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Genome Biology Dec 2023Recent state-of-the-art sequencing technologies enable the investigation of challenging regions in the human genome and expand the scope of variant benchmarking...
BACKGROUND
Recent state-of-the-art sequencing technologies enable the investigation of challenging regions in the human genome and expand the scope of variant benchmarking datasets. Herein, we sequence a Chinese Quartet, comprising two monozygotic twin daughters and their biological parents, using four short and long sequencing platforms (Illumina, BGI, PacBio, and Oxford Nanopore Technology).
RESULTS
The long reads from the monozygotic twin daughters are phased into paternal and maternal haplotypes using the parent-child genetic map and for each haplotype. We also use long reads to generate haplotype-resolved whole-genome assemblies with completeness and continuity exceeding that of GRCh38. Using this Quartet, we comprehensively catalogue the human variant landscape, generating a dataset of 3,962,453 SNVs, 886,648 indels (< 50 bp), 9726 large deletions (≥ 50 bp), 15,600 large insertions (≥ 50 bp), 40 inversions, 31 complex structural variants, and 68 de novo mutations which are shared between the monozygotic twin daughters. Variants underrepresented in previous benchmarks owing to their complexity-including those located at long repeat regions, complex structural variants, and de novo mutations-are systematically examined in this study.
CONCLUSIONS
In summary, this study provides high-quality haplotype-resolved assemblies and a comprehensive set of benchmarking resources for two Chinese monozygotic twin samples which, relative to existing benchmarks, offers expanded genomic coverage and insight into complex variant categories.
Topics: Humans; Benchmarking; East Asian People; Genomics; Haplotypes; High-Throughput Nucleotide Sequencing; Sequence Analysis, DNA; Twins, Monozygotic; Twin Studies as Topic
PubMed: 38049885
DOI: 10.1186/s13059-023-03116-3 -
Journal of Neurology, Neurosurgery, and... Oct 2007In monozygotic twin pairs with Alzheimer's disease, a high concordance of neuritic plaque and tangle pathology was found but differences in age of onset, duration of...
In monozygotic twin pairs with Alzheimer's disease, a high concordance of neuritic plaque and tangle pathology was found but differences in age of onset, duration of disease, apo E status and development of symptoms in the course of the disease
Topics: Age of Onset; Alzheimer Disease; Apolipoproteins E; Humans; Neurofibrillary Tangles; Plaque, Amyloid; Twin Studies as Topic; Twins, Monozygotic
PubMed: 17878189
DOI: 10.1136/jnnp.2007.118562 -
Fertility and Sterility Oct 2015To estimate the relative contribution of genetic influences and prevalence on endometriosis.
OBJECTIVE
To estimate the relative contribution of genetic influences and prevalence on endometriosis.
DESIGN
Analysis of self-reported data from a nationwide population-based twin registry.
SETTING
Not applicable.
PATIENT(S)
A total of 28,370 women, female monozygotic (MZ) or dizygotic (DZ) twins, who participated in either of two surveys (1998-2002 or 2005-2006).
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
Self-reported endometriosis, validated by medical records.
RESULT(S)
A history of endometriosis was reported by 1,228 female twins. The probandwise concordance was 0.21 for MZ and 0.10 for DZ twins. Higher within-pair (tetrachoric) correlation was observed among MZ (0.47) compared with DZ (0.20) twins. The best-fitting model revealed a contribution of 47% by additive genetic factors and the remaining 53% attributed to unique environmental effects.
CONCLUSION(S)
Our findings suggest both genetic and unique (nonshared) environmental influences on the complex etiology of endometriosis and support the hypothesis that genes have a strong influence on phenotypic manifestations of endometriosis.
