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The Journal of Clinical Endocrinology... Dec 2022Clarification of the association among phenotypes, genetic, and environmental factors with clinical laboratory traits can reveal the cause of diseases and assist in...
CONTEXT
Clarification of the association among phenotypes, genetic, and environmental factors with clinical laboratory traits can reveal the cause of diseases and assist in developing methods for the prediction and prevention of diseases. It is difficult to investigate the environmental effect on phenotypes using individual samples because their genetic and environmental factors differ, but we can easily investigate the influence of environmental factors using monozygotic (MZ) twins because they have the same genetic factors.
OBJECTIVE
We aimed to examine the methylation level of CpG sites as an environmental factor affecting adiponectin levels on the basis of the same genetic background using MZ twins and to identify the epigenetic factors related to adiponectin levels and the genetic factors associated with sensitivity to acquired changes in adiponectin.
METHODS
Using 2 groups built from each twin of 232 MZ twin pairs, we performed a replicated epigenome-wide association study to clarify the epigenetic factors affecting adiponectin levels adjusted by genetic risk score. Moreover, we divided twin pairs into concordant and discordant for adiponectin levels. We conducted a genome-wide association study to identify a genetic background specific for discordance.
RESULTS
Methylation levels at 38 CpG sites were reproducibly associated with adjusted adiponectin levels, and some of these CpG sites were in genes related to adiponectin, including CDH13. Some genes related to adiponectin or insulin resistance were found to be genetic factors specific for discordance.
CONCLUSION
We clarified specific epigenetic factors affecting adiponectin levels and genetic factors associated with sensitivity to acquired changes in adiponectin.
Topics: Humans; Adiponectin; DNA Methylation; Genome-Wide Association Study; Twins, Monozygotic; Epigenesis, Genetic
PubMed: 36082629
DOI: 10.1210/clinem/dgac532 -
Acta Odontologica Scandinavica Apr 2022To resolve how the preferred chewing side (PCS) affects facial asymmetry in twins, whether there are differences between monozygotic (MZ) and dizygotic (DZ) twins, and...
OBJECTIVE
To resolve how the preferred chewing side (PCS) affects facial asymmetry in twins, whether there are differences between monozygotic (MZ) and dizygotic (DZ) twins, and whether the twins with PCS have more asymmetric faces compared to symmetrically chewing twins.
MATERIAL AND METHODS
The study included 106 Lithuanian twin pairs of the same sex, 59 MZ and 47 DZ pairs. The data were analysed from facial 3D images and manually added landmarks. 3D images were analysed by Rapidform2006 software and statistical analyses were done by using the R software environment version 4.1.0.
RESULTS
The contralateral effect of PCS and larger chin side was dominant among right and non-right side chewing twins. Being female increased the whole face symmetry.
CONCLUSION
The volume of the chin becomes larger on the side opposite to the twins' habitual chewing side. As the results are quite similar in both twin types, functional factors are more prominent than heredity.
Topics: Face; Facial Asymmetry; Female; Humans; Mastication; Twins, Dizygotic; Twins, Monozygotic
PubMed: 34619067
DOI: 10.1080/00016357.2021.1985166 -
BMC Psychiatry Jun 2023The causes of obsessive-compulsive disorder (OCD) remain unknown. Gene-searching efforts are well underway, but the identification of environmental risk factors is at...
BACKGROUND
The causes of obsessive-compulsive disorder (OCD) remain unknown. Gene-searching efforts are well underway, but the identification of environmental risk factors is at least as important and should be a priority because some of them may be amenable to prevention or early intervention strategies. Genetically informative studies, particularly those employing the discordant monozygotic (MZ) twin design, are ideally suited to study environmental risk factors. This protocol paper describes the study rationale, aims, and methods of OCDTWIN, an open cohort of MZ twin pairs who are discordant for the diagnosis of OCD.
