Twin Research and Human Genetics最新文献

Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, ZFPM1 (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near FSHB (Follicle Stimulating Hormone beta subunit) and SMAD3 (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus ADRB2 on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).

The circumstances and subsequent life events of the first twins to have been born in different countries are examined. Given that both twins were born in the United Kingdom, their common citizenship was never questioned. In contrast, twins born in Canada to a legally married gay transnational couple - composed of one American and one Israeli - were assigned as citizens of different nations and their parents were regarded as if unmarried. This essay is followed by reviews of research on the Hallermann-Streiff syndrome in monozygotic (MZ) twins, the effects of technology on conjoined twin separation, reciprocal deep inferior epigastric perforator (DIEP) transplantation in MZ twins and new guidelines for managing multifetal pregnancies. Finally, media reports on a book by the world's oldest Auschwitz-Birkenau twin survivor, the passing of Dr Ian Wilmut, the identical twinship of Zhores Medvedev, another case of gay fathers with twin sons, twins and siblings admitted to medical school, and the first and fourth records for major league baseball twins are presented.

Self-perception in early childhood and self-esteem in adulthood are related to a variety of aspects of psychological wellbeing. The goal of the present study was to examine genetic and familial influences on self-perception and self-esteem in separate samples of children (153 twin pairs of 5-year-olds) and adults (753 twin pairs between the ages of 25-75 years). Genetic common factor modeling showed that three facets of self-perception (physical competence, peer acceptance, and maternal acceptance) loaded onto a single heritable factor in children. Multilevel modeling showed no effects of self or co-twin sex on self-perception, but authoritative parenting style was negatively related to self-perception in boys. Similarly, in Study 2, with the adult sample, five self-esteem items loaded on a single heritable factor with no effects of co-twin sex on adult self-esteem. Remembered maternal affection, paternal affection, and maternal discipline were positively related to self-esteem in adults; maternal affection was especially significant for women. The reversal in direction of parenting effects between early childhood and adulthood suggests that parents may play different roles in shaping how children and adults think of themselves. These results suggest that self-perception in childhood and self-esteem in adulthood are both influenced by genetic and environmental factors and that parenting is an important environmental factor for both children and adults.

Phenotypic variation is the result of gene expression based on complex interaction between genetic and environmental factors. It is well known that genetic and environmental factors influence gene expression, but our understanding of their relative importance remains limited. To obtain a hint for the understanding of their contributions, we took advantage of monozygotic twins, as they share genetic and shared environmental factors but differ in nonshared factors, such as environmental differences and stochastic factors. In this study, we performed cap analysis of gene expression on three pairs of twins and clustered each individual based on their expression profiles of annotated genes. The dendrogram of annotated gene transcripts showed a monophyletic clade for each twin pair. We also analyzed the expression of retrotransposons, such as human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs), given their abundance in the genome. Clustering analyses demonstrated that HERV and LINE expression diverged even within monozygotic twin pairs. Thus, HERVs and LINEs are more susceptible to nonshared factors than annotated genes. Motif analysis of differentially expressed annotated genes suggests that specificity protein/Krüppel-like factor family transcription factors are involved in the expression divergence of annotated gene influenced by nonshared factors. Collectively, our findings suggest that expressions of annotated genes and retrotransposons are differently regulated, and that the expression of retrotransposons is more susceptible to nonshared factors than annotated genes.

Astigmatism and myopia are two common ocular refractive errors that can impact daily life, including learning and productivity. Current knowledge suggests that the etiology of these conditions is the result of a complex interplay between genetic and environmental factors. Studies in populations of European ancestry have demonstrated a higher concordance of refractive errors in monozygotic (MZ) twins compared to dizygotic (DZ) twins. However, there is a lack of studies on genetically informative samples of multi-ethnic ancestry. This study aimed to estimate the genetic contribution to astigmatism and myopia in the Mexican population. A sample of 1399 families, including 243 twin pairs and 1156 single twins, completed a medical questionnaire about their own and their co-twin's diagnosis of astigmatism and myopia. Concordance rates for astigmatism and myopia were estimated, and heritability and genetic correlations were determined using a bivariate ACE Cholesky decomposition method, decomposed into A (additive genetic), C (shared environmental) and E (unique environmental) components. The results showed a higher concordance rate for astigmatism and myopia for MZ twins (.74 and .74, respectively) than for DZ twins (.50 and .55). The AE model, instead of the ACE model, best fitted the data. Based on this, heritability estimates were .81 for astigmatism and .81 for myopia, with a cross-trait genetic correlation of rA = .80, nonshared environmental correlation rE = .89, and a phenotypic correlation of rP = .80. These results are consistent with previous findings in other populations, providing evidence for a similar genetic architecture of these conditions in the multi-ethnic Mexican population.