Topics: Adult; Aged; Cross-Sectional Studies; Diseases in Twins; Endometriosis; Female; Genetic Predisposition to Disease; Humans; Middle Aged; Models, Genetic; Quantitative Trait, Heritable; Twins, Dizygotic; Twins, Monozygotic; Young Adult
PubMed: 26209831
DOI: 10.1016/j.fertnstert.2015.06.035 -
Genes Feb 2019Studies with twins provide fundamental insights to lifespans of humans. We aim to clarify if monozygotic and dizygotic twin individuals differ in lifespan, that is, if...
Studies with twins provide fundamental insights to lifespans of humans. We aim to clarify if monozygotic and dizygotic twin individuals differ in lifespan, that is, if zygosity matters. We investigate whether a possible difference in mortality after infancy between zygosities is stable in different age cohorts, and whether the difference remains when twins with unknown zygosity are taken into account. Further, we compare the distribution of long-livers, that is, the upper-tail of the lifespan distribution, between monozygotic and same-sex dizygotic twin individuals. The Danish Twin Registry provides a nationwide cohort of 109,303 twins born during 1870 to 1990 with valid vital status. Standard survival analysis is used to compare mortality in monozygotic and dizygotic twin individuals and twin individuals with unknown zygosity. The mortality of monozygotic and dizygotic twin individuals differs slightly after taking into consideration effects of birth- and age-cohorts, gender differences, and that twins are paired. However, no substantial nor systematic differences remain when taking twins with unknown zygosity into account. Further, the distribution of long-livers is very similar by zygosity, suggesting the same mortality process. The population-based and oldest twin cohort ever studied suggests that monozygotic and dizygotic twins have similar lifespans.
Topics: Adult; Aged; Denmark; Female; Humans; Longevity; Male; Middle Aged; Mortality; Registries; Twins, Dizygotic; Twins, Monozygotic
PubMed: 30791679
DOI: 10.3390/genes10020166 -
Developmental Science Nov 2018School performance is one of the most stable and heritable psychological characteristics. Notwithstanding, monozygotic twins (MZ), who have identical genotypes, differ...
School performance is one of the most stable and heritable psychological characteristics. Notwithstanding, monozygotic twins (MZ), who have identical genotypes, differ in school performance. These MZ differences result from non-shared environments that do not contribute to the similarity within twin pairs. Because to date few non-shared environmental factors have been reliably associated with MZ differences in school performance, they are thought to be idiosyncratic and due to chance, suggesting that the effect of non-shared environments on MZ differences are age- and trait-specific. In a sample of 2768 MZ twin pairs, we found first that MZ differences in school performance were moderately stable from age 12 through 16, with differences at the ages 12 and 14 accounting for 20% of the variance in MZ differences at age 16. Second, MZ differences in school performance correlated positively with MZ differences across 16 learning-related variables, including measures of intelligence, personality and school attitudes, with the twin who scored higher on one also scoring higher on the other measures. Finally, MZ differences in the 16 learning-related variables accounted for 22% of the variance in MZ differences in school performance at age 16. These findings suggest that, unlike for other psychological domains, non-shared environmental factors affect school performance in systematic ways that have long-term and generalist influence. Our findings should motivate the search for non-shared environmental factors responsible for the stable and systematic effects on children's differences in school performance. A video abstract of this article can be viewed at: https://youtu.be/0bw2Fl_HGq0.
Topics: Academic Performance; Adolescent; Attitude; Child; Gene-Environment Interaction; Humans; Individuality; Intelligence; Personality; Twins, Monozygotic
PubMed: 29920866
DOI: 10.1111/desc.12694 -
Aging May 2021We investigated whether lifestyle influences epigenetic aging in 143 monozygotic twin pairs discordant for the combined healthy lifestyle score. Twins were scored for...
