Genome-wide association studies (GWAS) of attention-deficit/hyperactivity disorder (ADHD) offer the benefit of a hypothesis-free approach to measuring the quantitative effect of genetic variants on affection status. Generally the findings of GWAS relying on ADHD status have been non-significant, but the one study using quantitative measures of symptoms found SLC9A9 and SLC6A1 were associated with inattention and hyperactivity–impulsivity. Accordingly, we performed a GWAS using quantitative measures of each ADHD subtype measured with the Strengths and Weaknesses of ADHD and Normal Behaviour (SWAN) scale in two community-based samples. This scale captures the full range of attention and kinetic behavior; from high levels of attention and appropriate activity to the inattention and hyperactivity–impulsivity associated with ADHD within two community-based samples. Our discovery sample comprised 1,851 participants (mean age = 22.8 years [4.8]; 50.6% female), while our replication sample comprised 155 participants (mean age = 26.3 years [3.1]; 68.4% females). Age, sex, age × sex, and age2 were included as covariates and the results from each sample were combined using meta-analysis, then analyzed with a gene-based test to estimate the combined effect of markers within genes. We compare our results with markers that have previously been found to have a strong association with ADHD symptoms. Neither the GWAS nor subsequent meta-analyses yielded genome-wide significant results; the strongest effect was observed at rs2110267 (4.62 × 10−7) for symptoms of hyperactivity–impulsivity. The strongest effect in the gene-based test was for GPR139 on symptoms of inattention (6.40 × 10−5). Replication of this study with larger samples will add to our understanding of the genetic etiology of ADHD.

Children born with non-optimal birth characteristics — that is, are small for gestational age and/or preterm — have an increased risk for several long-term effects such as neurological sequelae and chronic disease. The purpose of this study was to examine whether twins exhibited a different outcome, compared with singletons, in terms of hospitalization during adolescence and early adulthood, and to what extent differences remain when considering the divergence in birth characteristics between singletons and twins. Persons born between 1973 and 1983 in Sweden and surviving until age 13 were included and followed until the end of 2006. Data on birth characteristics, parental socio-demographic factors, and hospitalizations were collected from national registers. Adjusting for parental socio-demographic factors, twins had a higher risk of being hospitalized than singletons (odds ratio, OR = 1.17, 95% confidence interval, CI = 1.10–1.25) and more often due to ‘Congenital anomalies’ (OR = 1.18, 95% CI = 1.06–1.28), ‘Infections’ (OR = 1.14; 95% CI = 1.08–1.20), ‘External causes of illness’ (OR = 1.10, 95% CI = 1.06–1.15), and ‘Diseases of the nervous system’ (OR = 1.18, 95% CI = 1.10–1.26). Stratifying for birth characteristics, this difference diminishes, and for some diagnoses non-optimal twins seem to do slightly better than non-optimal singletons. Thus, twins with non-optimal birth characteristics had a lower risk of hospitalization than non-optimal singletons on, for example, ‘Congenital anomalies’ and ‘Diseases of the nervous system’ (OR = 0.86, 95% CI = 0.77–0.96; OR = 0.88, 95% CI = 0.81–0.97, respectively) and Total (any) hospitalization (OR = 0.87, 95% CI = 0.83–0.92). Among those with optimal birth characteristics, twins had an increased hospitalization due to ‘External causes of illness’ (OR = 1.07, 95% CI = 1.02–1.13) compared with optimal singletons. Twins have higher hospitalization rates than singletons. In stratifying for birth characteristics, this difference diminishes, and for some diagnoses, non-optimal twins seem to do less poorly than non-optimal singletons.

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.

