We examined the contributions of genetic and environmental factors to body mass index (BMI) over approximately 28 years. Participants were 693 male, predominantly middle-class, twins (355 monozygotic, 338 dizygotic) from the Vietnam Era Twin Registry. The phenotypic correlation between age 20 and age 48 BMI was 0.52; the genetic correlation was 0.60. Most of the remaining variance at both times was accounted for by nonshared environmental factors. Since genetic factors are not perfectly correlated, this indicates that other genes affect BMI at one or both time points, leaving room for further exploration of the genetics of body mass stability. Mean BMI increased significantly from 22.7 (normal) to 27.8 (overweight). Overweight BMI at age 20 predicted midlife adult onset diabetes (adjusted odds ratio = 4.62, 95% CI 1.91 to 11.18), but not hypertension. Depending on one's vantage point, the results indicate elements of both stability and change in BMI. Very similar phenotypic and genetic correlations were observed over a similar time period in a WW II twin sample, but without the substantial mean increase in BMI. It seems unlikely that different genes influence BMI in the two cohorts. Therefore, we argue that nonshared environmental factors are probably primarily responsible for the secular increase in midlife BMI. Our results also provide prospective evidence that early excess BMI may have serious long-term health consequences, and that this risk is not limited to minorities or adults of lower socioeconomic status.

The objective of this study was to examine the heritability of an endophenotype relevant to nicotine dependence, namely tension reduction after smoking. This study also examined whether common genetic, shared environmental, and nonshared environmental factors influence this endophenotype measured repeatedly during an experimental paradigm. Twin and sibling pairs, all of whom were regular smokers, completed a laboratory paradigm in which they reported on levels of tension at baseline and after smoking each of 3 cigarettes. Univariate twin analyses suggested a sizeable role of additive genetic effects on tension reduction, with heritability estimates ranging between 47 and 68%. Result of multivariate Cholesky analyses indicated that there were additive genetic influences common to tension reduction assessed after cigarettes 1, 2, and 3. Multivariate models including genetic and nonshared environmental effects provided the best fit to the data. To the best of our knowledge, this is the first study to examine the genetic basis of a laboratory smoking endophenotype, in this case tension reduction after smoking. Implications for genetic association studies are discussed.

Quantitative and molecular genetic research requires large samples to provide adequate statistical power, but it is expensive to test large samples in person, especially when the participants are widely distributed geographically. Increasing access to inexpensive and fast Internet connections makes it possible to test large samples efficiently and economically online. Reliability and validity of Internet testing for cognitive ability have not been previously reported; these issues are especially pertinent for testing children. We developed Internet versions of reading, language, mathematics and general cognitive ability tests and investigated their reliability and validity for 10- and 12-year-old children. We tested online more than 2500 pairs of 10-year-old twins and compared their scores to similar internet-based measures administered online to a subsample of the children when they were 12 years old (> 759 pairs). Within 3 months of the online testing at 12 years, we administered standard paper and pencil versions of the reading and mathematics tests in person to 30 children (15 pairs of twins). Scores on Internet-based measures at 10 and 12 years correlated .63 on average across the two years, suggesting substantial stability and high reliability. Correlations of about .80 between Internet measures and in-person testing suggest excellent validity. In addition, the comparison of the internet-based measures to ratings from teachers based on criteria from the UK National Curriculum suggests good concurrent validity for these tests. We conclude that Internet testing can be reliable and valid for collecting cognitive test data on large samples even for children as young as 10 years.

People differ markedly in their risk for developing posttraumatic stress symptoms (PTSS) after exposure to traumatic events. Twin studies suggest that the trauma-PTSS relationship is moderated by genetic and environmental influences. The present study tested for specific types of genetic and environmental interaction effects on PTSS. A sample of 222 monozygotic and 184 dizygotic twin pairs reported on lifetime frequency of assaultive and nonassaultive trauma and associated PTSS. Biometric analyses indicated that in the case of nonassaultive trauma, PTSS were directly affected by environmental factors that also influence exposure to nonassaultive trauma. For assaultive trauma both genetic and non-shared environmental influences jointly affected PTSS, and the number of traumatic events moderated the severity of PTSS. Genetic factors were found to become less important beyond some threshold (e.g., 3 or 4 types of serious trauma) suggesting that genetic factors — which may confer either risk or resilience to PTSS — modify these symptoms within a range of human experience, beyond which environmental effects supervene.