We investigated whether lifestyle influences epigenetic aging in 143 monozygotic twin pairs discordant for the combined healthy lifestyle score. Twins were scored for four lifestyle factors as unhealthy or healthy; non-smoker, moderate drinker, adequate fruit and vegetable intake, and sufficient physical activity. The combined healthy lifestyle score was calculated for each participant by summing the binary score for each factor. Individual and co-twin analyses were used to assess the relationship between single or combined lifestyle scores, along with DNA methylation age acceleration (AA) calculated using Horvath's and Li's epigenetic clocks, focusing on AA and intrinsic epigenetic age acceleration (IEAA) measures. Compared with the twins that scored no or one healthy lifestyle point, those who scored four healthy lifestyle points had lower Li_IEAA with similar results observed in the co-twin analysis. No significant relationships were found in analyses based on Horvath's clock, although the direction of correlations was consistent with that determined using Li's clock. Smoking and drinking did not significantly affect DNA methylation AA; however, physical activity and intake of vegetables and fruits did, although the influence varied depending on the epigenetic clock. Our findings suggest that a healthy lifestyle may be an important way to delay aging and prevent age-related diseases.
Topics: Aging; Alcohol Drinking; DNA Methylation; Epigenesis, Genetic; Exercise; Female; Fruit; Healthy Lifestyle; Humans; Male; Middle Aged; Risk Factors; Smoking; Twins, Monozygotic; Vegetables
PubMed: 34032609
DOI: 10.18632/aging.203022 -
Social Psychiatry and Psychiatric... Oct 2015Consistent and non-specific associations have been found between parenting style and major depression, anxiety disorders, and externalizing behavior. Although often...
PURPOSE
Consistent and non-specific associations have been found between parenting style and major depression, anxiety disorders, and externalizing behavior. Although often considered part of twins' shared environment, parenting can also be conceptualized as non-shared environment. Non-shared environmental influences have important effects on development but are difficult to test and sort out because of the possible confounding effects of gene-environment interactions and evocative gene-environment correlations. The monozygotic (MZ) differences approach is one way to analytically investigate non-shared environment.
METHODS
The aim of the present study is to use the MZ differences approach to investigate the relationship between differential parenting among 1303 twin pairs (mean age 36.69 ± 8.56) and differences in total symptom counts of major depression (MD), generalized anxiety disorder (GAD), conduct disorder (CD), and anti-social behavior (ASB) during adulthood.
RESULTS
Although effect sizes tended to be small, a number of results were significantly different from zero. Perceived differences in parental coldness was positively associated with internalizing disorders. Differences in protectiveness were negatively associated with MD, GAD, and ASB. Differences in authoritarianism were positively associated with MD and CD, but negatively associated with ASB.
CONCLUSIONS
Perceived differences in parenting style are associated with differences in MD, GAD, CD, and ASB outcomes in a sample of MZ twins. Despite the lack of a basis for making causal inferences about parenting style and psychopathology, these results are suggestive of such a relationship and show that non-shared environmental influence of parenting does in some cases significantly predict adult psychopathology.
Topics: Adult; Anxiety Disorders; Authoritarianism; Conduct Disorder; Depressive Disorder, Major; Diseases in Twins; Female; Humans; Longitudinal Studies; Male; Parenting; Parents; Psychopathology; Risk; Social Behavior Disorders; Social Environment; Twins, Monozygotic
PubMed: 25940788
DOI: 10.1007/s00127-015-1065-7 -
The Journal of Clinical Pediatric... Mar 2022The aim of this study is to investigate the relative contributions of genetic and environmental factors to variations in dental dimensions in a sample of Turkish twins,...
BACKGROUND
The aim of this study is to investigate the relative contributions of genetic and environmental factors to variations in dental dimensions in a sample of Turkish twins, and to estimate heritability using dental casts.
STUDY DESIGN
The study samples were selected from the twin children between 3-15 years old who referred for their first dental examination. Fifty nine monozygotic and one hundred and forty three dizygotic twin pairs were examined in the study. The alginate impression material used to create the plaster model of maxilla and mandible. Anterior arch width, posterior arch width, arch length and arch circumference were measured on models prepared from measurements taken for both maxilla and mandible with digital caliper. The similarities and differences of the measurements were compared between pairs of twins and zygocytes. Morever, the effects of bad oral habits, bruxism, a result of psychosocial factors on measurements were examined. Statistical analysis was performed using Paired T Test, Wilcoxon Test and Mann Whitney U test.