METHODS
OCDTWIN has two broad aims. In Aim 1, we are recruiting MZ twin pairs from across Sweden, conducting thorough clinical assessments, and building a biobank of biological specimens, including blood, saliva, urine, stool, hair, nails, and multimodal brain imaging. A wealth of early life exposures (e.g., perinatal variables, health-related information, psychosocial stressors) are available through linkage with the nationwide registers and the Swedish Twin Registry. Blood spots stored in the Swedish phenylketonuria (PKU) biobank will be available to extract DNA, proteins, and metabolites, providing an invaluable source of biomaterial taken at birth. In Aim 2, we will perform within-pair comparisons of discordant MZ twins, which will allow us to isolate unique environmental risk factors that are in the causal pathway to OCD, while strictly controlling for genetic and early shared environmental influences. To date (May 2023), 43 pairs of twins (21 discordant for OCD) have been recruited.
DISCUSSION
OCDTWIN hopes to generate unique insights into environmental risk factors that are in the causal pathway to OCD, some of which have the potential of being actionable targets.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Brain; Diseases in Twins; Obsessive-Compulsive Disorder; Risk Factors; Twins, Monozygotic; Twin Studies as Topic
PubMed: 37328750
DOI: 10.1186/s12888-023-04897-4 -
Twin Research and Human Genetics : the... Apr 2024Between 2006 and 2021, the Hungarian Twin Registry (HTR) operated a volunteer twin registry of all age groups (50% monozygotic [MZ], 50% dizygotic [DZ], 70% female,...
Between 2006 and 2021, the Hungarian Twin Registry (HTR) operated a volunteer twin registry of all age groups (50% monozygotic [MZ], 50% dizygotic [DZ], 70% female, average age 34 ± 22 years), including 1044 twin pairs, 24 triplets and one quadruplet set. In 2021, the HTR transformed from a volunteer registry into a population-based one, and it was established in the Medical Imaging Centre of Semmelweis University in Budapest. Semmelweis University's innovation fund supported the development of information technology, a phone bank and voicemail infrastructure, administrative materials, and a new website was established where twins and their relatives (parent, foster parent or caregiver) can register. The HTR's biobank was also established: 157,751 individuals with a likely twin-sibling living in Hungary (77,042 twins, 1194 triplets, 20 quadruplets, and one quintuplet) were contacted between February and March of 2021 via sealed letters. Until November 20, 2022, 12,001 twin individuals and their parents or guardians (6724 adult twins, 3009 parents/guardians and 5277 minor twins) registered, mostly online. Based on simple self-reports, 37.6% of the registered adults were MZ twins and 56.8% were DZ; 1.12% were triplets and 4.5% were unidentified. Of the registered children, 22.3% were MZ, 72.7% were DZ, 1.93% were triplets, and 3.05% were unidentified. Of the registered twins, 59.9% were female (including both the adult and minor twins). The registration questionnaire consists of eight parts, including socio-demographic and anthropometric data, smoking habits and medical questions (diseases, operations, therapies). Hungary's twin registry has become the sole and largest population-based twin registry in Central Eastern Europe. This new resource will facilitate performing world-class modern genetic research.
Topics: Humans; Registries; Hungary; Female; Male; Adult; Twins, Dizygotic; Twins, Monozygotic; Child; Middle Aged; Adolescent; Child, Preschool; Aged; Diseases in Twins; Young Adult; Infant
PubMed: 38745426
DOI: 10.1017/thg.2024.15 -
Twin Research and Human Genetics : the... Jun 2022In this study, we analyzed the estimated frequency of monozygotic (MZ) and dizygotic (DZ) spontaneous twins in Lombardy during the period 2007-2017. This is a...
In this study, we analyzed the estimated frequency of monozygotic (MZ) and dizygotic (DZ) spontaneous twins in Lombardy during the period 2007-2017. This is a population-based study using the regional healthcare utilization databases of the Lombardy Region. The total number of spontaneous twin deliveries, in separate strata of like and unlike sex, was obtained. Moreover, estimates of DZ and MZ twin births were calculated using Weinberg's method. The standardized rates (SRs), adjusted for maternal age, of DZ and MZ twin births were computed according to calendar period. The twinning rates were calculated among strata of parity and maternal age. Finally, DZ:MZ ratio was calculated. Among the 734,278 spontaneous deliveries, 9176 (12.5 out of 1000 births) couples of twins were identified. In the three periods considered (i.e. 2007-2010, 2011-2014 and 2015-2017), no trend in the SRs of MZ twins was observed, respectively 0.41 (95% CI [0.40, 0.43]), 0.43 (95% CI [0.42, 0.45]) and 0.43 (95% CI[0.42, 0.45]). Differently, a slightly decreasing trend was observed in DZ twins SRs, respectively 0.87 (95% CI [0.84, 0.89]), 0.81 (95% CI [0.79, 0.83]), and 0.78 (95% CI [0.76, 0.80]). As concerns parity and maternal age, the rate of DZ twin births was consistently higher in nulliparae women aged 35 years or more. In our cohort, despite the increase of maternal age, a decline of spontaneous twin births emerged, especially due to the downward trend of DZ twins.