This article analyzes the effect of classroom separation of twins on their cognitive abilities, measured at different ages in Dutch primary education. We use a large longitudinal school-based sample of twins and their classmates. The analysis tries to reduce the bias by unobserved factors due to the nonrandom assignment of twins by taking into account differences in school environment, previous test scores and variation in class assignment between years. We find that classroom separation matters for language in Grade 2. Nonseparated twins score higher on language, and the difference is larger for same-sex pairs. This finding is robust for various methods that take unobserved effects into account. In addition, there is some evidence for higher scores in arithmetic in Grade 2. For the higher grades we find no effect of classroom separation on cognitive ability. In the analysis of the effect of a separation of at least 3 years we find that separation increases language performance between Grade 6 and 8 for opposite-sex pairs.

It has been shown that lower birthweight is associated with lower IQ, but it remains unclear whether this association is causal or spurious. We examined the relationship between birthweight and IQ in two prospective longitudinal birth cohorts: a UK cohort of 1116 twin pairs (563 monozygotic [MZ] pairs), born in 1994–95, and a New Zealand cohort of 1037 singletons born in 1972–73. IQ was tested with the Wechsler Intelligence Scales for Children. Birthweight differences within MZ twin pairs predicted IQ differences within pairs, ruling out genetic and shared environmental explanations for the association. Birthweight predicted IQ similarly in the twin and nontwin cohorts after controlling for social disadvantage, attesting that the association generalized beyond twins. An increase of 1000 g in birthweight was associated with a 3 IQ point increase. Results from two cohorts add to evidence that low birthweight is a risk factor for compromised neurological health. Our finding that birthweight differences predict IQ differences within MZ twin pairs provides new evidence that the mechanism can be narrowed to an environmental effect during pregnancy, rather than any familial environmental influence shared by siblings, or genes. With the increasing numbers of low-birthweight infants, our results support the contention that birthweight could be a target for early preventive intervention to reduce the number of children with compromised IQ.

Previous research has demonstrated a link between attention-deficit/hyperactivity disorder (ADHD), developmental coordination disorder (DCD), and depression. The present study utilized a monozygotic (MZ) differences design to investigate differences in depressive symptomatology between MZ twins discordant for ADHD or DCD. This extends previous research as it controls for genetic effects and shared environmental influences and enables the investigation of nonshared environmental influences. In addition, children and adolescents with comorbid ADHD and DCD were compared on their level of depressive symptomatology to those with ADHD only, DCD only, and no ADHD or DCD. The parent-rated Strengths and Weaknesses of ADHD Symptoms and Normal Behavior, Developmental Coordination Disorder Questionnaire, and Sad Affect Scale were used to assess ADHD, DCD, and depressive symptomatology respectively. The results revealed higher levels of depressive symptomatology in MZ twins with ADHD or DCD compared to their nonaffected co-twins. In addition, children and adolescents with comorbid ADHD and DCD demonstrated higher levels of depressive symptomatology compared to those with ADHD only, DCD only, and no ADHD or DCD. The implications of these findings are discussed with emphasis on understanding and recognizing the relationship between ADHD, DCD, and depression in the assessment and intervention for children and adolescents with these disorders.

Twinning rates have changed substantially over time for reasons that are only partly known. In this study we studied smoking, coffee and alcohol intake, and their possible interaction with obesity as potential determinants of twinning rates using data from the Danish National Birth Cohort between 1996 and 2002. We identified 82,985 pregnancies: 81,954 singleton and 1031 twins. For the twins we had data to classify 121 as monozygotic, 189 dizygotic (same sex), 313 dizygotic (opposite sex) but, 408 were of the same sex but with unknown zygosity. All mothers were interviewed about their prepregnancy weight and height, coffee and alcohol intake, smoking habits, and potential confounding factors at early stages of pregnancy. We identified smoking (> 10 cigarettes/day) as a possible determinant of twinning, particularly for dizygotic twinning rates (same sex) and furthermore corroborated that obesity and the mother's age are strong correlates of twinning. Others have found coffee intake to increase twinning rates but that is not seen in these data.

