Attitude and concerns of healthy individuals regarding post-mortem brain donation. A qualitative study on a nation-wide sample in Italy.

BACKGROUND: Collecting post-mortem brain tissue is essential, especially from healthy "control" individuals, to advance knowledge on increasingly common neurological and mental disorders. Yet, healthy individuals, on which this study is focused, are still understudied. The aim of the study was to explore, among healthy potential brain donors and/or donors' relatives, attitude, concerns and opinion about post-mortem brain donation (PMBD). METHODS: A convenience sampling of the general population (twins and their non-twin contacts) was adopted. From June 2018 to February 2019, 12 focus groups were conducted in four Italian cities: Milan, Turin, Rome and Naples, stratified according to twin and non-twin status. A qualitative content analysis was performed with both deductive and inductive approaches. Emotional interactions analysis corroborated results. RESULTS: One hundred and three individuals (49-91 yrs of age) participated. Female were 60%. Participants had scarse knowledge regarding PMBD. Factors affecting attitude towards donation were: concerns, emotions, and misconceptions about donation and research. Religion, spirituality and secular attitude were implied, as well as trust towards research and medical institutions and a high degree of uncertainty about brain death ascertainment. Family had a very multifaceted central role in decision making. A previous experience with neurodegenerative diseases seems among factors able to favour brain donation. CONCLUSIONS: The study sheds light on healthy individuals' attitudes about PMBD. Brain had a special significance for participants, and the ascertainment of brain death was a source of debate and doubt. Our findings emphasise the importance of targeted communication and thorough information to promote this kind of donation, within an ethical framework of conduct. Trust in research and health professionals emerged as an essential factor for a collaborative attitude towards donation and informed decision making in PMBD.

Age-Related Variations of Genetic and Environmental Contributions to the Covariation of Fear, Distress and Externalizing Symptoms: A Twin Study in Childhood and Adolescence.

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.

Prenatal exposure to PM10 and changes in DNA methylation and telomere length in cord blood.

BACKGROUND: Air pollution exposure in pregnancy can cause molecular level alterations that might influence later disease susceptibility. OBJECTIVES: We investigated DNA methylation (DNAm) and telomere length (TL) in the cord blood in relation to gestational PM10 exposure and explored potential gestational windows of susceptibility. METHODS: Cord blood epigenome-wide DNAm (N = 384) and TL (N = 500) were measured in children of the Italian birth cohort Piccolipiù, using the Infinium Methylation EPIC BeadChip and qPCR, respectively. PM10 daily exposure levels, based on maternal residential address, were estimated for different gestational periods using models based on satellite data. Epigenome-wide analysis to identify differentially methylated probes (DMPs) and regions (DMRs) was conducted, followed by a pathway analysis and replication analysis in an second Piccolipiù dataset. Distributed lag models (DLMs) using weekly exposures were used to study the association of PM10 exposure across pregnancy with telomere length, as well as with the DMPs that showed robust associations. RESULTS: Gestational PM10 exposure was associated with the DNA methylation of more than 250 unique DMPs, most of them identified in early gestation, and 1 DMR. Out of 151 DMPs available in the replication dataset, ten DMPs showed robust associations: eight were associated with exposure during early gestation and 2 with exposure during the whole pregnancy. These exposure windows were supported by the DLM analysis. The PM10 exposure between 15th and 20th gestational week seem to be associated with shorter telomeres at birth, while exposure between 24th and 29th was associated with longer telomeres. DISCUSSION: The early pregnancy period is a potential critical window during which PM10 exposure can influence cord blood DNA methylation. The results from the TL analysis were consistent with previous findings and merit further exploration in future studies. The study underlines the importance of considering gestational windows outside of the predefined trimesters that may not always overlap with biologically relevant windows of exposure.

An Italian Twin Study of Non-Cancer Chronic Pain as a Wide Phenotype and Its Intensity.