RESULTS
A total of 404 dental models of 118 (29.2%) monozygotic and 286 (70.8%) dizygotic twins were evaluated. There was no statistical difference between sibling pairs in both monozygotic and dizygotic twins. The measurement similarity between twin siblings differed according to zygosity in all measurements (p<0.05). It has been observed that the finger sucking and mouth breathing affect the dental arch measurements (p<0.05).
CONCLUSION
These results indicate that the differences in dental arch dimensions between monozygotic twin pairs are less than the difference between dizygotic twin pairs.
Topics: Adolescent; Child; Child, Preschool; Dental Arch; Humans; Mandible; Maxilla; Twins, Dizygotic; Twins, Monozygotic
PubMed: 35533222
DOI: 10.17796/1053-4625-46.2.12 -
BMC Medicine Aug 2012Genetic-epidemiological studies on monozygotic (MZ) twins have been used for decades to tease out the relative contributions of genes and the environment to a trait.... (Review)
Review
Genetic-epidemiological studies on monozygotic (MZ) twins have been used for decades to tease out the relative contributions of genes and the environment to a trait. Phenotypic discordance in MZ twins has traditionally been ascribed to non-shared environmental factors acting after birth, however recent data indicate that this explanation is far too simple. In this paper, we review other reasons for discordance, including differences in the in utero environment, genetic mosaicism, and stochastic factors, focusing particularly on epigenetic discordance. Epigenetic differences are gaining increasing recognition. Although it is clear that in specific cases epigenetic alterations provide a causal factor in disease etiology, the overall significance of epigenetics in twin discordance remains unclear. It is also challenging to determine the causality and relative contributions of environmental, genetic, and stochastic factors to epigenetic variability. Epigenomic profiling studies have recently shed more light on the dynamics of temporal methylation change and methylome heritability, yet have not given a definite answer regarding their relevance to disease, because of limitations in establishing causality. Here, we explore the subject of epigenetics as another component in human phenotypic variability and its links to disease focusing particularly on evidence from MZ twin studies.
Topics: DNA Methylation; Diseases in Twins; Epigenesis, Genetic; Fetus; Gene-Environment Interaction; Humans; Stochastic Processes; Twins, Monozygotic
PubMed: 22898292
DOI: 10.1186/1741-7015-10-93 -
Behavior Genetics Jul 2020The characterizing features of autism spectrum disorder (ASD) are continuously distributed in nature; however, prior twin studies have not systematically incorporated...
The characterizing features of autism spectrum disorder (ASD) are continuously distributed in nature; however, prior twin studies have not systematically incorporated this knowledge into estimations of concordance and discordance. We conducted a quantitative analysis of twin-twin similarity for autistic trait severity in three existing data sets involving 366 pairs of uniformly-phenotyped monozygotic (MZ) twins with and without ASD. Probandwise concordance for ASD was 96%; however, MZ trait correlations differed markedly for pairs with ASD trait burden below versus above the threshold for clinical diagnosis, with Rs on the order of 0.6 versus 0.1, respectively. Categorical MZ twin discordance for ASD diagnosis is rare and more appropriately operationalized by standardized quantification of twin-twin differences. Here we provide new evidence that although ASD itself is highly heritable, variation-in-severity of symptomatology above the diagnostic threshold is substantially influenced, in contrast, by non-shared environmental factors which may identify novel targets of early ASD amelioration.
Topics: Adolescent; Autism Spectrum Disorder; Autistic Disorder; Child; Child, Preschool; Databases, Factual; Databases, Genetic; Diseases in Twins; Female; Gene-Environment Interaction; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Male; Phenotype; Twins, Dizygotic; Twins, Monozygotic
PubMed: 31853901
DOI: 10.1007/s10519-019-09987-2