activity patterns, and a life course trajectory model. The methodology has been applied to a selected sample of subjects enrolled in the Italian Twin Registry (ITR). The results show that long-term exposures to multiple stressors are affected by factors including age, gender, geographical location, and education level. The methods developed in this paper extended the temporal and spatial scales of exposure modelling in Europe. Moreover, the application of our methods provided a novel approach and crucial input data for future work on environment-wide association studies.

ObjectiveEvidence of the effects of long-term fine particulate matter (PM2.5) exposure on hypertension and blood pressure is limited for populations exposed to high levels of PM2.5. We aim to assess associations of long-term exposure to PM2.5 with hypertension prevalence and blood pressure, and further explore the subpopulation differences and effect modification by participant characteristics in these associations in China.MethodsWe analysed cross-sectional data from 883 827 participants aged 35–75 years in the China Patient-Centred Evaluative Assessment of Cardiac Events Million Persons Project. Data from the monitoring station were used to estimate the 1-year average concentration of PM2.5. The associations of PM2.5 exposure with hypertension prevalence and blood pressure were investigated by generalised linear models, with PM2.5 included as either linear or spline functions.ResultsThe 1-year PM2.5 exposure of the study population ranged from 8.8 to 93.8 µg/m3 (mean 49.2 µg/m3). The adjusted OR of hypertension prevalence related to a 10 μg/m3 increase in 1-year PM2.5 exposure was 1.04 (95% CI, 1.02 to 1.05). Each 10 μg/m3 increment in PM2.5 exposure was associated with increases of 0.19 mm Hg (95% CI, 0.10 to 0.28) and 0.13 mm Hg (95% CI, 0.08 to 0.18) in systolic blood pressure and diastolic blood pressure, respectively. The concentration–response curves for hypertension prevalence and systolic blood pressure showed steeper slopes at higher PM2.5 levels; while the curve for diastolic blood pressure was U-shaped. The elderly, men, non-current smokers and obese participants were more susceptible to the exposure of PM2.5.ConclusionsLong-term exposure to PM2.5 is associated with higher blood pressure and increased risk of hypertension prevalence. The effects of PM2.5 on hypertension prevalence become more pronounced at higher PM2.5 levels. These findings emphasise the need to reduce air pollution, especially in areas with severe air pollution.

To disentangle genetic and environmental influences on the development of femoral plaques using a population of adult twins. To evaluate the potential role of shared genetic and environmental factors in the co-occurrence of femoral and carotid plaques. The sample included 566 twins belonging to 164 monozygotic (MZ) and 119 dizygotic (DZ) twin pairs, who underwent peripheral arterial assessment by B-mode ultrasound in different centers. The variance in femoral plaques onset was due to genetic factors and the remaining 50% was explained by common (15%) and unique (35%) environmental factors. Findings on sidedness and number of femoral plaques indicated that also these traits were mainly under genetic control. No effect of common environment was found on plaques composition, and variability of this trait was explained by genetics (64%) and unique environment (36%). Covariation between the liabilities to carotid and femoral plaques was mainly attributed to shared genes (77%), with the remaining 23% explained by individual-specific environmental factors shared by the two districts. Inter-individual differences in plaque onset as well as in their number, sidedness and composition are mainly genetic in origin. The results on the cooccurrence of carotid and femoral plaque underline the genetic role in atherogenesis.

Increased telomerase expression has been implicated in the pathogenesis of lung cancer and, since the primary cause of lung cancer is smoking, an association between telomerase reactivation and tobacco smoke has been proposed. In this work an investigation has been performed to assess the relationship between tobacco smoke exposure and telomerase activity (TA) in peripheral blood mononuclear cells of healthy smokers. The methylation status of the catalytic subunit of telomerase hTERT was concurrently investigated to assess the possible association between epigenetic modifications of hTERT and TA. Besides, the association between smoke and telomere length (TL) has been evaluated. Healthy monozygotic twins with discordant smoking habits were selected as study population to minimize inter-individual differences because of demographic characteristics and genetic heterogeneity. Statistically significant higher values of TA and TL were observed in smokers compared to nonsmoker co-twins. The multivariate analysis of data showed, besides smoking habits (P = 0.02), an influence of gender (P = 0.006) and BMI (P = 0.001) on TA and a borderline effect of gender (P = 0.05) on TL. DNA methylation analysis, focused on 100 CpG sites mapping in hTERT, highlighted nine CpG sites differentially methylated in smokers. When co-twins were contrasted, selecting as variables the intra-twin difference in TA and hTERT DNA methylation, a statistically significant inverse correlation (P = 0.003) was observed between TA and DNA methylation at the cg05521538 site. In conclusion, these results indicate an association of tobacco smoke with TA and TL and suggest a possible association between smoke-induced epigenetic effects and TA in healthy smokers. Environ. Mol. Mutagen. 58:551–559, 2017. © 2017 Wiley Periodicals, Inc.

