Twin research : the official journal of the International Society for Twin Studies最新文献

This paper examines why parents of twins or adult twins themselves request zygosity testing. Of 405 multiples including 8 sets of triplets, the majority (93%) were monozygotic. Age of testing ranged from 0 days to 73 years. About 50% of requests came from parents or twins who were curious about, or expressed a need to be certain of, their zygosity. Other reasons included health concerns (current or future), other twins in the family, and misinformation about zygosity, frequently because of the erroneous assumption that all dichorionic twins are dizygotic. Parents of monozygotic twins may expect their twins to be 'identical' and believe their twins to be dizygotic because of minor phenotypic differences between them. Dizygotic twins like other siblings may share a phenotypic resemblance. Health professionals should be aware that zygosity of multiples may not always be obvious to parents and that accurate knowledge of zygosity may be justified.

Weight discordance is very rare in monozygotic (MZ) twin pairs; when found, however, such pairs are advantageous in the search for either environmental or epigenetic causes and consequences of obesity. We analyzed the growth patterns of young adult MZ pairs discordant and concordant for obesity. Screening 5 consecutive birth cohorts (1975-1979) of 22- to 27-year-old Finnish twins (the FinnTwin16 study), we found 14 obesity discordant (Body Mass Index [BMI] difference > or = 4 kg/m2) MZ pairs out of 658. Ten pairs participated in clinical studies. Nine concordant pairs (BMI difference < or = 2 kg/m2) were examined as controls. Lifetime measured heights and weights recorded in hospitals and health centers were traced manually. Height development was similar in all the co-twins of both groups. The weight differences between the co-twins of the discordant pairs began to emerge at 18 years leading to an average discordance of 16.4 kg, 5.6 kg/m2 (p for both = .005) at 25.7 years. The heavier co-twin weighed 221 g (p = .066), 1.0 kg/m2 (p = .01) more already at birth than the leaner, but the differences waned by 6 months of age and reappeared only after adolescence. Both the leaner and the heavier co-twins of the discordant pairs weighed more than expected by the singleton reference values (Cole et al., 1998) after 8 years. The concordant co-twins, on the other hand, grew similarly and after 6 months, their mean growth was not distinguishable from the singleton patterns. Young adulthood represents a critical period of gaining weight irrespective of genetic background in this twin sample.

A multicategory item-response theory model was developed to characterize developmental changes in three items relating to the assessment of puberty in adolescent twin girls and boys. The model allowed for the fixed effects of age on probability of endorsing the responses and for the random effects of individual differences on the timing of pubertal changes relative to chronological age. In girls, the model was applied three-wave data on twin pairs (N = 414 female monozygotic [MZ] and 197 female dizygotic [DZ] pairs) and female twins from boy-girl pairs (N = 300 twins) from the Virginia Twin Study of Adolescent Behavioral Development. In boys, the data comprised 318 MZ and 185 DZ pairs and 297 male twins from boy-girl pairs. A total of 3172 and 2790 individual twin assessments were available in girls and boys, respectively, spanning ages 8-17 years. The availability of twin data allows the contributions of genes, the shared environment and individual unique environmental experiences to be resolved in the relative timing of pubertal changes. Parameters of the mixed model including fixed effects of age and random effects of genes and environment were estimated by Markov Chain Monte Carlo simulations using the BUGS algorithm for Gibbs sampling. The estimated standard deviation of random differences in the timing of puberty relative to age was 0.96 years in girls and 1.01 years in boys. The estimated intraclass correlations for the relative timing of pubertal changes were 0.99 +/-0.01 in MZ girls, 0.52 +/-0.02 in DZ girls, 0.88 +/-0.04 in MZ boys and 0.44+/-0.02 in DZ boys, indicating a very large contribution of genetic factors to the relative timing of pubertal change in both sexes. Additive genetic factors account for an estimated 96.3+/-3.3% of the total variance in random effects in girls and 88.0+/-3.6% in boys. Shared environmental influences account for 3.6+/-3.4% in girls and 0% in boys. In girls, nonshared environmental effects explain 0.1+/-0.1% of the total residual variance. The comparable figure in boys is 12.0+/-3.6%.

We compared the accuracy of genotyping for DNA extracted from lymphocytes to that of DNA amplified from buccal epithelial cells. Amplification was via a rolling circle/phi29 DNA polymerase commercial kit. Paired buccal and lymphocyte DNA samples were available from 30 individuals. All samples were genotyped for 12 SNPs, 5 microsatellites and 2 VNTRs. The accuracy of genotyping (no-call proportions, reproducibility, and concordance) was similar for DNA from lymphocytes in comparison to amplified DNA from buccal samples. If used with caution, these data suggest that rolling-circle whole-genome amplification can be used to increase the DNA mass available for large-scale genotyping projects based on DNA from buccal cells.

Statistical power of the classical twin design was revisited. The approximate sampling variances of a least-squares estimate of the heritability in a univariate analysis and estimate of the genetic correlation coefficient in a bivariate analysis were derived analytically for the ACE model. Statistical power to detect additive genetic variation under the ACE model was derived analytically for least-squares, goodness-of-fit and maximum likelihood-based test statistics. The noncentrality parameter for the likelihood ratio test statistic is shown to be a simple function of the MZ and DZ intraclass correlation coefficients and the proportion of MZ and DZ twin pairs in the sample. All theoretical results were validated using simulation. The derived expressions can be used to calculate power of the classical twin design in a simple and rapid manner.

Currently, mapping genes for complex human traits relies on two complementary approaches, linkage and association analyses. Both suffer from several methodological and theoretical limitations, which can considerably increase the type-1 error rate and reduce the power to map human quantitative trait loci (QTL). This review focuses on linkage methods for QTL mapping. It summarizes the most common linkage statistics used, namely Haseman-Elston-based methods, variance components, and statistics that condition on trait values. Methods developed more recently that accommodate the X-chromosome, parental imprinting and allelic association in linkage analysis are also summarized. The type-I error rate and power of these methods are discussed. Finally, rough guidelines are provided to help guide the choice of linkage statistics.