Breastfeeding is considered the best and most natural way of feeding infants during the first months of life. Breastfeeding has multiple short- and long-term benefits for the health of the mother and babies, and from an evolutionist standpoint, it would be a behavior worth preserving throughout time. The aim of the present study was to explore the relative influence of genetic and environmental factors in this behavior. Three hundred and ninety pairs of adult female twins provided information about whether they breastfed their children and for how long. Three variables were analyzed: initiation and duration for the first baby, and mean duration for the complete offspring. Polychoric correlations were consistently higher for monozygotic twins, supporting a role for genetic factors (0.49 vs. 0.22 for initiation; 0.44 vs. 0.22 for duration in the first newborn; and 0.52 vs. 0.31 for duration on average). Model-fitting analyses found that in the best-fitting model, variance was explained by additive genetic and non-shared environmental factors, with estimated heritabilities ranging from 0.39 to 0.52 in the measures studied. The rest of the variance would be due to unique environmental factors. We conclude that genetic factors have a significant impact on the complex behavior of breastfeeding.

Pregnancy- and birth-related factors may have an effect on handedness. Compared with singletons, twins have a lower birth weight, shorter gestational age, and are at higher risk for birth complications. We tested whether the prevalence of left-handedness is higher among twins than singletons, and if so, whether that difference is fully explained by pregnancy and birth-related differences between twins and singletons. We analyzed Finnish population-based datasets; included were 8,786 twins and 5,892 singletons with information on birth weight (n = 12,381), Apgar scores (n = 11,129), and gestational age (n = 11,811). Two twin cohorts were involved: FinnTwin12 included twins born during 1983–1987, and FinnTwin16 included twins born during 1974–1979. We had two comparison groups of singletons: 4,101 individuals born during 1986–1988 and enrolled in the Helsinki Ultrasound Trial, and 1,791 individuals who were partners of FinnTwin16 twins. We used logistic regression models with writing hand as the outcome for comparison and evaluating effects of covariates. Left-handedness was more common in twins (9.67%) than in singletons (8.27%; p = .004). However, Apgar scores were associated with handedness, and after controlling for covariates, we found no difference in the prevalence of left-handedness between twins and singletons. Increased left-handedness among twins, often reported by others, was evident in our data, but only among our older twin cohorts, and that association disappeared after removing effects of perinatal covariates.

Telomere length is widely considered as a marker of biological aging. Clinical studies have reported associations between reduced telomere length and hypertension. The aim of this study was to compare telomere length in hypertensive and normotensive mice at pre-disease and established disease time points to determine whether telomere length differs between the strains before and after the onset of disease. Genomic DNA was extracted from kidney and heart tissues of 4-, 12-, and 20-week-old male hypertensive (BPH/2J) and normotensive (BPN/3J) mice. Relative telomere length (T/S) was measured using quantitative PCR. Age was inversely correlated with telomere length in both strains. In 4-week-old pre-hypertensive animals, no difference in T/S was observed between BPH/2J and BPN/3J animals in kidney or heart tissue (kidney p = 0.14, heart p = 0.06). Once the animals had established disease, at 12 and 20 weeks, BPH/2J mice had significantly shorter telomeres when compared to their age-matched controls in both kidney (12 weeks p < 0.001 and 20 weeks p = 0.004) and heart tissues (12 weeks p < 0.001 and 20 weeks p < 0.001). This is the first study to show that differences in telomere lengths between BPH/2J and BPN/3J mice occur after the development of hypertension and do not cause hypertension in the BPH/2J mice.