Poster: "ECR 2016 / C-2137 / Vertebral artery diameter and flow: nature or nurture " by: " A. D. Tarnoki 1, D. L. Tarnoki1, L. Littvay1, P. Lucatelli2, C. Fagnani2, C. Baracchini3, G. Pucci4, G. Schillaci4, M. A. Stazi2; 1Budapest/HU, 2Rome/IT, 3Padua/IT, 4Terni/IT"

To compare long-term clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PPCI) using radial and femoral arterial access. The present study was an observational cohort study of patients with STEMI treated consecutively with PPCI between 2004 and 2011 at a single centre. The primary end point was all-cause mortality at a median follow-up of 3 years. Among 2727 patients, 1600 (58.7%) underwent PPCI via the femoral route. The femoral group was older (64.7 vs. 61.7 years; P

Low doses of drugs delivered at close, regular intervals are increasingly being used to manage patients with different neoplasms. Despite the good tolerability, treatment-related adverse events still occur following metronomic protocols. The aim of this study was to retrospectively investigate whether polymorphisms of different genes involved in fluoropyrimidine metabolism and 5-fluorouracil (5-FU) degradation rate were associated with the outcome of a low-dose capecitabine schedule. Genotyping of DPYD IVS14+1 G>A, MTHFR C677T, and A1298C single-nucleotide polymorphisms was performed by pyrosequencing technology. A PCR technique was used for genotyping TYMS-TSER. Using peripheral blood mononuclear cells, we also evaluated the 5-FU degradation rate, which determines the net result of all the enzymatic transformation of 5-FU, in terms of the amount of drug consumed by the cells in a time unit. The association of these variables with clinical outcome was evaluated using multivariate logistic regression analysis. Eighty-four patients with metastatic gastrointestinal cancer, who had been treated with a low-dose fluoropyrimidine schedule, as a rescue therapy were included in the study. The TSER 2R/2R genotype was significantly associated with both hematologic (odds ratio=7.90, P=0.002) and gastrointestinal toxicity (odds ratio=3.24, P=0.009). Because DPYD IVS14 G>A single-nucleotide polymorphism was not observed in the cohort, it was excluded from the statistical analysis. No significant association was detected between clinical outcome and both MTHFR polymorphisms and the 5-FU degradation rate. In the advanced setting of cancer care, high attention should be paid toward avoiding toxicity and worsening of quality of life. Although metronomic chemotherapy is generally well tolerated, treatment toxicity nonetheless does occur. Our data suggest a possible role of the TSER 2R/2R polymorphism as a predictive marker of toxicity in patients treated with low-dose capecitabine.

The Italian Twin Registry (ITR), established in 2001, is a population-based registry of voluntary twins. To date, it consists of approximately 29,000 twins who gave their consent to participate in the studies proposed by the ITR research group. The database comprises 11,500 monozygotic and 16,700 dizygotic twins resident throughout the country and belonging to a wide age range (from 0 to 95 years, mean 36.8 years). This article provides an overview of the recruitment strategies along with the major phenotypes investigated during an 18 years’ research period. Over the years, several self-reported questionnaire data were collected, together with saliva/blood samples and measurements taken during in-person interviews or outpatient clinical examinations. Mental and behavioral phenotypes as well as atherosclerotic traits were studied in depth across different age groups. A birth cohort of twins was established and followed up. Novel research hypotheses are also being tested in ongoing projects. The ITR is involved in international studies in collaboration with other twin registries and represents a valuable resource for national and international research initiatives regarding a broad spectrum of health-related characteristics.