The French mathematician Bertillon reasoned that the number of dizygotic (DZ) pairs would equal twice the number of twin pairs of unlike sexes. The remaining twin pairs in a sample would presumably be monozygotic (MZ). Weinberg restated this idea and the calculation has come to be known as Weinberg's differential rule (WDR). The keystone of WDR is that DZ twin pairs should be equally likely to be of the same or the opposite sex. Although the probability of a male birth is greater than .5, the reliability of WDR's assumptions has never been conclusively verified or rejected. Let the probability for an opposite-sex (OS) twin maternity be pO, for a same-sex (SS) twin maternity pS and, consequently, the probability for other maternities 1 − pS − pO. The parameter estimates $\hat p_O$ and $\hat p_S$ are relative frequencies. Applying WDR, the MZ rate is m = pS − pO and the DZ rate is d = 2pO, but the estimates $\hat m$ and $\hat d$ are not relative frequencies. The maximum likelihood estimators $\hat p_S$ and $\hat p_O$ are unbiased, efficient, and asymptotically normal. The linear transformations $\hat m = \hat p_S - \hat p_O$ and ${\skew6\hat d} = 2\hat p_O$ are efficient and asymptotically normal. If WDR holds they are also unbiased. For the tests of a set of m and d rates, contingency tables cannot be used. Alternative tests are presented and the models are applied on published data.

The Quebec Newborn Twin Study (QNTS) is an ongoing prospective longitudinal follow-up of a birth cohort of twins born between 1995 and 1998 in the greater Montreal area, Québec, Canada. The goal of QNTS is to document individual differences in the cognitive, behavioral, and social-emotional aspects of developmental health across childhood, their early bio-social determinants, as well as their putative role in later social-emotional adjustment, school and health outcomes. A total of 662 families of twins were initially assessed when the twins were aged 6 months. These twins and their family were then followed regularly. QNTS has 14 waves of data collected or planned, including 5 in preschool. Over the past 15 years, a broad range of physiological, cognitive, behavioral, school, and health phenotypes were documented longitudinally through multi-informant and multi-method measurements. QNTS also entails extended and detailed multi-level assessments of proximal (e.g., parenting behaviors, peer relationships) and distal (e.g., family income) features of the child's environment. This detailed longitudinal information makes QNTS uniquely suited for the study of the role of the early years and gene-environment transactions in development.

The aim of this study was to assess the aorta–intima thickness (aIT) and serum metabolomic profile in selective intrauterine growth-restricted (sIUGR) monochorionic diamniotic (MCDA) twin fetuses presenting Doppler velocimetry alterations. Fetal abdominal aIT was measured by ultrasound at 32 weeks of gestation, enrolling 24 MCDA twin fetuses (8 sIUGR and 16 controls). sIUGR twin fetuses were classified into two groups: Group 1 consisted of sIUGR with abnormal umbilical artery (UA) Doppler waveforms and Group 2 included sIUGR with normal UA Doppler. Group 3 were control fetuses appropriate for gestational age (AGA). Fetal blood samples were obtained from the umbilical vein immediately after fetal extraction. A non-targeted metabolomic profiling investigated fetal metabolism alterations by using liquid chromatography–high-resolution mass spectrometry (LC-HRMS). Median fetal aIT was significantly larger in Group 1 (median value = 0.9 mm; range = 0.8–1.0 mm; p < .002) and Group 2 (median value = 0.8 mm; range = 0.7–0.8 mm; p < .002) than in AGA Group 3 (median value = 0.5 mm; range = 0.4–0.6 mm; p < .002). Metabolomic analyses, performed on four sIUGR cases (Group 1) compared with four AGA co-twins, showed an upregulation of phenylalanine, sphingosine, glycerophosphocholine, and choline, and a downregulation of valine, tryptophan, isoleucine, and proline sIUGR Group 1 compared with AGA. Although for metabolomics data only a statistical tendency (and not a statistical significance) was reached due to the small sample size, we believe that our results represent a valid starting point for further in-depth metabolomic and proteomic investigations of sIUGR in MCDA fetuses.

Twin–twin transfusion syndrome (TTTS) is an antenatal complication of monochorionic multiple gestations. There have been few studies exploring the role of laser photocoagulation or outcomes following treatment in monochorionic triplet pregnancies with TTTS. We present a case where TTTS and twin anemia–polycythemia sequence (TAPS) complicated a monochorionic triplet pregnancy. Following the laser photocoagulation to treat the TTTS between the triplets, an intra-uterine death occurred in one triplet and TAPS developed in the remaining two triplets. Intervention in this case resulted in a 2-week prolongation of pregnancy and a positive outcome for the remaining fetuses. This case and other published data reviewed in this article suggest that laser photocoagulation has a potential role for TTTS in monochorionic triplet pregnancies.