Background and Objectives: Non-cancer chronic pain (CP) results from the interaction between genetic and environmental factors. Twin studies help to estimate genetic and environmental contributions to complex traits such as CP. To date, twin studies on the heritability of pain phenotypes have relied almost exclusively on specific diagnoses, neglecting pain intensity. This study aims to estimate the genetic and environmental contributions to CP occurrence as a wide phenotype and its intensity among a non-clinical population. Materials and Methods: A nationwide online survey was conducted in February 2020 on 6000 adult twins enrolled in the Italian Twin Registry. A five-item questionnaire, designed and validated by our study group, was administered to detect the CP condition along with its intensity, underlying causes or triggers, treatments, and self-perceived efficacy. The twin study design was used to infer the relative weight of genes and environment on CP occurrence and intensity, and biometrical modelling was applied to these phenotypes. Results: A total of 3258 twins, aged ≥18, replied to the online survey (response rate 54%). These included 762 intact pairs (mean age: 39 years; age range: 18-82 years; 34% male; CP prevalence: 24%), of whom 750 pairs were subjected to biometrical modelling after the exclusion of pairs with either unknown zygosity or cancer-associated CP. Broad-sense heritability estimates were driven by non-additive genetic effects and were 0.36 (0.19-0.51) for CP occurrence and 0.31 (0.16-0.44) for CP intensity. No evidence emerged for either sex differences in genetic and environmental variance components or interactions of these components with age. Conclusions: Moderate non-additive genetic components were suggested for non-cancer CP occurrence and its intensity. These results encourage further research on the gene-gene interactions underlying CP liability and associated phenotypes, and also strengthen the need for prevention strategies to avoid CP occurrence or to decrease pain intensity.

Exposure to ambient air pollution in the first 1000 days of life and alterations in the DNA methylome and telomere length in children: A systematic review.

BACKGROUND: Exposure to air pollution during the first 1000 days of life (from conception to the 2nd year of life) might be of particular relevance for long-term child health. Changes in molecular markers such as DNA methylation and telomere length could underlie the association between air pollution exposure and pollution-related diseases as well as serve as biomarkers for past exposure. The objective of this systematic review was to assess the association between air pollution exposure during pregnancy and the first two years of life and changes in DNA methylation or telomere length in children. METHODS: PubMed was searched in October 2020 by using terms relative to ambient air pollution exposure, DNA methylation, telomere length and the population of interest: mother/child dyads and children. Screening and selection of the articles was completed independently by two reviewers. Thirty-two articles matched our criteria. The majority of the articles focused on gestational air pollution exposure and measured DNA methylation/telomere length in newborn cord blood or placental tissue, to study global, candidate-gene or epigenome-wide methylation patterns and/or telomere length. The number of studies in children was limited. RESULTS: Ambient air pollution exposure during pregnancy was associated with global loss of methylation in newborn cord blood and placenta, indicating the beginning of the pregnancy as a potential period of susceptibility. Candidate gene and epigenome-wide association studies provided evidence that gestational exposure to air pollutants can lead to locus-specific changes in methylation, in newborn cord blood and placenta, particularly in genes involved in cellular responses to oxidative stress, mitochondrial function, inflammation, growth and early life development. Telomere length shortening in newborns and children was seen in relation to gestational pollutant exposure. CONCLUSIONS: Ambient air pollution during pregnancy is associated with changes in both global and locus-specific DNA methylation and with telomere length shortening. Future studies need to test the robustness of the association across different populations, to explore potential windows of vulnerability and assess the role of the methylation and telomere length as mediators in the association between early exposure to ambient air pollutants and specific childhood health outcomes.

The role of genetic and environmental factors in covariation between anxiety and anger in childhood.

Higher levels of anger expression, as well as lower levels of anger control, have been reported for adults with anxiety disorders compared to individuals without anxiety disorders. Different to the research on adults, very few studies examined the relationship between anxiety and anger in childhood. In our study, we investigated 398 Italian twin pairs (74 MZ male, 70 MZ female, 134 same-sex dizygotic-53 male, 81 female-, and 120 unlike-sex dizygotic twin pairs), aged 8-17 (mean 13.06 ± 2.59): (i) the heritability of a childhood anger phenotype; (ii) the association between five anxiety domains and anger; (iii) the role of possible common etiological factors in explaining the observed comorbidity and overlap in the risk between anxiety phenotypes and anger. The study demonstrated that anger, assessed by CBCL items, is heritable in children at a similar rate to prior studies (40%). Our research found low to moderate rate of correlation between anger and anxiety (from 0.10 to 0.19). Finally, the present study found that the majority of etiological influences on anxiety and anger are independent of each other. Data showed that shared environmental influences have some small effects on the phenotypic covariation between the anxiety phenotypes and anger (12%); whereas unique environmental influences have an almost negligible effect (1%). Our analyses did not reveal the effect of genetic effects in explaining the covariation between these phenotypes.