This study explores the association between sleep quality and emotional regulation, and investigates the genetic and environmental bases of this association.Three-hundred-eighty-two adolescent twins, from the Italian Twin Registry, and their parents filled the Youth Self-Report and Child Behavior Checklist questionnaires, from which the construct of Effortful Control (EC) was derived as a measure of emotional regulation. Twins were identified as "good" or "non-good" sleepers based on answers to the Sleep Disorders Questionnaire. EC levels were compared between same-sex sleep discordant twins.A significant association was detected between EC scores and sleep quality. When controlling for shared (fetal or early life) environmental factors and genetic background in the discordant twin analysis, this association weakened in dizygotic twins and disappeared in monozygotic twins.Results support the association between sleep quality and EC in adolescence; furthermore, they suggest that sleep quality and emotional regulation may depend on common genetic or environmental factors.

Numerous epidemiological studies have confirmed the negative influences of air pollutants on human health, where fine particles (PM2.5) and nitrogen dioxide (NO

Loos, Ruth J F/0000-0002-8532-5087; Kaprio, Jaakko/0000-0002-3716-2455; Huibregtse, Brooke M./0000-0003-0977-7249; de Freitas, Duarte Luis/0000-0001-6642-3370; Aliev, Fazil/0000-0001-8357-4699; Medda, Emanuela/0000-0003-4837-4549; Bartels, Meike/0000-0002-9667-7555; Latvala, Antti/0000-0001-5695-117X; Sund, Reijo/0000-0002-6268-8117; Rebato, Esther/0000-0003-1221-8501; Silventoinen, Karri/0000-0003-1759-3079; Aaltonen, Sari/0000-0002-2873-4263; Nistico, Lorenza/0000-0003-1805-6240; Knafo-Noam, Ariel/0000-0003-0613-1960; van Beijsterveldt, Toos/0000-0002-6617-4201; Harden, Kathryn/0000-0002-1557-6737; Willemsen, Gonneke/0000-0003-3755-0236; Pahlen, Shandell/0000-0003-0753-4155 WOS: 000465255700021 PubMed: 30950584 Objective The objective of this study was to analyze how parental education modifies the genetic and environmental variances of BMI from infancy to old age in three geographic-cultural regions. Methods A pooled sample of 29 cohorts including 143,499 twin individuals with information on parental education and BMI from age 1 to 79 years (299,201 BMI measures) was analyzed by genetic twin modeling. Results Until 4 years of age, parental education was not consistently associated with BMI. Thereafter, higher parental education level was associated with lower BMI in males and females. Total and additive genetic variances of BMI were smaller in the offspring of highly educated parents than in those whose parents had low education levels. Especially in North American and Australian children, environmental factors shared by co-twins also contributed to the higher BMI variation in the low education level category. In Europe and East Asia, the associations of parental education with mean BMI and BMI variance were weaker than in North America and Australia. Conclusions Lower parental education level is associated with higher mean BMI and larger genetic variance of BMI after early childhood, especially in the obesogenic macro-environment. The interplay among genetic predisposition, childhood social environment, and macro-social context is important for socioeconomic differences in BMI. Collaborative Project of Development of Anthropometrical Measures in Twins (Academy of Finland) [266592]; Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences Framework Grant [340-2013-5867]; Stockholm County Council (ALF projects)Stockholm County Council; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation; Swedish Asthma and Allergy Association's Research Foundation; Netherlands Organization for Scientific ResearchNetherlands Organization for Scientific Research (NWO); MagW/ZonMW [904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie-56-464-14192]; Vrije University's Institute for Health and Care Research; European Research Council (ERC)European Research Council (ERC) [230374]; Avera Institute, Sioux Falls, South Dakota; European Network for Genetic and Genomic Epidemiology (ENGAGE) [FP7-HEALTH-F4-2007, 201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Academy of FinlandAcademy of Finland [100499, 205585, 118555, 141054, 265240, 264146, 312073]; Fund of Scientific Research, FlandersFWO; Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium); Cancer Research UKCancer Research UK [C1418/A7974]; European Union's Seventh Framework Programmes ENGAGE Consortium [HEALTH-F4-2007-201413]; Biobank Standardization and Harmonization for Research Excellence in the European Union [HEALTH-F4-2010-261433]; Kirikkale UniversityKirikkale University [2009/43]; Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; Osaka University's International Joint Research Promotion Program; National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01HD068435, R01MH062375]; California Tobacco-Related Disease Research ProgramUniversity of California System [7RT-0134H, 8RT-0107H, 6RT-0354H]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R01ESO15150-01, AA023322, HD081437, R21AG039572]; National Institute on Aging (NIA)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [1R01AG13662-01A2]; National Institute on Drug AbuseUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA011015]; Longitudinal Twin Study grant [HD10333]; MSU; National Institute of Mental Health (NIMH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01MH081813, R01MH0820-54, R01MH092377-02, R21MH070542-01, R03MH63851-01]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [R01HD066040]; MSU