Information about linkage disequilibrium (LD) is important in understanding the genome structure and has its applications in association studies. Here we present the first genome-wide LD study based on a founder population (East Finland). The LD data consist of 118 unrelated individuals and around 480,000 SNP pairs genotyped with the Affymetrix 100K genotyping assay. Using the minor allele frequency (MAF) limit of .05, the squared correlation coefficient between two loci (r2) was .48, .37, .28, and .20 for distances of 5, 10, 20, and 40 kb respectively. MAF had a significant effect on the mean r2 so that the extent of useful LD (r2 > .3) varied from 17 kb to 80 kb depending on the limit set for the MAF. For D' the effect of MAF was smaller but reflected the possible age of the mutation: SNPs with high MAF had lower D' than those with low MAF. The X chromosome showed higher D' values than autosomes and the extent of useful LD (r2 > .3) was twice as long on the X chromosome than on the autosomes. Based on the results, LD varies across the genome and is correlated to local recombination rate between and within chromosomes. However, the recombination rate does not explain all the variation found in LD. We also report a number of long chromosomal regions where exceptionally high or low LD were detected.

The first classical twin studies, recognizing the potential of comparing findings in identical twins, have previously been reported to be those by Siemens and by Merriman, both published in 1924. However, we would like to bring to attention a study performed by Walter Jablonski, 2 years earlier (1922), investigating the contribution of heredity to refraction in human eyes. Jablonski examined the eyes of 52 twin pairs and by comparing the size of within-pair differences between identical and non- identical twins was able to infer the heritability of a trait. Therefore, this is likely to be the first reported classical twin study.

The classical twin design (CTD) is the most common method used to infer genetic and environmental causes of phenotypic variation. As has long been acknowledged, different combinations of the common environment/assortative mating, and additive, dominant, and epistatic genetic effects can lead to the same observed covariation between twin pairs, meaning that there is an inherent indeterminacy in parameter estimates arising from the CTD. The CTD circumvents this indeterminacy by assuming that higher-order epistasis is negligible and that the effects of either dominant genetic variation or the common environment are nonexistent. These assumptions, however, lead to consistent biases in parameter estimation. The current paper quantifies these biases and discusses alternative strategies for dealing with parameter indeterminacy in twin designs. One strategy is to model the similarity among other relatives in addition to twins (extended twin-family designs), which reduces but does not eliminate indeterminacy in parameter estimates. A more general strategy, applicable to all twin designs, is to present the parameter indeterminacy explicitly, as in a graph. Presenting the space of mathematically equally likely parameter values is important, not only because it aids the proper interpretation of twin design findings, but also because it keeps behavioral geneticists themselves mindful of methodological assumptions that can easily go unexamined.

The classical twin design (CTD) circumvents parameter indeterminacy by assuming (1) negligible higher-order epistasis; and (2) either nonadditive genetic or common environmental effects are nonexistent, creating two potential sources of bias (Eaves et al., 1978; Grayson, 1989). Because the extended twin-family design (ETFD) uses many more unique covariance observations to estimate parameters, common environmental and nonadditive genetic parameters can be simultaneously estimated. The ETFD thereby corrects for what is likely to be the largest of the two sources of bias in CTD parameter estimates (Keller & Coventry, 2005). In the current paper, we assess the extent of this and other potential sources of bias in the CTD by comparing all published ETFD parameter estimates to CTD parameter estimates derived from the same data. CTD estimates of the common environment were lower than ETFD estimates of the common environment for some phenotypes, but for other phenotypes (e.g., stature in females and certain social attitudes), what appeared as the common environment was resolved to be assortative mating in the ETFD. On average, CTD estimates of nonadditive genetic factors were 43% lower, and additive genetic factors 63% higher, than ETFD estimates. However, broad-sense heritability estimates from the CTD were only 18% higher than ETFD estimates, highlighting that the CTD is useful for estimating broad-sense but not narrow-sense heritability. These results suggest that CTD estimates can be misleading when interpreted literally, but useful, albeit coarse, when interpreted properly.

Twin studies that examine the effect of specific environmental risk factors on psychiatric disorders assume that there are no differences in prevalences of these risk factors between twins and singletons. Violation of this assumption signifies that the results from twin studies might not generalize to singletons. Another assumption, not only often underlying twin studies but also epidemiological research, is that life- events are not influenced by familial factors. We tested differences in prevalences of experienced life events in a Dutch sample of 2086 monozygotic (MZ) twins, 2090 dizygotic (DZ) twins and 1307 of their siblings. Self-reported data on life events (illness of self, illness of a significant other, spouse/romantic relationship, divorce/break-up of a relationship, death of a significant other, traffic accident, robbery, violent assault, sexual assault) were available from a survey- study. We further investigated whether familial resemblance was present for the exposure to these life events and, if so, whether this resemblance was due to genetic or common environmental factors. No differences were found in the prevalences of life events between MZ twins, DZ twins and their siblings. There was evidence for familial aggregation of all life events, except for traffic accidents in women. Results indicated genetic control on the presence of a spouse or involvement in a relationship. Familial resemblance of illness and death of a significant other was mainly due to common environment. For the other life events, it was not possible to distinguish between genetic and common environmental effects.