Influence of residential land cover on childhood allergic and respiratory symptoms and diseases: Evidence from 9 European cohorts.

INTRODUCTION: Recent research focused on the interaction between land cover and the development of allergic and respiratory disease has provided conflicting results and the underlying mechanisms are not fully understood. In particular, green space, which confers an overall positive impact on general health, may be significantly contributing to adverse respiratory health outcomes. This study evaluates associations between surrounding residential land cover (green, grey, agricultural and blue space), including type of forest cover (deciduous, coniferous and mixed), and childhood allergic and respiratory diseases. METHODS: Data from 8063 children, aged 3-14 years, were obtained from nine European population-based studies participating in the HEALS project. Land-cover exposures within a 500 m buffer centred on each child's residential address were computed using data from the Coordination of Information on the Environment (CORINE) program. The associations of allergic and respiratory symptoms (wheeze, asthma, allergic rhinitis and eczema) with land coverage were estimated for each study using logistic regression models, adjusted for sex, age, body mass index, maternal education, parental smoking, and parental history of allergy. Finally, the pooled effects across studies were estimated using meta-analyses. RESULTS: In the pooled analyses, a 10% increase in green space coverage was significantly associated with a 5.9%-13.0% increase in the odds of wheezing, asthma, and allergic rhinitis, but not eczema. A trend of an inverse relationship between agricultural space and respiratory symptoms was observed, but did not reach statistical significance. In secondary analyses, children living in areas with surrounding coniferous forests had significantly greater odds of reporting wheezing, asthma and allergic rhinitis. CONCLUSION: Our results provide further evidence that exposure to green space is associated with increased respiratory disease in children. Additionally, our findings suggest that coniferous forests might be associated with wheezing, asthma and allergic rhinitis. Additional studies evaluating both the type of green space and its use in relation to respiratory conditions should be conducted in order to clarify the underlying mechanisms behind associated adverse impacts.

Perinatal maternal mental health is associated with both infections and wheezing in early childhood.

BACKGROUND: Wheezing and infections are common during infancy, and the role of early-life exposures in their development is still under investigation. We examined associations between maternal mental health in pregnancy and after delivery and subsequent offspring wheezing and infections. METHODS: We studied 2314 mother-child pairs recruited in the Piccolipiù birth cohort (Italy) from 2011 to 2015. Maternal mental health was assessed in pregnancy and 12 months after delivery via the General Health Questionnaire-12 (GHQ-12). GHQ-12 Likert scores were collapsed into low (below the upper tercile) and high (above). Risk ratios (RR) and 95% confidence intervals (CI) between each combination of scores-during pregnancy and 1 year after delivery-and outcomes were computed by log-binomial regression models. RESULTS: High scores both in pregnancy and after delivery, compared with low scores in both periods, were associated with wheezing (RR: 1.35; 95% CI: 1.08, 1.69), recurrent (≥2 episodes) wheezing (1.35; 0.99, 1.83), any and recurrent (≥4 episodes) upper respiratory infections (1.20; 1.04, 1.41, and 1.45; 1.07, 1.97, respectively), lower respiratory infections (1.31; 1.08, 1.61), and diarrhea (1.49; 1.23, 1.80). High scores either during pregnancy or 1 year after delivery only were less consistently associated with outcomes. CONCLUSIONS: Maternal mental health problems extending from pregnancy to the first year after delivery are associated with development of both wheezing and infections. As wheezing is mostly triggered by infections, increased infection susceptibility could represent a possible common biologic mechanism. This study confirms the importance of early-life exposures on childhood health.

Lifelong exposure to multiple stressors through different environmental pathways for European populations.

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.

The Italian Twin Registry: An Update at 18 Years From Its Inception.

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.

Adult Empathy: Possible Gender Differences in Gene-Environment Architecture for Cognitive and Emotional Components in a Large Italian Twin Sample.