Foundation [11-SPG-2518]; NIMHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01MH58354]; NIH/NIAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R01AG018384, R01AG018386, R01AG022381, R01AG022982]; VA San Diego Center of Excellence for Stress and Mental Health; Cooperative Studies Program of the Office of Research & Development of the US Department of Veterans Affairs (VA); Global Research Network Program of the National Research Foundation (NRF) [2011-220-E00006]; NRF of Korea [NRF-371-2011-1 B00047]; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [15H05105]; National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [1079102]; ERCEuropean Research Council (ERC) [240994]; [POCI/DES/56834/2004]; [5T32DA017637]; [5T32AG052371] This study was conducted within the Collaborative Project of Development of Anthropometrical Measures in Twins (Academy of Finland Grant 266592). Funding for individual collaborators is as follows. The Child and Adolescent Twin Study in Sweden is supported by the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences Framework Grant 340-2013-5867, grants provided by the Stockholm County Council (ALF projects), the Swedish Heart-Lung Foundation, and the Swedish Asthma and Allergy Association's Research Foundation. The Netherlands Twin Register acknowledges support from the Netherlands Organization for Scientific Research and MagW/ZonMW Grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, and Spinozapremie-56-464-14192; Vrije University's Institute for Health and Care Research; the European Research Council (ERC; grant 230374); and the Avera Institute, Sioux Falls, South Dakota. Data collection and analyses in Finnish twin cohorts have been supported by the European Network for Genetic and Genomic Epidemiology (ENGAGE; FP7-HEALTH-F4-2007, grant agreement 201413), the National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to R. J. Rose), the Academy of Finland Center of Excellence in Complex Disease Genetics (grants 213506 and 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 264146, and 312073 to J. Kaprio). Since its origin, the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium). Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Data collection and research stemming from the Norwegian Twin Registry are supported, in part, by the European Union's Seventh Framework Programmes ENGAGE Consortium (grant agreement HEALTH-F4-2007-201413) and Biobank Standardization and Harmonization for Research Excellence in the European Union (grant agreement HEALTH-F4-2010-261433). Madeira data come from Genetic and Environmental Influences on Physical Activity, Fitness and Health: the Madeira Family Study (project reference: POCI/DES/56834/2004, founded by the Portuguese agency for research [the Foundation for Science and Technology]). S. Y. Oncel and F. Aliev are supported by a Kirikkale University research grant (2009/43) and a Scientific and Technological Research Council of Turkey grant (114C117). K. Silventoinen is supported by Osaka University's International Joint Research Promotion Program. The Boston University Twin Project is funded by grants (R01HD068435 and R01MH062375) from the National Institutes of Health (NIH) to K. J. Saudino. The California Twin Program was supported by the California Tobacco-Related Disease Research Program (7RT-0134H, 8RT-0107H, and 6RT-0354H) and NIH (1R01ESO15150-01). The Carolina African American Twin Study of Aging was funded by a grant from the National Institute on Aging (NIA; 1R01AG13662-01A2) to K. E. Whitfield. The Colorado Twin Registry is funded by National Institute on Drug Abuse grant DA011015 and Longitudinal Twin Study grant HD10333; B. M. Huibregtse is supported by 5T32DA017637 and 5T32AG052371.; The Michigan State University (MSU) Twin Registry has been supported by MSU, as well as by grants R01MH081813, R01MH0820-54, R01MH092377-02, R21MH070542-01, and R03MH63851-01 from the National Institute of Mental Health (NIMH), grant R01HD066040 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and grant 11-SPG-2518 from the MSU Foundation. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of NIMH, NICHD, or NIH. The University of Southern California Twin Study is funded by a grant from NIMH (R01MH58354). The Texas Twin Project is currently funded by grants AA023322 and HD081437 from NIH. The Vietnam Era Twin Study of Aging was supported by NIH/NIA grants R01AG018384, R01AG018386, R01AG022381, and R01AG022982 and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the US Department of Veterans Affairs (VA) has provided financial support for the development and maintenance of the Vietnam Era Twin Registry. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of NIA/NIH or VA. The National Academy of Sciences-National Research Council Twin Registry acknowledges financial support from NIH grant R21AG039572. The Korean TwinFamily Register was supported by the Global Research Network Program of the National Research Foundation (NRF; 2011-220-E00006). The South Korea Twin Registry is supported by the NRF of Korea (NRF-371-2011-1 B00047). The West Japan Twins and Higher Order Multiple Births Registry was supported by a Grant-inAid for Scientific Research (B) (15H05105) from the Japan Society for the Promotion of Science. This research was facilitated through access to Twins Research Australia, a national resource supported by a Centre of Research Excellence Grant (1079102) from the National Health and Medical Research Council. The Longitudinal Israeli Study of Twins was funded by Starting Grant 240994 from the ERC to A. Knafo-Noam.