The role of co-twin dependence (twins' closeness or reliance on the co-twin) was examined as a moderator of genetic and environmental influences on alcohol use in adolescence and early adulthood in a large longitudinal population-based study of Finnish twins (FinnTwin16). The associations between co-twin dependence and alcohol use were studied first at an individual level in adolescence (n = 3362) and early adulthood (n = 2912). Then, maximum likelihood models were fit to the two waves of data from same-sex twin pairs to assess the differences and changes in genetic and environmental influences on alcohol use (abstinence, drinking frequency, intoxication frequency); N = 1342 pairs in adolescence, and N = 1078 pairs in early adulthood. Overall, no significant associations were found between co-twin dependence and individual alcohol use. However, co-twin dependence importantly modulated genetic effects on drinking habits, especially in adolescence, but also in early adulthood. Co-twin–dependent twins reported greater similarity in their alcohol-related behavior across all alcohol-use measures at both time points, and the role of genes and environments varied according to co-twin dependence. Shared environmental factors explained most of the variation in drinking among co- twin–dependent twins in adolescence and contributed to drinking to intoxication during early adulthood. In contrast, among co-twin–independent twin pairs, genetic variance contributed significantly to all alcohol-use measures at both time-points. An interdependent sibling relationship is an important modifier of drinking habits, and it appears to reduce the impact of inherited liabilities on alcohol-related behavior especially in adolescence.

We investigated the genetic component of noise sensitivity using a twin-study design. The study sample consisted of 573 same-sexed twin pairs from the Finnish Twin Cohort. The 131 monozygotic (MZ) and 442 dizygotic (DZ) twin pairs with an age range of 31 to 88 years replied to a questionnaire on noise and health-related items in 1988. The noise sensitivity of respondents was defined as high, quite high, quite low or low. MZ pairs were more similar with regards noise sensitivity than DZ pairs, and quantitative genetic modeling indicated significant familiality. The best z-fitting genetic model provided an estimate of heritability of 36% (95% CI = .20–.50) and when hearing impaired subjects were excluded this rose to 40% (95% CI = .24–.54). In conclusion, noise sensitivity does aggregate in families and probably has a genetic component.

This study examined the association between early child care on the development of behavior problems. At the age of 5 years, child care information was collected from parents on a large group of twins who were born between 1985 and 1997. Mothers and fathers rated the behavior of the child at ages 3, 7, and 10 years using the Child Behavior Checklist (CBCL) and teachers reported on the same children's behaviors using the Teacher's Report Form (TRF) at ages 7 and 10. At the age of 3 years, children with nonparental child care experiences had more externalizing problems than children with only parental child care. The long-term effects of quantity of child care were mixed and were only significant for mother ratings and for children from families with a low socioeconomic status. Overall, the effect sizes of child care were very small (effect sizes were between .12 and .23). Children with a larger amount of child care did not show more behavior problems, therefore it was questioned whether the increased levels of behavior problems could be attributed to quantity of child care.

The aim of this study was to determine the accuracy of sonographic chorionicity determination in the largest sample of twin pregnancies to date. We retrospectively analyzed 463 twin pregnancies delivered over a 6-year period to determine in each case what the antenatal sonographic prediction of chorionicity was, and then what the subsequent post partum pathological diagnosis of chorionicity was. Out of 436 twin pregnancies, 428 were correctly diagnosed for chorionicity as confirmed by pathology reports. Sonography as a screening tool for monochorionic twin pregnancies has a sensitivity of 100%, a specificity of 97.9% and a predictive value positive of 88.2%. Transvaginal scanning in the first trimester determined twin chorionicity with a sensitivity and a specificity of 100%. This study has confirmed in the largest sample to date that sono- graphic chorionicity determination is best done in the first trimester using vaginal scans, where it has 100% accuracy.

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 the study was to test the hypothesis that changes in arm anthropometry can be used to determine the risk of faltering growth in twin gestations. Serial data on midupper arm circumference (MUAC) and maternal weight gain were collected from a sample of 156 mothers. Changes in MUAC were monitored from 20 to 34 weeks. Women with a large loss of MUAC (greater than 1.5 cm), particularly when it occurred within two to four weeks of delivery, were significantly heavier, had higher pregravid Body Mass Indexes (BMIs), but gained less weight than mothers with no change in MUAC. In analysis of covariance models adjusting for length of gestation, black ethnicity, males per twin pair, monochorionicity, and baseline MUAC at 20 weeks, a large loss of MUAC was associated with significantly lower birthweight (2263 g vs. 2499 g) and birthweight z-score (–0.92 SDU vs. –0.39 SDU). Changes in MUAC from 20 to 34 weeks, and especially near delivery, are significantly associated with fetal growth in twin pregnancies. A positive change may indicate that the mother has adequate dietary intake or nutrient stores to continue to accrue lean body mass and support fetal growth, while a loss of MUAC indicates that dietary intake or nutrient stores may be inadequate. This simple, relatively precise, measure of change in maternal body composition during pregnancy may be useful in identifying twin pregnancies at risk for faltering intrauterine growth, particularly among overweight or obese women.

This month's News, Views and Comments column differs from those that have appeared in previous issues. The first of the companion papers presented here offers the first in-depth historical overview of Dr. Peter Neubauer's controversial study of infant identical twins separated at birth, launched in the 1950s. The author, Dr. Lawrence Perlman, was a research assistant on the project while earning his doctoral degree in clinical psychology from New York University. His paper is followed by my own critical appraisal of issues raised by that study, some of which are still timely today. Readers are invited to forward their comments to me ([email protected]) for possible consideration in future columns of Twin Research and Human Genetics.