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

Nearly all twin registers are based in developed countries and there is no twin register in the developing world. Our objectives were to initiate the process of establishing a nationwide twin register in Sri Lanka by starting a volunteer register first and working towards a population-based register. Regular newspaper advertisements, feature articles, radio talks, and television programmes were used to publicise a competition for twins, their parents/relatives and friends requesting them to participate by sending in details of twins. The competition ran from 28 March 1997 for a period of 3 months. It offered prizes for three winners selected by drawing lots. Advertisements highlighted the objective of the competition as establishing a twin register for future research and emphasised that informed consent would be obtained for individual research projects. Those who registered comprise 4602 twin pairs (same sex: male – 1564, female – 1885; different sex – 1153), 80 sets of triplets (same sex: male – 17, female – 31; different sex – 42) and two sets of quadruplets (different sex). The oldest twins, triplets, quadruplets are 85, 46, and 5 years old, respectively; 88.0% of twins are less than 30 years old. Although others have previously used media publicity to enrol twins in twin registers, we believe this to be the first time that twins have been enrolled through competition. We have more young twins, and our gender and zygosity proportions after applying Weinburg's rule do not match the proportions expected from a volunteer twin sample. Establishing a twin register for research purposes has proved possible in a developing country. Twin Research (2000) 3, 202–204.

The importance of including developmental and environmental measures in genetic studies of human pathology is widely acknowledged, but few empirical studies have been published. Barriers include the need for longitudinal studies that cover relevant developmental stages and for samples large enough to deal with the challenge of testing gene–environment–development interaction. A solution to some of these problems is to bring together existing data sets that have the necessary characteristics. As part of the National Institute on Drug Abuse-funded Gene-Environment-Development Initiative, our goal is to identify exactly which genes, which environments, and which developmental transitions together predict the development of drug use and misuse. Four data sets were used of which common characteristics include (1) general population samples, including males and females; (2) repeated measures across adolescence and young adulthood; (3) assessment of nicotine, alcohol, and cannabis use and addiction; (4) measures of family and environmental risk; and (5) consent for genotyping DNA from blood or saliva. After quality controls, 2,962 individuals provided over 15,000 total observations. In the first gene–environment analyses, of alcohol misuse and stressful life events, some significant gene–environment and gene–development effects were identified. We conclude that in some circumstances, already collected data sets can be combined for gene–environment and gene–development analyses. This greatly reduces the cost and time needed for this type of research. However, care must be taken to ensure careful matching across studies and variables.

The objective of this study was to evaluate the impact of one abnormal fetus in a twin pregnancy, to compare impact of chorionicity and clinical outcome of intervention and expectant management. Thirty-seven dichorionic (DC) twins and 18 monochorionic (MC) twins complicated with one malformed fetus were evaluated for gestational age, birthweight and perinatal outcome. Six hundred and forty-two twin pregnancies were evaluated in the database. The control groups consisted of 429 DC and 86 MC twins without anomalous fetus. Mean birthweight and gestational age at birth for DC control group were (n = 429; 2137g and 34.71 weeks), DC study group, n = 37; 2117g (p = .338) and 33.97 weeks (p = .311), and DC study group with major malformations, n = 30; 2019g (p = .289) and 33.3 weeks (p = .01), and showed only significance for gestational age. There was no statistical significance between MC control group, n = 86; 2097g and 34.93 weeks, and MC study group, n = 18; 2237g (p = .338), and 34.42 weeks (p = .502). Because of limited data, the preliminary evaluation for expectant management and intervention, and survival of at least one normal fetus showed no impact. We conclude that, although, all DC twin pregnancies have a risk for preterm delivery, DC twins complicated with major malformation of one twin, have a lower mean gestational age at birth. Preliminary results for intervention does not improve fetal outcome for DC and MC twins and needs further evaluation with greater studies of impact or review.