Objective: To assess the association of mode of conception and sex concordance with neonatal outcomes in very preterm twins. Study design: Twin pairs born at gestational age ≤32 weeks and admitted to a Level 3 neonatal intensive care unit (NICU) in 2010–2011 were retrospectively identified from the Canadian Neonatal Network™ database. A composite outcome representing neonatal mortality or any severe morbidity (intraventricular hemorrhage grades ≥3 or periventricular leukomalacia, retinopathy of prematurity stages ≥3, bronchopulmonary dysplasia, or necrotizing enterocolitis stages ≥2) was compared between twins conceived using assisted reproduction technologies (ARTs) or spontaneously (SP), and tested for association with sex concordance in individual-level and pair-wise multivariable logistic regression analyses. Results: Study subjects included 1,508 twins from 216 ART (53 [25%] male–male, 104 [48%] male–female, and 59 [27%] female–female) and 538 SP (192 [36%] male–male, 123 [23%] male–female, and 223 [41%] female–female) pairs. No statistically significant association was detected between mode of conception and the composite outcome of mortality/morbidities. The composite outcome was significantly higher in same-sex than in opposite-sex twins (OR = 1.68; 95% CI = [1.09, 2.59]). This relationship was most pronounced in ART pairs (OR = 2.25; 95% CI = [1.02, 4.98]), with increased rates in one or both twins from male–male versus opposite-sex ART pairs (OR = 3.0; 95% CI = [1.07, 8.36]). Conclusion: Same-sex pairing was associated with higher mortality/morbidities in very preterm twins admitted to the NICU, and can be used in clinical practice to identify twins at higher risk of adverse neonatal outcomes.

There is a long-held credo, as illustrated in Langman's Medical Embryology (11th ed., Sadler, 2010), that dichorionic diamniotic (DD) twins develop after embryo splitting in the early stages of embryonic development. However, from our clinical experiences of the examination of data from single-embryo transfers in 16 fertility clinics in Japan and from various reports, the majority of occurrences of DD twins have been found in the blastocyst stages.

Cataract, defined as opacity of the lens in one or both eyes, is a major cause of blindness throughout the world, and not uncommon, particularly in the elderly population. However, congenital cataracts are rare and occur with a frequency of 30 cases in 100,000 births. About one-third of the cases fall into the group inherited without systemic abnormality. Importantly, congenital cataracts produce deprivation amblyopia, refractive amblyopia, and retinal detachment, leading to lifelong visual impairment. Successful management is dependent on early diagnosis and referral for surgery when indicated. Here we present a case of hereditary bilateral cataracts in a dizygotic twin detected on prenatal ultrasound examinations and postnatally confirmed as congenital cataracts associated with posterior lenticonus.

The associations between height and reproductive success in humans have attracted long-time scientific interest, but in addition to rather mixed previous results, little is still known about the background mechanisms of these associations. We analyzed the association of adult height with age at first birth and lifetime reproductive success using a twin study design that is able to optimally take into account family background and estimate the contributions of genetic and environmental factors. Information on live births as of June 2009 for 7,830 Finnish twins born 1950–1957 was extracted from the national population register. We found evidence for non-linear associations in men, as men in the third sex-specific height quintile had the highest probability of having one to two children, or three or more children at individual level analyses, and also to have any children when analyzing twin pairs discordant for height. Furthermore, the probability of having a spouse was highest in the third height category in men. Short stature was associated with earlier age at first birth in females, explained by correlated genetic factors, but not with lifetime number of children or having a spouse. Our results suggest that average stature may give some advantage for reproduction in males. In females, genetic factors explained the association between short stature and young age at first birth, which may suggest the role of hormonal factors.