A requirement for performing robust genetic and statistical analyses on twins is correctly assigned zygosities. In order to increase the power to detect small risk factors of disease, zygosity testing should also be amenable for high throughput screening. In this study we validate and implement the use of a panel of 50 single nucleotide polymorphisms (SNPs) for reliable high throughput zygosity testing and compare it to a panel of 16 short tandem repeats (STRs). We genotyped both genomic (gDNA) and whole genome amplified DNA (WGA DNA), ending up with 47 SNP and 11 STR markers fulfilling our quality criteria. Out of 99 studied twin pairs, 2 were assigned a different zygosity using SNP and STR data as compared to self reported zygosity in a questionnaire. We also performed a sensitivity analysis based on simulated data where we evaluated the effects of genotyping error, shifts in allele frequencies and missing data on the qualitative zygosity assignments. The frequency of false positives was less than 0.01 when assuming a 1% genotyping error, a decrease of 10% of the observed minor allele frequency compared to the actual values and up to 10 missing markers. The SNP markers were also successfully genotyped on both gDNA and WGA DNA from whole blood, saliva and filter paper. In conclusion, we validate a robust panel of 47 highly multiplexed SNPs that provide reliable and high quality data on a range of different DNA templates.

After a long continuous decrease, the twinning and higher multifetal rates in many developed countries have increased during the last 2 to 3 decades. This change has been attributed to delayed childbearing and to increased use of subfertility treatments, particularly in women over 35 years of age. In this study we analyze how these new trends depend on changes in the effect of maternal age on the rates of multiple maternities. Our study is based on data for England and Wales for the period 1938 to 2003. The temporal variations show a decreasing trend to a trough around 1980 and after that a steady increase. This increase was more marked for higher multifetal rates and was particularly high for quadruplets. Furthermore, we identified changes in the age-specific rates resulting in increased levels for older mothers. These findings are in good agreement with our results from Nordic populations.

Based on the birth record data from the National Vital Statistics in the 1990 Census of China, the present study analyzed the differences between urban and rural areas on monozygotic (MZ) and dizygotic (DZ) twin rates by maternal age in 1989. The twins by zygosity were calculated with Weinberg's differential method. Results show that the MZ and DZ twinning rates in China were associated with maternal age and that there were substantial differences between urban and rural areas. The MZ twinning rates in urban and rural areas were 2.36 pairs and 2.11 pairs per 1000 deliveries respectively, significantly lower than that in most studied populations. Furthermore, our analysis indicated that MZ twinning rates remained relatively constant for mothers under the age group of 36 to 38 years, but rose over this age group in both areas, albeit with a different slope. The DZ twinning rates were strikingly affected by maternal age, but the age for peak DZ rates was found within the age group of 33 to 35 years. In all maternal age groups except for 24 to 26 years, the DZ twinning rates in urban areas were higher than in rural areas. It remains unclear as to why the DZ twinning rates reversed to reach higher values within the older maternal age groups in China, but it is almost certain that the high twinning rates had nothing to do with in vitro fertilization.

Frequencies of recurrent multiple maternities were estimated using two sets of census data in Japan in 1990 and 1995. The repeat frequency (RF) of the twinning rate is the frequency of 2 sets of twins among families or couples who have already had 1 set of twins and 2 more siblings. The overall RFs were 9.6 per 1000 couples in 1990 and 9.3 in 1995. The RFs of the monozygotic (MZ) twinning rates were 5.9 per 1000 couples in 1990 and 5.5 in 1995. The RFs of the dizygotic (DZ) twinning rates were 3.7 in 1990 and 3.8 in 1995. For unlike-sexed propositus twins, the RF of MZ twins were 5.0 per 1000 couples in 1990 and 5.5 in 1995. The RF of DZ twins were 5.3 in 1990 and 4.6 in 1995. As for like-sexed propositus twins, the corresponding RFs were 6.2 and 5.5 for MZ twins, and 3.4 and 3.6 for DZ twins, respectively. In mothers who have experienced a twin maternity, the overall RF of twinning was 1.5 to 2 times as high as the average mother's chance of having twins. There was no RF for triplets for both census years. As for geographic variations of the overall RF, the rates in Okinawa (16.2) and Hokkaido (15.3) were significantly higher than those in the Tohoku (8.7), Kanto (8.0) and Kyushu (7.4) districts.