Twin registries often take part in large collaborative projects and are major contributors to genome-wide association (GWA) meta-analysis studies. In this article, we describe genotyping of twin-family populations from Australia, the Midwestern USA (Avera Twin Register), the Netherlands (Netherlands Twin Register), as well as a sample of mothers of twins from Nigeria to assess the extent, if any, of genetic differences between them. Genotyping in all cohorts was done using a custom-designed Illumina Global Screening Array (GSA), optimized to improve imputation quality for population-specific GWA studies. We investigated the degree of genetic similarity between the populations using several measures of population variation with genotype data generated from the GSA. Visualization of principal component analysis (PCA) revealed that the Australian, Dutch and Midwestern American populations exhibit negligible interpopulation stratification when compared to each other, to a reference European population and to globally distant populations. Estimations of fixation indices (FST values) between the Australian, Midwestern American and Netherlands populations suggest minimal genetic differentiation compared to the estimates between each population and a genetically distinct cohort (i.e., samples from Nigeria genotyped on GSA). Thus, results from this study demonstrate that genotype data from the Australian, Dutch and Midwestern American twin-family populations can be reasonably combined for joint-genetic analysis.

The association of VEGF+405G/C (where VEGF is vascular endothelial growth factor) polymorphism and malignancy susceptibility attracts considerable attention because VEGF is one of the most potent angiogenic factors and plays a critical role in the onset and development of malignancy. However, the published findings remain inconclusive. In order to derive a more precise assessment of the association, we performed a meta-analysis including 30 published case-control studies from PubMed, Embase, and Ovid databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. In the pooled analyses, no significant association was found between VEGF+405G/C polymorphism and malignancy susceptibility in different genetic models (G-allele vs. C-allele: OR = 1.00, 95% CI: 0.93–1.07; CC vs. GG: OR = 1.01, 95% CI: 0.88–1.15; GC+CC vs. GG: OR = 1.00, 95% CI: 0.91–1.10; CC vs. GC+GG: OR = 1.01, 95% CI: 0.90–1.13). When stratified by ethnicity, a weak association between this polymorphism and malignancy susceptibility was found in African under allelic frequency comparison (OR = 0.65, 95% CI: 0.43–0.98) and dominant genetic model comparison (OR = 1.95, 95% CI: 1.09–3.50). In summary, although our meta-analysis indicated a weak association of VEGF+405G/C polymorphism with malignancy susceptibility in African, no persuasive evidence of association between the polymorphism and malignancy susceptibility was detected in the pooled analyses. Therefore, more studies with larger scale of participants, especially Africans, are required to further evaluate gene-environment interaction on this polymorphism and malignancy susceptibility.

The study investigated the clinical and pathomorpho- logical characteristics of monochorionic diamniotic twin gestations complicated by the spontaneous loss of one fetus during the first trimester. Nine monochorionic diamniotic twin gestations were analyzed in which the demise of one fetus occurred during the first trimester. During the course of the study, 178 twin gestations were sonographically identified during the first trimester. Forty-three (24.2%) were complicated by the intrauterine demise of one fetus before the end of the 12th week of pregnancy. Nine cases were monochorionic diamniotic. The gestational age of the demised fetuses ranged between 5 and 11 weeks (mean 7.4 weeks). The prognoses for the surviving fetuses were rather poor with the surviving co-twin dying 1 to 3 weeks after the first twin, with abortion of both fetuses. In only one case was gestation concluded on the 40th week with delivery of a live neonate. No blood coagulation changes were observed in the affected pregnant women, and the one live newborn did not reveal any haematological or neurological abnormalities. A postnatal study provided evidence for the history of monochorionic diamniotic placentation in all of the cases. In two cases, probable causes of fetal death were established (congenital malformation, the presence of anastomoses between blood vessels). The obtained results suggest an extremely high risk of mortality for the surviving twin fetus following the co-twin's death in cases of monochorial placentation. The morphological evaluation of placentas and fetal membranes enables the establishment of the type of placenta and, in certain cases, the probable cause of the intrauterine demise of one twin fetus during the first trimester of monochorionic diamniotic twin gestation.