ContextNewborn screening program for congenital hypothyroidism (CH) adopting rescreening in at-risk neonates.ObjectivesTo estimate the concordance rate for CH in twin pairs discordant at the first screening; to verify whether long-term follow-up of healthy cotwins belonging to CH discordant pairs may be useful to diagnose thyroid hypofunction during development; to evaluate the importance of genetic and environmental influences on liability to permanent and transient CH.Design and PatientsForty-seven screening discordant twin pairs were investigated. Proband was defined as the twin in the pair with a positive test at the first screening and a confirmed diagnosis of CH.ResultsSeven screening discordant twin pairs became concordant for CH within the first month of life (pairwise concordance of 14.9%) because seven screening negative cotwins showed high TSH values when retested. During long-term follow-up (range, 3 to 21 years), hypothyroidism was diagnosed in two monozygotic screening negative cotwins at the age of 9 months and 12 years, respectively. Furthermore, the twin analysis showed that 95% of liability to transient CH was explained by genetic factors and 5% by environmental (unshared) factors, whereas 64% of phenotypic variance of permanent CH was explained by common environmental factors (shared during the fetal life) and 36% by unshared environmental factors.ConclusionsThis study showed that the introduction of rescreening permits the diagnosis of CH in a greater number of twins. It also showed the importance of long-term follow-up in both twins in the pair, and the role of nongenetic factors in the etiology of permanent CH.

We compared intima–media thickness (IMT) and the prevalence of plaques in the common carotid artery (CCA) and common femoral artery (CFA) in apparently healthy participants. This multicenter study included 322 participants (59.9% female; age 20-78 years, mean 52.1 ± 15.3 years) who underwent Echo-color Doppler examination of the CCA and CFA bilaterally. Prevalence and composition of plaque were recorded. A significant ( P < .01) difference between mean CCA-IMT and mean CFA-IMT was detected (0.70 vs 0.73 mm). Plaque prevalence was significantly higher in the CFA compared to the CCA (40.7% vs 30.4%). Atherosclerotic plaques were found in both CFA and CCA in 46% of the cases, solely in CFA in 38%, and in CCA alone in 17%. The observed difference in plaque prevalence was even greater when only fibrolipid isolated plaques were considered (CFA 39.4% vs CCA 22.1%). In a healthy general population, atherosclerotic plaques were present in the CFA but not in the CCA in over one-third of the cases. Further studies must confirm whether ultrasonography of the CFA might be introduced in the screening protocols for cardiovascular risk assessment.

Background: Anatomic variants of the circle of Willis (CW) are commonly observed in healthy subjects. Genetic and environmental factors influencing these variants remain unclear. Our aim was to assess the genetic and environmental background affecting variant CW phenotypes. Methods: A total of 122 adult healthy twins from the Hungarian Twin Registry (39 monozygotic (MZ) and 22 dizygotic (DZ) pairs, average age 49.7 ± 13.4 years) underwent Time-of-Flight magnetic resonance angiography and transcranial Doppler sonography. We investigated the anterior and posterior CW according to morphological categories. Prevalence and concordance rates of CW variants were calculated. MZ twins discordant for CW variants were analyzed for cardiovascular risk factors and altered blood flow. Results: Complete CW (45.0%) and bilaterally absent posterior communicating artery (PCoA) (22.5%) were the most prevalent variants in the anterior and posterior CW, respectively. There was no significant difference regarding the prevalence of variants across zygosity except for bilaterally hypoplastic PCoA (p = .02). DZ concordance was higher compared to MZ twins regarding morphological categories of the CW. Cardiovascular risk factors were not significantly associated with variant CW in MZ twins discordant to CW morphology. Flow parameters did not differ significantly among MZ twins discordant to CW variants. Conclusion: CW variants may not be determined by substantial genetic effects and are not influenced by altered blood flow in healthy individuals. Further investigations are needed to identify potential environmental factors affecting these variants.