Twins compared with singletons and monozygous (MZ) compared with dizygous (DZ) twins are at increased risk of fetal and infant death, cerebral palsy and many congenital anomalies. The aim of this study is to investigate whether zygosity is a risk factor for the sudden infant death syndrome (SIDS). Birth registration data and draft infant death certificates for all multiple births in England and Wales 1993 to 2003 were provided by the Office for National Statistics. As a partial proxy for zygosity, same-sex was compared with opposite-sex twins for birthweight-specific mortality and mortality attributed to SIDS. Data on singleton infants were obtained by subtraction of multiple births from routinely published population births and infant deaths. SIDS mortality among low birthweight infants was significantly less in twins than singletons. The twin-singleton relative risk was reversed in infants of normal birthweight. Among infants of normal birthweight, neonatal SIDS was significantly more common in same- compared with opposite-sex pairs. Among infants of low birthweight, postneonatal SIDS was significantly more common in same- compared with opposite-sex pairs. The difference in birthweight distribution of same- compared with opposite-sex twins for neonatal SIDS suggests that zygosity is a risk factor for SIDS. As congenital cerebral anomalies are a feature of many monozygous twin conceptions, a detailed macro- and microscopical examination of the brain in twin SIDS may indicate an otherwise unrecognised pathology.

The aim was to study the effect of twin gestations in a uterus with 2 bodies on the probability of breech presentation at delivery. The hypothesis was that the probability of breech presentation was not higher than 50%. A review was undertaken of MEDLINE (1966–2004) and of the article reference list for statistical analysis of presentation at delivery among twins in a normal uterus, singleton gestations in a uterus with 2 bodies, and case studies of twins in a uterus with 2 bodies. There are 10 studies of twin gestations in a normal uterus (Twin A 3036 cases, breech presentation 22.36%; Twin B 2758 cases, breech presentation 36.87%), 2 studies of singleton gestations in a uterus with 2 bodies (297 cases, breech presentation 42.09%), and 57 case report studies of twin gestations in a uterus with 2 bodies (Twin A 56 cases, breech presentation 14.29%; Twin B 54 cases, breech presentation 18.52%). The odds ratio and chi-square test for differences in probabilities show a significantly lower incidence of breech presentation for twins in a uterus with 2 bodies compared with twins in a normal uterus (Twin A, odds ratio = 0.58; χ2 = 2.08, p > .05, Twin B, odds ratio = 0.39, χ2 = 7.67, p < .05), and singleton gestations in a uterus with 2 bodies (Twin A, odds ratio = 0.23, χ2 = 15.51, p < .05; Twin B, odds ratio = 0.31, χ2 = 10.72, p < .05). Twin gestations in a uterus with 2 bodies decrease the probability of breech presentation.

In a previously published article (Resta et al., 2006) on Robert's syndrome in prenatal diagnosis, a case of a 36-year-old woman and her 36-year-old, nonconsanguineous husband were presented. Our findings suggest the existence of nonsense mediated decay (NMD) variability which could account for the varying severity reported in carriers of identical mutations. Furthermore, fetal cells were used to evaluate the influence of premature centromere separation (PCS) on the sister chromatid exchange (SCE) and micronucleus (MN) frequency. Given the similar variation observed in the SCE frequencies, dependent on tissue/cell type (amniotic fluid sample, chorionic villus sampling) and duration of in vitro cultures (48 hours or 72 hours), the idea was that this new piece of information could be interesting. It seems that the SCE frequency increased proportionally to the cell cycle increasing (1° < 2° < 3° … n). Obviously, our observations are too scarce to draw conclusions, but further investigation could be useful to corroborate or dispute these results, considering that the two techniques, (MN and SCE), are simple to perform and do not require expensive laboratory equipment.

Some legal and social complications that arise when identical twins have children are examined. The specific case presented concerns assignment of paternity. This section is followed by a review of recent studies of multiple birth pregnancy risk factors, namely mother to infant HIV transmission and congenital hypothyroidism. Honors given to recently recognized twin researchers are noted, as is the birth of twins to an older mother in the United States.