The objective of this study was to evaluate associations between adverse outcomes in twin pregnancies and preterm prelabour rupture of membranes (PPROM). A chart review of 246 consecutive twin pregnancies with confirmed PPROM was conducted. Regression analysis (β [natural log of the odds ratio] and odds ratio [OR]) was performed to identify independent predictors. Two hundred and forty-six twin pregnancies, 492 liveborns, and 20 neonatal deaths. Mean (SD) PPROM gestational age (GA): 31.3 (3.8) wk; delivery GA: 32.0 (3.3) wk. PPROM < 30wk was associated with increased parity (OR: 2.66), and log (admission leukocyte count) (OR: 9.99). Shortened latency was associated with PPROM GA (β = −0.17) and chorioamnionitis (β = 0.95). Neonatal sepsis was predicted by lower delivery GA (OR: 2.04). Adverse perinatal outcomes were protected against by older GA at PPROM (OR 0.53) and shortened latency (OR 0.73). It was concluded that increased leukocytosis and parity implies an infectious aetiology in earlier PPROM. Increased risk for neonatal sepsis at earlier delivery GA is consistent with gestation-dependent fetal immunocompetence. Early PPROM and long latencies were associated with increased adverse perinatal outcomes.

The Twin Research Registry (TRR) at SRI International is a community-based registry of twins established in 1995 by advertising in local media, mainly on radio stations and in newspapers. As of August 2012, there are 3,120 same- and opposite-sex twins enrolled; 86% are 18 years of age or older (mean age 44.9 years, SD 16.9 years) and 14% less than 18 years of age (mean age 8.9 years, SD 4.5); 67% are female, and 62% are self-reported monozygotic (MZ). More than 1,375 twins have participated in studies over the last 15 years in collaboration with the University of California Medical Center in San Francisco, the University of Texas MD Anderson Cancer Center, and the Stanford University School of Medicine. Each twin completes a registration form with basic demographic information either online at the TRR Web site or during a telephone interview. Contact is maintained with members by means of annual newsletters and birthday cards. The managers of the TRR protect the confidentiality of twin data with established policies; no information is given to other researchers without prior permission from the twins; and all methods and procedures are reviewed by an Institutional Review Board. Phenotypes studied thus far include those related to nicotine metabolism, mutagen sensitivity, pain response before and after administration of an opioid, and a variety of immunological responses to environmental exposures, including second-hand smoke and vaccination for seasonal influenza virus and Varicella zoster virus. Twins in the TRR have participated in studies of complex, clinically relevant phenotypes that would not be feasible to measure in larger samples.

A lifetime history of alcohol dependence has been associated with elevations in neuroticism in Mexican American young adults. The identification of genetic markers associated with neuroticism and their influence on the development of alcohol use disorders (AUD) may contribute to our understanding of the relationship between personality traits and the increased risk of AUD in Mexican Americans. The purpose of this study was to investigate associations between neuroticism and 13 single nucleotide polymorphisms (SNPs) in the nicotinic acetylcholine (nAChR) α5-subunit (CHRNA5) and α3-subunit (CHRNA3) genes in young adult Mexican American men and women. Participants were 465 young adult Mexican American men and women who are literate in English and are residing legally in San Diego County. Each participant gave a blood sample and completed a structured diagnostic interview. Neuroticism was assessed using the Maudsley Personality Inventory. The minor alleles of four CHRNA5 polymorphisms (rs588765, rs601079, rs680244 and rs555018) and three CHRNA3 polymorphisms (rs578776, rs6495307 and rs3743078) showed associations with neuroticism. Several of these SNPs also displayed nominal associations with DSM-IV alcohol and nicotine dependence, but tests of mediation suggested that these relations could be partially explained by the presence of co-occurring neuroticism. These findings suggest that genetic variations in nicotinic receptor genes may influence the development of neuroticism, which in turn is involved in the development of AUDs and nicotine dependence in Mexican American young adults.