Empathy plays a central role in prosocial behavior and human cooperation. Very few twin researchers have investigated innate and environmental effects in adult empathy, and twin research on gender differences in these effects is sparse. The goal of this study was to examine innate and environmental influences on three components of an empathy scale frequently used with adults - the expression of cognitive (CE), emotional (EE), and social skills (SS) empathy - and to explore gender differences in the influences. Study participants were ~1,700 twins (18-65 years) enrolled in the Italian Twin Registry. Empathy was assessed with the Italian version of the Empathy Quotient (EQ), for which the three-factor structure (i.e., CE, EE, and SS) was confirmed. Twin correlations in monozygotic and dizygotic pairs, and males and females were estimated for the total EQ and subscale scores, and univariate genetic model fitting was carried out. Women's empathy (i.e., total EQ as well as CE and EE subdimensions) was predominantly driven by genetic factors and individual experiences, whereas for males, no genetic contribution or important shared and individual environmental effects emerged. Although of large magnitude, the gender differences did not reach statistical significance. Age did not moderate empathy heritability in adulthood. Only for the SS subscale were genetic and environmental proportions of variance similar for men and women. This study suggests possible gender-specific innate and environmental influences on empathy and its cognitive and emotional components that need to be confirmed in future studies.

Lessons learned from twins in autoimmune and chronic inflammatory diseases.

Autoimmunity and chronic inflammation recognize numerous shared factors and, as a result, the resulting diseases frequently coexist in the same patients or respond to the same treatments. Among the convenient truths of autoimmune and chronic inflammatory diseases, there is now agreement that these are complex conditions in which the individual genetic predisposition provides a rate of heritability. The concordance rates in monozygotic and dizygotic twins allows to estimate the weight of the environment in determining disease susceptibility, despite recent data supporting that only a minority of immune markers depend on hereditary factors. Concordance rates in monozygotic and dizygotic twins should be evaluated over an observation period to minimize the risk of false negatives and this is well represented by type I diabetes mellitus. Further, concordance rates in monozygotic twins should be compared to those in dizygotic twins, which share 50% of their genes, as in regular siblings, but also young-age environmental factors. Twin studies have been extensively performed in several autoimmune conditions and cumulatively suggest that some diseases, i.e. celiac disease and psoriasis, are highly genetically determined, while rheumatoid arthritis or systemic sclerosis have a limited role for genetics. These observations are necessary to interpret data gathered by genome-wide association studies of polymorphisms and DNA methylation in MZ twins. New high-throughput technological platforms are awaited to provide new insights into the mechanisms of disease discordance in twins beyond strong associations such as those with HLA alleles.

Shared genetic influences among childhood shyness, social competences, and cortical responses to emotions.

Visual event-related potentials (ERPs) evoked by facial expressions are useful to map socioemotional responses among shy children and to predict transition into social phobia. We investigated the sources of covariation among childhood shyness, social competences, and ERPs to other children's happy, neutral, and angry expressions. Electrophysiological and twin analyses examined the phenotypic and etiological association among an index of childhood shyness, an index of social competences, and ERP responses to facial expressions in 200 twins (mean age=9.23years). Multivariate twin analyses showed that the covariation among shyness, social competences, and a composite of a frontal late negative component occurring around 200-400ms in response to happy, neutral, and angry expressions could be entirely explained by shared genetic factors. A coherent causal structure links childhood shyness, social competences, and the cortical responses to facial emotions. A common genetic substrate can explain the interrelatedness of individual differences for childhood shyness, social competences, and some associated electrophysiological responses to socioemotional signals.

Normative data of the Magical Ideation Scale from childhood to adulthood in an Italian cohort.

The assessment of schizotypy allows to identify people at risk to develop psychosis. For this purpose, psychometric tools have been developed, such as the Magical Ideation Scale (MIS). This scale investigates attenuated forms of thought transmission experiences, thought withdrawal and aberrant beliefs, related to positive schizotypy. This study aims at providing an Italian version of the MIS and its normative data in the general population from childhood to adulthood, being the first study evaluating subjects under 17year-old. The Italian MIS version was translated by three independent operators and administered to 1378 non-clinical participants, stratified into four age groups (i.e., 8-13, 14-17, 18-24 and 25-34). The unidimensionality of the scale was supported, and its internal consistency was satisfactory (i.e., ordinal Cronbach's αs ranging from 0.86 to 0.90 in different age groups), as well as test-retest reliability (i.e., 1-month ICC of 0.82 in a retested sub-sample). Normative data for the age groups were provided. Specific gender and age-related differences in MIS score were found, i.e. females scored higher than males in the 25-34 age group, which in general, as a group, scored lower than all the other age groups. This study provided evidence of reliability for the Italian version of the MIS in childhood and adolescence, for the first time, as well as in adulthood, showing specific gender and age effects in the early adult cohort.