The current study explored the impact of genetic relatedness differences (ΔH) and sample size on the performance of nonclassical ACE models, with a focus on same-sex and opposite-sex twin groups. The ACE model is a statistical model that posits that additive genetic factors (A), common environmental factors (C), and specific (or nonshared) environmental factors plus measurement error (E) account for individual differences in a phenotype. By extending Visscher's (2004) least squares paradigm and conducting simulations, we illustrated how genetic relatedness of same-sex twins (H_SS) influences the statistical power of additive genetic estimates (A), AIC-based model performance, and the frequency of negative estimates. We found that larger H_SS and increased sample sizes were positively associated with increased power to detect additive genetic components and improved model performance, and reduction of negative estimates. We also found that the common solution of fixing the common environment correlation for sex-limited effects to .95 caused slightly worse model performance under most circumstances. Further, negative estimates were shown to be possible and were not always indicative of a failed model, but rather, they sometimes pointed to low power or model misspecification. Researchers using kin pairs with ΔH less than .5 should carefully consider performance implications and conduct comprehensive power analyses. Our findings provide valuable insights and practical guidelines for those working with nontwin kin pairs or situations where zygosity is unavailable, as well as areas for future research.

Fetal sex contributes to the determination of obstetric outcome, as pregnancies carrying male babies seem to have an increased risk of maternal-fetal complications. Most studies have been conducted on singleton pregnancies, whereas less evidence is available for twins. A 10-year retrospective observational study was conducted on a cohort of 1180 women with twin pregnancy delivered at a single tertiary hospital. Clinical data on maternal characteristics, and obstetric and neonatal outcomes were collected, and the analysis was performed on monochorionic (MC) and dichorionic (DC) diamniotic twins separately. The group of DC twins included 837 cases, and those conceived by assisted reproductive technologies (ART) were more likely to have one or both female fetuses rather than males. The incidence of hypertensive disorders of pregnancy (HDP) was higher in same-sex pairs than in opposite-sex pairs. No differences were found regarding other obstetric and neonatal outcomes among the three sex-pairing groups. The MC twins group included 228 cases, and in female-carrying pregnancies a higher incidence of gestational diabetes (GDM) was observed compared to the male group. Furthermore, male pairs had significantly lower Apgar scores than females. Fetal sex seems to have a mild effect in twins compared to singleton pregnancies, suggesting a more complex set of factors contributing to pregnancy outcome in multiple pregnancies. However, we observed a higher incidence of HDP among same-sex DC pairs, a higher rate of GDM among MC female-female pairs, and a worse adaptation to extrauterine life among male-male pairs in MC twins.

A simple model by which Hardy-Weinberg proportions are attained in a single generation while maintaining gene frequencies is stated and illustrated. The title 'Quasi-random mating' is proposed. Confusion about the Hardy-Weinberg principle can be avoided only if there is clear separation between the basic deterministic model and factors influencing a population's structure. Eighty years passed before C. C. Li coined the term 'pseudo-random mating'. The lesson taught by Li has not been taken on board.

Schizophrenia (SZ) is a severe, complex, and common mental disorder with high heritability (80%), an adult age of onset, and high discordance (∼50%) in monozygotic twins (MZ). Extensive studies on familial and non-familial cases have implicated a number of segregating mutations and de novo changes in SZ that may include changes to the mitochondrial genome. Yet, no single universally causal variant has been identified, highlighting its extensive genetic heterogeneity. This report specifically focuses on the assessment of changes in the mitochondrial genome in a unique set of monozygotic twins discordant (MZD) for SZ using blood. Genomic DNA from six pairs of MZD twins and two sets of parents (N = 16) was hybridized to the Affymetrix Human SNP Array 6.0 to assess mitochondrial DNA copy number (mtDNA-CN). Whole genome sequencing (WGS) and quantitative polymerase chain reaction (qPCR) was performed for a subset of MZD pairs and their parents and was also used to derive mtDNA-CN estimates. The WGS data were further analyzed to generate heteroplasmy (HP) estimates. Our results show that mtDNA-CN estimates for within-pair and mother-child differences were smaller than comparisons involving unrelated individuals, as expected. MZD twins showed discordance in mtDNA-CN estimates and displayed concordance in directionality of differences for mtDNA-CN across all technologies. Further, qPCR performed better than Affymetrix in estimating mtDNA-CN based on relatedness. No reliable differences in HP were detected between MZD twins. The within-MZD differences in mtDNA-CN observed represent postzygotic somatic changes that may contribute to discordance of MZ twins for diseases, including SZ.