Neuroimaging studies have indicated abnormalities in cortico-striato-thalamo-cortical circuits in obsessive–compulsive disorder patients, but results have not been consistent. Since there are significant sex differences in human brain anatomy and obsessive–compulsive symptomatology and its developmental trajectories tend to be distinct in males and females, we investigated whether sex is a potential source of heterogeneity in neuroimaging studies on obsessive–compulsive symptoms. We selected male and female twin pairs who were concordant for scoring either high or low for obsessive–compulsive symptoms and a group of discordant pairs where one twin scored high and the co-twin scored low. The design included 24 opposite-sex twin pairs. Magnetic resonance imaging scans of 31 males scoring high for obsessive–compulsive symptoms, 41 low-scoring males, 58 high-scoring females, and 73 low-scoring females were analyzed and the interaction of obsessive–compulsive symptoms by sex on gray matter volume was assessed using voxel-based morphometry. An obsessive–compulsive symptom by sex interaction was observed for the left middle temporal gyrus, the right middle temporal gyrus, and the right precuneus. These interactions acted to reduce or hide a main effect in our study and illustrate the importance of taking sex into account when investigating the neurobiology of obsessive–compulsive symptoms.

We report on a 3-year-old girl, from a 3-generation family with an FGFR3 Pro250Arg mutation, who in addition to craniosynostosis, had a laterality disorder and hepatoblastoma, following a pregnancy complicated by maternal insulin-dependent diabetes. The clinical features possibly result from the combined effects of the maternal diabetes and the familial FGFR3 mutation, thus representing a unique gene–environment interaction that may have implications for the understanding of the phenotypes described in this child.

Acephalus acardia is among the most severe malformations described in fetuses, with an incidence of about 1 in 35,000 births and is due to twin-to-twin transfusion syndrome, frequently occurring in monochorionic twin pregnancies. The severity of the syndrome depends upon the type of the anastomoses arising between the vascular networks of the two fetuses, usually configuring the ‘twin reverse arterial perfusion syndrome’. No clear and univocal etiological explanation is known, though few cases with chromosomal abnormalities have been reported so far. In some cases the fusion of two or more separate placentae of dizygotic fetuses occurs, leading to monochorionic twinning. Few cases of acardius amorphous with complete autoptical examination have been described so far. We report a case of acephalus acardius amorphus fetus, showing features of extremely severe sistemic immaturity with very few structured organs. Defined external and autoptic examinations have been performed on the dismorphic twin, along with the histological examination of tissue samples. Kariotype analysis showed sex discrepancy between the twins, as a normal female kariotype had been detected in the acephalus acardius while the living co-twin was a normal healthy male. The analysis of the placenta showed the vascular anomalies leading to the twin-to-twin transfusion syndrome.

Objective: Laser ablation of all placental vascular anastomoses is the optimal treatment for twin–twin transfusion syndrome (TTTS). However, two important controversies are apparent in the literature: (a) a gap between concept and performance, and (b) controversy regarding whether all the anastomoses can be identified endoscopically and whether blind lasering of healthy placenta is justified. The purpose of this article is: (a) to address the potential source of the gap between concept and performance by analyzing the fundamental steps needed to successfully accomplish the surgery, and (b) to discuss the resulting competency benchmarks reported with the different surgical techniques. Materials and Methods: Laser surgery for TTTS can be broken down into two fundamental steps: (1) endoscopic identification of the placental vascular anastomoses, (2) laser ablation of the anastomoses. The two steps are not synonymous: (a) regarding the endoscopic identification of the anastomoses, the non-selective technique is based upon lasering all vessels crossing the dividing membrane, whether anastomotic or not. The selective technique identifies and lasers only placental vascular anastomoses. The Solomon technique is based on the theory that not all anastomoses are endoscopically visible and thus involves lasering healthy areas of the placenta between lasered anastomoses, (b) regarding the actual laser ablation of the anastomoses, successful completion of the surgery (i.e., lasering all the anastomoses) can be measured by the rate of persistent or reverse TTTS (PRTTTS) and how often a selective technique can be achieved. Articles representing the different techniques are discussed. Results: The non-selective technique is associated with the lowest double survival rate (35%), compared with 60–75% of the Solomon or the Quintero selective techniques. The Solomon technique is associated with a 20% rate of residual patent placental vascular anastomoses, compared to 3.5–5% for the selective technique (p < .05). Both the Solomon and the selective technique are associated with a 1% risk of PRTTTS. Adequate placental assessment is highest with the selective technique (99%) compared with the Solomon (80%) or the ‘standard’ (60%) techniques (p < .05). A surgical performance index is proposed. Conclusion: The Quintero selective technique was associated with the highest rate of successful ablation and lowest rate of PRTTTS. The Solomon technique represents a historical backward movement in the identification of placental vascular anastomoses and is associated with higher rate of residual patent vascular communications. The reported outcomes of the Quintero selective technique do not lend support to the existence of invisible anastomoses or justify lasering healthy placental tissue.