Non-syndromic agenesis of permanent teeth is one of the most common anomalies in human development, a multifactorial characteristic caused by genetic and environmental factors. We describe a pair of monozygotic twins who showed second premolar and third molar agenesis, albeit with different expressions. We studied the DNA of two genes, paired domain box gene 9 (PAX9) and muscle segment homeodomain-homeobox1 (MSX1), encoding transcription factors that earlier studies found were involved in the manifestation of this condition. No specific causative mutation was found. However, we detected a C→T change in MSX1 exon 2 in both twins, suggesting that this polymorphism might be involved in the trait's expression.

Background and objective: Intrauterine growth restriction (IUGR) may be associated with significantly higher aortic intima–media thickening (aIMT) values. It is unknown if fetal aIMT is associated with glomerulosclerosis and amniotic albuminuria in utero. Design, setting, participants, and measurements: Fetal abdominal aIMT and amniotic albumin/creatinine ratio (ACR) were measured in 126 individual twin fetuses, recruited by the Obstetrics and Gynaecology Clinics of the University of Padua (Italy) Medical Center. The IUGR twin fetuses were classified into two groups: Group A were those fetuses whose estimated fetal weight (EFW) was <10th percentile with pulsatility index >2 SD and Group B were those fetuses whose EFW was <10th percentile and had no velocimetry abnormalities. Results: The median fetal aIMT was significantly different in the three groups (Group A = 0.9 mm; Group B = 0.7 mm; and appropriate for gestational age (AGA) = 0.5 mm; p < .0001). It was significantly higher in Group A than in the AGA group (p < .0001) and than in the Group B fetuses (p = .003), respectively. In addition, ACR was different in the three groups (Group A = 183,500 mg/g; Group B = 6,4720 mg/g; and AGA = 8,2750 mg/g; p = .0002). It was significantly higher in Group A than in the AGA group (p = .03) and than in Group B (p = .02), respectively. Conclusions: Growth-restricted twin fetuses with velocimetry abnormalities present are associated with aIMT and higher ACR levels in amniotic fluid, which could be possible markers in utero of preclinical atherosclerosis, and early glomerulosclerosis.

The University of British Columbia (UBC) Twin Project is a registry of approximately 2,000 pairs of reared-together twins recruited across the major Canadian provinces. The focus of the project is an investigation of the behavioral genetics of personality and its disorders, and their relationship to other forms of mental illness. The goal is to find evidence for current diagnostic structures and classification systems, or certainly provide data for their reform. The primary measures employed are full-form self-report questionnaires of major psychological and psychiatric instruments covering personality, mood, general health, schizotypy, and more recently the anxiety disorders from symptoms resulting from exposure traumatic events, obsessive–compulsive behavior and beliefs, as well as coping strategies and health anxieties. No DNA has been collected. Data from the project have been used in several collaborative projects worldwide, and collaborative projects with other groups and interested researchers are welcomed.

Information on multiple deliveries with regard to Portugal is scarce. Based on data provided by the Portuguese Institute of Statistics (INE), the rates for double and triple deliveries were calculated since 1930. The results obtained show for twins a uniform temporal pattern up to the 1970s. At this time rates decreased, but later they gradually recovered, reaching their maximum level in 2010. For triplets, the highest rates occurred between 1999 and 2002. For the period 1988–2011, the rates of multiple deliveries were related to a set of variables recorded in the INE database on live births. Significant differences (p < .001) between simple and multiple deliveries were obtained for maternal age, parity and marital status. Considering the year when the delivery occurred, significant differences (p < .001) persisted for maternal age regardless of the year. For the type of mating, significance was consistently found since the year 2002 (either by using the marital or the cohabitation criteria), and for parity since 2003. With regard to territorial variation, throughout seven periods between 1930 and 2011, the rates among the 20 administrative Portuguese territories, including the two insular districts of Açores and Madeira, were mostly stable for twinning rates, with a minimum level in 1970–1989. Regarding triplets, the greatest inter-district variation was found after 1980. The results of the Portuguese study on multiple deliveries are interpreted in the context of the Iberian Peninsula based on findings reported for Spain.