Circulating mitochondrial DNA increases with age and is a familiar trait: Implications for "inflamm-aging".

Mitochondrial components, including mitochondrial DNA (mtDNA), when released extracellularly, can act as "damage-associated molecular pattern" (DAMP) agents and cause inflammation. As many elderly people are characterized by a low-grade, chronic inflammatory status defined "inflamm-aging," we evaluated if circulating mtDNA can contribute to this phenomenon. Eight hundred and thirty-one Caucasian subjects were enrolled in the study, including 429 siblings aged 90-104 (90+ siblings). mtDNA plasma levels increased gradually after the fifth decade of life. In 90+ subjects, mtDNA values of two members of the same sibling relationship were directly correlated, suggesting a role for familiar/genetic background in controlling the levels of circulating mtDNA. The subjects with the highest mtDNA plasma levels had the highest amounts of TNF-α, IL-6, RANTES, and IL-1ra; the subjects with the lowest mtDNA levels had the lowest levels of the same cytokines. In vitro stimulation of monocytes with mtDNA concentrations similar to the highest levels observed in vivo resulted in an increased production of TNF-α, suggesting that mtDNA can modulate the production of proinflammatory cytokines. Our findings therefore show that circulating mtDNA increases with age, and can significantly contribute to the maintenance of the low-grade, chronic inflammation observed in elderly people.

Genetic and environmental influences underlying the relationship between autistic traits and temperament and character dimensions in adulthood.

BACKGROUND: In recent years, several twin studies adopted a dimensional approach to Autism Spectrum Disorders (ASD) and estimated the contribution of genetic and environmental influences to variation in autistic traits. However, no study was performed on adults over 18 years of age and all but two studies were based on parent or teacher ratings. Also, the genetic and environmental contributions to the interplay between autistic traits and adult personality dimensions have not been investigated. METHODS: A sample of 266 complete twin pairs (30% males, mean age 40 ± 12 years) drawn from the population-based Italian Twin Register was administered the Autism-Spectrum Quotient, Temperament and Character Inventory (TCI-125), and General Health Questionnaire (GHQ-12). Genetic structural equation modelling was performed with the Mx program. Estimates were adjusted for gender, age, and GHQ-12 score. RESULTS: Genetic factors accounted for 44% and 20%-49% of individual differences in autistic traits and TCI dimensions, respectively. Unshared environmental factors explained the remaining proportion of variance. Consistently with the notion of a personality profile in ASD characterised by obsessive temperament, autistic traits showed significant phenotypic correlations with several TCI dimensions (positive: HA; negative: NS, RD, SD, C). Genetic and unshared environmental correlations between AQ and these TCI dimensions were significant. The degree of genetic overlap was generally greater than the degree of environmental overlap. CONCLUSIONS: Despite some limitations, this study suggests that genetic factors contribute substantially to individual differences in autistic traits in adults, with unshared environmental influences also playing an important role. It also suggests that autistic traits and the majority of temperament and character dimensions share common genetic and environmental aetiological factors.

Modest genetic influence on bronchodilator response: a study in healthy twins.

AIM: To determine the reasons for large standard deviation of bronchodilator response (BDR) and establish whether there is a potential heritable component in healthy subjects. METHODS: 67 monozygotic and 42 dizygotic adult twin pairs were assessed for bronchodilator response (% change in FEV1 after inhaling 400 µg salbutamol). Univariate quantitative genetic modeling was performed. RESULTS: Multiple regression modeling showed a significant association between BDR and sex and baseline FEV1 (P<0.05), while no association was found with smoking habits, body mass index, or age. Within pair correlation in monozygotic twins was modest (0.332), but higher than in dizygotic twins (0.258). Age-, sex-, and baseline FEV1-adjusted genetic effect accounted for 14.9% (95% confidence interval, CI 0%-53.1%) of the variance of BDR, shared environmental effect for 18.4% (95% CI 0%-46.8%), and unshared environmental effect for 66.8% (95% CI 46.8%-88.7%). CONCLUSION: Our twin study showed that individual differences in BDR can be mostly explained by unshared environmental effects. In addition, it is the first study to show low, insignificant hereditary influences, independently from sex, age, and baseline FEV1.