Topics: Adult; Female; Humans; Maternal Age; Pregnancy; Pregnancy, Twin; Twinning, Dizygotic; Twins, Dizygotic; Twins, Monozygotic
PubMed: 35765814
DOI: 10.1017/thg.2022.19 -
Forensic Science International. Genetics Jan 2021In 2012, a thought experiment in this journal suggested that paternity cases involving monozygotic (MZ) twins as putative fathers could be solved by means of whole... (Review)
Review
In 2012, a thought experiment in this journal suggested that paternity cases involving monozygotic (MZ) twins as putative fathers could be solved by means of whole genome sequencing (WGS). Although arising from a single fertilization event, MZ twins nevertheless continue to acquire somatic mutations during their development, including those that occur in the germline. Provided that paternity had been narrowed down to the twin pair beforehand by classical DNA analysis, one post-zygotic mutation would suffice to assign the paternal compartment of an offspring genome unambiguously to either twin if that mutation is found in the offspring and one twin, but not in the other twin. Since the publication of a proof-of-principle report in 2014, we have worked up five additional cases of MZ twin germline discrimination in real life, four paternity disputes and one criminal case requiring the identification of a sperm trace donor among a pair of MZ twin brothers. In this opinion paper, we report on the experiences made in the course of our work and take a look at possibilities for further development of the approach.
Topics: Embryonic Development; Germ-Line Mutation; Humans; Male; Paternity; Saliva; Spermatozoa; Twins, Monozygotic; Whole Genome Sequencing
PubMed: 33157386
DOI: 10.1016/j.fsigen.2020.102408 -
ELife Aug 2023Smoking-associated DNA methylation levels identified through epigenome-wide association studies (EWASs) are generally ascribed to smoking-reactive mechanisms, but the...
BACKGROUND
Smoking-associated DNA methylation levels identified through epigenome-wide association studies (EWASs) are generally ascribed to smoking-reactive mechanisms, but the contribution of a shared genetic predisposition to smoking and DNA methylation levels is typically not accounted for.
METHODS
We exploited a strong within-family design, that is, the discordant monozygotic twin design, to study reactiveness of DNA methylation in blood cells to smoking and reversibility of methylation patterns upon quitting smoking. Illumina HumanMethylation450 BeadChip data were available for 769 monozygotic twin pairs (mean age = 36 years, range = 18-78, 70% female), including pairs discordant or concordant for current or former smoking.
RESULTS
In pairs discordant for current smoking, 13 differentially methylated CpGs were found between current smoking twins and their genetically identical co-twin who never smoked. Top sites include multiple CpGs in and , which encode subunits of a calcium voltage-gated channel and G protein, respectively. These proteins interact with the nicotinic acetylcholine receptor, suggesting that methylation levels at these CpGs might be reactive to nicotine exposure. All 13 CpGs have been previously associated with smoking in unrelated individuals and data from monozygotic pairs discordant for former smoking indicated that methylation patterns are to a large extent reversible upon smoking cessation. We further showed that differences in smoking level exposure for monozygotic twins who are both current smokers but differ in the number of cigarettes they smoke are reflected in their DNA methylation profiles.
CONCLUSIONS
In conclusion, by analysing data from monozygotic twins, we robustly demonstrate that DNA methylation level in human blood cells is reactive to cigarette smoking.