Fumarase deficiency is a rare autosomal recessive inborn error of metabolism of the Krebs Tricarboxylic Acid cycle. A heavy neurological disease burden is imparted by fumarase deficiency, commonly manifesting as microcephaly, dystonia, global developmental delay, seizures, and lethality in the infantile period. Heterozygous carriers also carry an increased risk of developing hereditary leiomyomatosis and renal cell carcinoma. We describe a non-consanguineous family in whom a dichorionic diamniotic twin pregnancy resulted in twin boys with fumarase deficiency proven at the biochemical, enzymatic, and molecular levels. Their clinical phenotype included hepatic involvement. A novel mutation in the fumarate hydratase gene was identified in this family.

Objective: To evaluate the perinatal outcome of intrauterine growth-restricted preterm twins and contribution of prematurity to morbidity and mortality. Study design: A case–control study of 211 preterm twins: 108 growth-restricted twins matched with 103 normal growth twins of the same gestational age. Mortality and morbidity rates were compared between groups. Result: Fetal and overall perinatal mortality rates of growth-restricted fetuses were higher than normal growth ones. Respiratory distress syndrome incidence was lower and neurologic sequelae incidence higher in growth-restricted twins. No differences were observed between groups with respect to neonatal mortality, low Apgar score, neonatal intensive care unit admission, periventricular hemorrhage, sepsis, jaundice, and hematologic or metabolic disorders. Conclusion: Adverse perinatal outcomes of preterm twins complicated with intrauterine growth restriction are represented by a higher antepartum mortality rate, but once born alive, neonatal outcomes seem to be associated only with gestational age at birth, excluding a protective effect on lung maturation and a higher risk of long-term neurologic sequelae.

High-resolution genomic tests have the potential to revolutionize healthcare by vastly improving mutation detection. The use of chromosomal microarray (CMA) represents one of the earliest examples of these new genomic tests being introduced and disseminated in the clinic. While CMA has clear advantages over traditional karyotyping in terms of mutation detection, little research has investigated the process by which CMA was implemented in clinical settings. Fifteen key informants, six clinicians, and nine laboratory scientists from four Australian states were interviewed about their experiences during and in the time since CMA was adopted for clinical use. Participants discussed challenges such as result interpretation and communication. Strengths were also highlighted, including the collaborative approaches of some centers. Clinical experiences and opinions can inform larger studies with a range of stakeholders, including patients. The historical perspectives from this retrospective study can be helpful in guiding the implementation of future genomic technologies such as whole exome/genome sequencing.

Twin studies are extremely useful for investigating hypotheses of genetic influence on a range of behavioral and physical traits in humans. Studies of physical traits, however, are usually limited to size-related biological characteristics because it is inherently difficult to quantify the morphological counterpart – shape. In recent years, the development of geometry-preserving analytical techniques built upon multivariate statistical methodologies has produced a new discipline in biological shape analysis known as geometric morphometrics. In this study of hand shape analysis, we introduce the reader already familiar with the field of twin research to the potential utility of geometric morphometrics and demonstrate the cross-discipline applicability of methods. We also investigate and compare the efficacy of the 2D:4D ratio, a commonly used marker of sexual dimorphism, to the fully multivariate approach of shape analysis in discriminating between male and female sex. Studies of biological shape variation utilizing geometric morphometric techniques may be completed with software freely available on the Internet and time invested to master the small learning curve in concepts and theory.

The Guangzhou Twin Registry is a population-based registry of twins residing in Guangzhou City. The initial registry database included 9,700 pairs of young twins recruited from the Official Household Registry of Guangzhou City. The registry is designed to provide a resource to identify the genetic and environmental causes of common diseases with an initial focus on eye diseases. From 2006 onward, phenotype and DNA collection have been completed for more than 1,200 twin pairs and their parents or siblings. Most of the young twins have come back for an annual examination of the progressive traits, such as refraction, ocular biometry, weight, and height. Genome-wide association scans have been completed recently. This article gives an update of the study design, cohort profile, previous findings, and future directions. Results from the Guangzhou Twin Project may contribute to the understanding of gene-environmental interplay for complex diseases in both adults and children.