[Determinants of eating behaviour: the contribution of twin studies]. / Determinanti del comportamento alimentare: il contributo degli studi sui gemelli.

This review includes relevant twin studies conducted on eating habits and preferences, and on endophenotypes of disordered eating behaviour in general population, non-clinical settings. The twin study design is presented, along with its assumptions and possible applications in aetiological and public health epidemiology. Subsequently, the strategy for the search of the scientific literature and the exclusion criteria are reported. Then, the analysis of the studies included in this review is performed, with a brief description of targeted outcomes, twin model used, sample characteristics and findings. Finally, key messages emerging from the review are highlighted, emphasizing their value for bridging the current gaps in the understanding of determinants of eating behaviour and their mode of action.

Genetic influence on capillary oxygen saturation: a twin study.

BACKGROUND: While heritability has been shown for daytime sleepiness, the heritability of daytime capillary oxygen saturation (SpO(2)) has not been described in detail. Our aim was to estimate the role of genes and environmental factors--both shared and unshared--in the variation of daytime SpO(2). METHODS: A total of 193 adult healthy twin pairs (138 monozygotic, 55 dizygotic) were recruited in Hungary and in the United States [age = 43.6 ± 15.6 years (mean ± SD)]. SpO(2) was measured by pulse oximetry. Univariate quantitative genetic modeling was performed to decompose the phenotypic variance of the considered parameter into heritability (A), shared (C), and unshared (E) environmental effects. RESULTS: SpO(2) twin correlation in monozygotic twins was stronger than in dizygotic twins (0.30 and -0.15, respectively, p < 0.05). Age-, sex-, country-, and body mass index-adjusted genetic effects accounted for 26 % (95 % CI 10, 45 %) of the variance of SpO(2), and the unshared environmental component explained the remaining 74 % (95 % CI 59, 89 %). No shared environmental influence on SpO(2) was detected. The heritability of SpO(2) was not different between smokers and nonsmokers. CONCLUSION: In summary, individual differences in daytime SpO(2) are explained by genetic and unshared environmental effects. The strong unshared environmental influence highlights the role of prevention of known environmental risk factors.

Piccolipiù, a multicenter birth cohort in Italy: protocol of the study.

BACKGROUND: The fetal and infant life are periods of rapid development, characterized by high susceptibility to exposures. Birth cohorts provide unique opportunities to study early-life exposures in association with child development and health, as well as, with longer follow-up, the early life origin of adult diseases. Piccolipiù is an Italian birth cohort recently set up to investigate the effects of environmental exposures, parental conditions and social factors acting during pre-natal and early post-natal life on infant and child health and development. We describe here its main characteristics. METHODS/DESIGN: Piccolipiù is a prospective cohort of expected 3000 newborns, who will be recruiting in six maternity units of five Italian cities (Florence, Rome, Trieste, Turin and Viareggio) since October 2011. Mothers are contacted during pregnancy or at delivery and are offered to participate in the study. Upon acceptance, their newborns are recruited at birth and followed up until at least 18 years of age. At recruitment, the mothers donate a blood sample and complete a baseline questionnaire. Umbilical cord blood, pieces of umbilical cord and heel blood spots are also collected. Postnatal follow-up currently occurs at 6, 12, and 24 months of age using on-line or postal self administered questionnaire; further questionnaires and medical examinations are envisaged. Questionnaires collect information on several factors, including mother's and/or child's environmental exposures, anthropometric measures, reproductive factors, diet, supplements, medical history, cognitive development, mental health and socioeconomic factors. Health promotion materials are also offered to parents. DISCUSSION: Piccolipiù will broaden our understanding of the contribution of early-life factors to infant and child health and development. Several hypotheses on the developmental origins of health can be tested or piloted using the data collected from the Piccolipiù cohort. By pooling these data with those collected by other existing birth cohorts it will be possible to validate previous findings and to study rare exposures and outcomes.