Numerous epidemiological studies have confirmed the negative influences of air pollutants on human health, where fine particles (PM2.5) and nitrogen dioxide (NO2) cause the highest health risks. However, the traditional studies have only involved the ambient concentration for a short to medium time period, which ignores the influence of indoor sources, the individual time-activity pattern, and the fact that the health status is impacted by the long-term accumulated exposure. The aim of this paper is to develop a methodology to simulate the lifelong exposure (rather than outdoor concentration) to PM2.5 and NO2 for individuals in Europe. This method is realized by developing a probabilistic model that integrates an outdoor air quality model, a model estimating indoor air pollution, an exposure model, and a life course trajectory model for predicting retrospectively the employment status. This approach has been applied to samples of two population studies in the frame of the European Commission FP7-ENVIRONMENT research project HEALS (Health and Environment-wide Associations based on Large Population Surveys), where socioeconomic data of the participants have been collected. Results show that the simulated exposures to both pollutants for the samples are influenced by socio-demographic characteristics, including age, gender, residential location, employment status and smoking habits. Both outdoor concentrations and indoor sources play an important role in the total exposure. Moreover, large variances have been observed among countries and cities. The application of this methodology provides valuable insights for the exposure modelling, as well as important input data for exploring the correlation between exposure and health impacts.

Carotid atherosclerosis (CAS) is associated with increased cardiovascular risk, and therefore, assessing the genetic versus environmental background of CAS traits is of key importance. Carotid intima-media-thickness and plaque characteristics seem to be moderately heritable, with remarkable differences in both heritability and presence or severity of these traits among ethnicities. Although the considerable role of additive genetic effects is obvious, based on the results so far, there is an important emphasis on non-shared environmental factors as well. We aimed to collect and summarize the papers that investigate twin and family studies assessing the phenotypic variance attributable to genetic associations with CAS. Genes in relation to CAS markers were overviewed with a focus on genetic association studies and genome-wide association studies. Although the role of certain genes is confirmed by studies conducted on large populations and meta-analyses, many of them show conflicting results. A great focus should be on future studies elucidating the exact pathomechanism of these genes in CAS in order to imply them as novel therapeutic targets.

Morphological and hemodynamic variations of the circle of Willis (CW) may have an important impact on cerebrovascular events. However, the environmental and genetic influence remains unclear. For this reason we studied the variations and hemodynamic parameters of the CW in twins using transcranial color-coded sonography (TCCS). Sixty-four twins, 19 monozygotic (MZ) and 13 dizygotic (DZ) pairs from the Italian Twin Registry (average age 45.0 ± 13.7 years) underwent TCCS and risk factor assessment. We examined CW morphology and recorded peak systolic velocity (PSV), end-diastolic velocity (EDV) and pulsatility index (PI). Raw heritability was determined for hemodynamic parameters, whereas concordance and discordance rates were calculated for CW morphological variants. A normal CW anatomy was observed in the majority of MZ and DZ twins (76.5% and 92.3%, respectively). The most frequent variant was a missing anterior cerebral artery (ACA). There was no significant difference in the prevalence of most CW variants depending on the zigosity. Concordance rates were low regarding the presence of variant CW anatomy both in MZ and DZ groups (0.14 and 0.00, respectively). Women had a significantly higher PI in vertebral arteries (VA) and in the right ACA (p = 0.01, p = 0.02 and p