FUNDING
We acknowledge funding from the National Institute on Drug Abuse grant DA049867, the Netherlands Organization for Scientific Research (NWO): Biobanking and Biomolecular Research Infrastructure (BBMRI-NL, NWO 184.033.111) and the BBRMI-NL-financed BIOS Consortium (NWO 184.021.007), NWO Large Scale infrastructures X-Omics (184.034.019), Genotype/phenotype database for behaviour genetic and genetic epidemiological studies (ZonMw Middelgroot 911-09-032); Netherlands Twin Registry Repository: researching the interplay between genome and environment (NWO-Groot 480-15-001/674); the Avera Institute, Sioux Falls (USA), and the National Institutes of Health (NIH R01 HD042157-01A1, MH081802, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995); epigenetic data were generated at the Human Genomics Facility (HuGe-F) at ErasmusMC Rotterdam. Cotinine assaying was sponsored by the Neuroscience Campus Amsterdam. DIB acknowledges the Royal Netherlands Academy of Science Professor Award (PAH/6635).
Topics: United States; Female; Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Male; Twins, Monozygotic; DNA Methylation; Biological Specimen Banks; Smoking; Epigenome
PubMed: 37643467
DOI: 10.7554/eLife.83286 -
Genome Biology Jan 2018Monozygotic twins have long been studied to estimate heritability and explore epigenetic influences on phenotypic variation. The phenotypic and epigenetic similarities...
BACKGROUND
Monozygotic twins have long been studied to estimate heritability and explore epigenetic influences on phenotypic variation. The phenotypic and epigenetic similarities of monozygotic twins have been assumed to be largely due to their genetic identity.
RESULTS
Here, by analyzing data from a genome-scale study of DNA methylation in monozygotic and dizygotic twins, we identified genomic regions at which the epigenetic similarity of monozygotic twins is substantially greater than can be explained by their genetic identity. This "epigenetic supersimilarity" apparently results from locus-specific establishment of epigenotype prior to embryo cleavage during twinning. Epigenetically supersimilar loci exhibit systemic interindividual epigenetic variation and plasticity to periconceptional environment and are enriched in sub-telomeric regions. In case-control studies nested in a prospective cohort, blood DNA methylation at these loci years before diagnosis is associated with risk of developing several types of cancer.
CONCLUSIONS
These results establish a link between early embryonic epigenetic development and adult disease. More broadly, epigenetic supersimilarity is a previously unrecognized phenomenon that may contribute to the phenotypic similarity of monozygotic twins.
Topics: CpG Islands; DNA; DNA Methylation; Epigenesis, Genetic; Genome, Human; Humans; Models, Genetic; Neoplasms; Twins, Dizygotic; Twins, Monozygotic
PubMed: 29310692
DOI: 10.1186/s13059-017-1374-0 -
The Journal of Clinical Pediatric... Nov 2021The 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: 34740261
DOI: 10.17796/1053-4625-45.5.12 -
Brain and Cognition Dec 2023Hyperlexia, a strong orientation towards written materials, along with a discrepancy between the precocious acquisition of decoding skills and weaker comprehension...
BACKGROUND
Hyperlexia, a strong orientation towards written materials, along with a discrepancy between the precocious acquisition of decoding skills and weaker comprehension abilities, characterizes up to 20% of autistic children. Sometimes perceived as an obstacle to oral language acquisition, hyperlexia may alternatively be the first step in a non-social pathway of language acquisition in autism.
METHOD
We describe two monozygotic twin brothers, both autistic and hyperlexic, from the ages of 4 to 8 years old. Following an in-depth diagnostic assessment, we investigated cross-sectionally and longitudinally their verbal and non-verbal cognitive abilities, language, reading and writing skills, interests, and strengths.
RESULTS
The twins' features, including their high non-verbal level of intelligence, their special interests, and their skills in various domains, were highly similar. Their language consisted exclusively of letters and numbers until their fourth year. After that, their vocabulary broadened until they developed full sentences, and their perception-related interests expanded and merged over time to serve the development of other skills.
CONCLUSION
Our results show that hyperlexic skills can be harnessed to favor oral language development. Given the strong concordance between the twins' cognitive and behavioral phenotypes, we discuss the environmental and genetic influence that could explain their abilities.
Topics: Child; Child, Preschool; Humans; Male; Autistic Disorder; Language Development; Longitudinal Studies; Reading; Twins, Monozygotic
PubMed: 37839243
DOI: 10.1016/j.bandc.2023.106099