Twin–twin transfusion syndrome (TTTS) is a severe complication of twin pregnancies with high risk for perinatal mortality and long-term morbidity. This cross-sectional cohort study aimed to determine parenting stress and psychosocial health in mothers with a pregnancy complicated by TTTS that had been managed with laser ablation of communicating placental vessels. Questionnaires were sent to the mothers for completion: Parenting Stress Index (PSI), Edinburgh Postnatal Depression Scale (EPDS) and a semi-structured questionnaire related to mental health problems and support received from health professionals. Thirty-seven mothers were sent questionnaires with 32 being returned. The results showed that 47% of women had total scores equal to or greater than the 85th percentile on the PSI, which is considered abnormally high. Twenty-six per cent of mothers had evidence of depression on the EPDS. Mothers of children with prolonged medical conditions or neurological problems had significantly higher scores (p =.011). Parenting stress was not associated with high scores on the EPDS. Medical and midwifery staff were considered to provide high levels of support, with social work providing none or low levels of support. In conclusion, women whose TTTS pregnancy was managed by laser surgery have high levels of parenting stress. As the results showed that parenting stress cannot be predicted at the time of hospitalization, it is suggested that more support should be provided in hospital with further follow-up after discharge.

Genomics tools (gene- and protein-expression studies) can be used to find possible target genes involved in a quantifiable trait or disease state. However in many instances, cells and tissues directly involved in the trait's expression, for example, brain tissue, are not amenable for gene expression analysis. Whole blood cells share a molecular make-up for cellular communication and gene regulation systems with many other cell types, for example, neuronal cells, and have the advantage of being very accessible for gene profiling. We investigated the feasibility of nationwide blood sample collection for lymphocyte RNA isolation and real-time PCR analysis to quantify genomic responses. We tested several designs for blood collection and storage: blood sampling in PAXgene blood collection tubes and storage at −20°C, blood sampling in heparin tubes and decanting the samples (with or without in-vitro stimulus) into either PAXgene blood collection tubes and storage at −20°C, or polypropylene tubes followed by snap-freezing and storage at −80°C. The latter procedure is the best cost-wise when only small amounts of total RNA are needed for downstream applications. Lymphocyte gene expression studies are most likely hampered by the quality of isolated RNA rather than the sampling method. We show that large-scale nationwide sample collections did not alter RNA quality or gene expression levels when compared to sampling and processing in a more controlled way. To this end, we present an optimized protocol for easy and standardized isolation of high quality RNA using the PAXgene isolation kit. Based on these results, we suggest that whole blood genomic data can be used as a genomic probe in experimental and clinical research.

The aim of this study was to determine whether identity-by-descent (IBD) information for affected sib pairs (ASPs) can be used to select a sample of cases for a genetic case-control study which will provide more power for detecting association with loci in a known linkage region. By modeling the expected frequency of the disease allele in ASPs showing IBD sharing of 0, 1, or 2 alleles, and considering additive, recessive, and dominant disease models, we show that cases selected from IBD 2 families are best for this purpose, followed by those selected from IBD 1 families; least useful are cases selected from IBD 0 families.