Aims The elasticity of the internal jugular vein (IJV) is a major determinant of cerebral venous drainage and right atrium venous return. However, the level of genetic determination of IJV dimensions, compliance and distensibility has not been studied yet. Methods 170 adult Caucasian twins (43 monozygotic [MZ] and 42 dizygotic [DZ] pairs) were involved from the Italian twin registry. Anteroposterior and mediolateral diameters of the IJV were measured bilaterally by ultrasonography. Measurements were made both in the sitting and supine positions, with or without Valsalva maneuver. Univariate quantitative genetic modeling was performed. Results Genetic factors are responsible for 30-70% of the measured properties of IJV at higher venous pressure even after adjustment for age and gender. The highest level of inheritance was found in the supine position regarding compliance (62%) and venous diameter during Valsalva (69%). Environmental and measurement-related factors instead are more important in the sitting position, when the venous pressure is low and the venous lumen is almost collapsed. The range of capacity changes between the lowest and highest intraluminal venous pressure (full distension range) are mainly determined by genetic factors (58%). Conclusions Our study has shown substantial heritability of IJV biomechanics at higher venous pressures even after adjustment for age and gender. These findings yield an important insight to what degree the geometric and elastic properties of the vascular wall are formed by genetic and by environmental factors in humans.

Background We aimed at evaluating the impact of genetic and environmental factors on longitudinal changes in aortic pulse wave velocity (aPWV) and aortic augmentation index (aAIx). Method Three hundred and sixty-eight Italian and Hungarian adult twins (214 monozygotic, 154 dizygotic) underwent repeated evaluations of aPWV and aAIx (TensioMed Arteriograph). Within-individual/cross-wave, cross-twin/within-wave and cross-twin/cross-wave correlations were calculated; bivariate Cholesky models were fitted to calculate additive genetic (A), shared environmental (C) and unique environmental (E) components. Results For both aPWV and aAIx, cross-twin correlations in monozygotic pairs (r between 0.35 and 0.56) were all significant and always higher than in dizygotic pairs, both at wave 1 and at wave 2. Heritability and unshared environmental proportion of variance at each wave were substantially time-invariant for aPWV (heritability 0.51, 95% CI 0.36-0.63 at wave 1; 0.49, 95% CI 0.34-0.62 at wave 2), whereas for aAIx, we observed a diminished genetic effect (heritability 0.57, 95% CI 0.45-0.67 at wave 1; 0.37, 95% CI 0.21-0.51 at wave 2). Overlapping genetic factors explained a high proportion (0.88, 95% CI 0.61-1.00) of longitudinal covariance for aPWV, and had a relatively lower impact on aAIx (0.55, 95% CI 0.35-0.70). Genetic correlations of aPWV (r = 0.64, 95% CI 0.42-0.85) and aAIx (r = 0.70, 95% CI 0.52-0.87) between waves were lower than 1, suggesting a potential contribution of novel genetic variance on arterial stiffening. Conclusion Changes in aPWV and aAIx over time are largely genetically determined. Our results might stimulate further studies on genetic and epigenetic factors influencing the process of vascular ageing.

The role of genes and environment in the relation between self-regulation and adjustment is unclear. We investigated, with the twin design, genetic and environmental components of the association between effortful control (EC) and indicators of psychological adjustment using adolescents’ and parents’ reports for 774 twins. Genetic factors explained a substantial proportion of variance in EC (58%) and the outcome variables of optimism (55%), general self-esteem (45%), happiness (48%), and self-derogation (29%). Perceived competence had no significant genetic component. Aside from perceived competence, uncorrelated with EC, phenotypic correlations of EC with measures of well-being/adjustment were moderate and predominantly explained by shared genetic effects. Results suggest a significant genetic contribution in adolescents’ EC and in its relation to various aspects of adjustment.

Background The measurement of femoral intima-media thickness (IMT) is underutilized in the clinical practice, although it is a surrogate marker of cardiovascular disease. Materials and methods 388 Hungarian and Italian twins (121 monozygotic, 73 dizygotic pairs) underwent bilateral B-mode sonography of femoral arteries. IMT was measured by semiautomated software, where available, or by calipers. Results Within-pair correlation in monozygotic twins was higher than in dizygotics for each parameter. Age-, sex- and country-adjusted genetic effect accounted for 43.9% (95% confidence interval, CI 21.3%–65.2%) and 47.2% (95% CI, 31.4%–62.6%) of the variance of common and superficial femoral artery IMT, respectively, and unshared environmental effect for 56.1% (95% CI 34.6%–78.5%) and 52.8% (95% CI, 37.2%–68.5%). These results did not change significantly after correcting for body mass index or central systolic blood pressure. Conclusions Genetic factors have a moderate role in the determination of common and superficial femoral IMT; however, the influence of environmental (lifestyle) factors remains still relevant. Environmental factors may have a role in influencing the genetic predisposition for femoral vascular hypertrophy.