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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 -
The New England Journal of Medicine Aug 2020
Topics: Female; Heart Rate, Fetal; Humans; Pregnancy; Pregnancy, Twin; Twins, Monozygotic; Umbilical Cord
PubMed: 32786191
DOI: 10.1056/NEJMicm1916811 -
Human Brain Mapping Nov 2021Perceptions of spiteful behavior are common, distinct from rational fear, and may undergird persecutory ideation. To test this hypothesis and investigate neural...
Perceptions of spiteful behavior are common, distinct from rational fear, and may undergird persecutory ideation. To test this hypothesis and investigate neural mechanisms of persecutory ideation, we employed a novel economic social decision-making task, the Minnesota Trust Game (MTG), during neuroimaging in patients with schizophrenia (n = 30) and community monozygotic (MZ) twins (n = 38; 19 pairs). We examined distinct forms of mistrust, task-related brain activation and connectivity, and investigated relationships with persecutory ideation. We tested whether co-twin discordance on these measurements was correlated to reflect a common source of underlying variance. Across samples persecutory ideation was associated with reduced trust only during the suspiciousness condition, which assessed spite sensitivity given partners had no monetary incentive to betray. Task-based activation contrasts for specific forms of mistrust were limited and unrelated to persecutory ideation. However, task-based connectivity contrasts revealed a dorsal cingulate anterior insula network sensitive to suspicious mistrust, a left frontal-parietal (lF-P) network sensitive to rational mistrust, and a ventral medial/orbital prefrontal (vmPFC/OFC) network that was sensitive to the difference between these forms of mistrust (all p < .005). Higher persecutory ideation was predicted only by reduced connectivity between the vmPFC/OFC and lF-P networks (p = .005), which was only observed when the intentions of the other player were relevant. Moreover, co-twin differences in persecutory ideation predicted co-twin differences in both spite sensitivity and in vmPFC/OFC-lF-P connectivity. This work found that interconnectivity may be particularly important to the complex neurobiology underlying persecutory ideation, and that unique environmental variance causally linked persecutory ideation, decision-making, and brain connectivity.
Topics: Adolescent; Adult; Cerebral Cortex; Connectome; Decision Making; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Schizophrenia; Social Perception; Trust; Twins, Monozygotic; Young Adult
PubMed: 34331484
DOI: 10.1002/hbm.25613 -
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 -
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 -
Twin Research and Human Genetics : the... Dec 2019The Louisville Twin Study (LTS) is nationally recognized as one of the largest and most comprehensive studies of child development related to multiple birth status. The... (Review)
Review
The Louisville Twin Study (LTS) is nationally recognized as one of the largest and most comprehensive studies of child development related to multiple birth status. The LTS is unique because of the extensive longitudinal face-to-face assessments, the frequency of data collection, the inclusion of data on additional family members (i.e., parents, siblings, grandparents; and later, twins' own spouses and children), and the variety of data collection methods used. Data preservation efforts began in 2008 and are largely complete, although efforts are ongoing to obtain funding to convert the electronic data to a newer format. A pilot study was completed in the summer of 2018 to bring the twins, who are now middle-aged, back for testing. A grant is currently under review to extend the pilot study to include all former participants who are now ≥40 years of age. Opportunities for collaboration are welcome.
Topics: Adult; Child; Child Development; Family; Female; History, 20th Century; History, 21st Century; Humans; Longitudinal Studies; Male; Pilot Projects; Registries; Twin Studies as Topic; Twins, Monozygotic
PubMed: 31362801
DOI: 10.1017/thg.2019.37 -
Digestive Diseases and Sciences Jun 2022Twin studies have long been used to infer heritability. Within the 'omics era, twin cohorts have even greater research potential. This study describes the formation of...
BACKGROUND AND AIMS
Twin studies have long been used to infer heritability. Within the 'omics era, twin cohorts have even greater research potential. This study describes the formation of the UK IBD Twin Registry and analysis of concordance and environmental factors.
METHOD
Twin pairs with IBD were recruited by advertising via IBD charities and social media, re-tracing a dormant IBD database and clinician referral. Details of zygosity, concordance, disease history and environmental factors were assessed. Pair concordance was calculated, and environmental factors were analysed with logistic regression models adjusted for zygosity and concordance.
RESULTS
Ninety-one twin pairs were included in the analysis; forty-two with CD and forty-nine with UC. More MZ twin pairs with CD were concordant compared with DZ pairs, thus inferring heritability (Chi-sq. 15.6. P < 0.001). In UC, MZ concordance was also numerically greater. Cigarette smoking was predictive of CD (OR 2.66, 95% CI 1.16 to 6.07 P = 0.02); there may be an independent association with cannabis smoking (OR 2.59 95% CI 0.89 to 7.55 P = 0.08). Breastfeeding was protective against UC (OR 0.48, 95% CI 0.25-0.93, P = 0.03), but not CD. Self-reports of less occurrences of gastroenteritis than peers were protective against future UC onset (OR 0.33 95% CI 0.15 to 0.74, P = 0.01). Method of delivery, parental attitudes towards hygiene and recall of diet did not impact future IBD concordance.
CONCLUSIONS
This study supports the heritability of IBD. Twin study analysis was able to elucidate environmental factors associated with IBD.
Topics: Diseases in Twins; Humans; Inflammatory Bowel Diseases; Registries; Risk Factors; Twins, Dizygotic; Twins, Monozygotic; United Kingdom
PubMed: 34097167
DOI: 10.1007/s10620-021-07080-5 -
Ultrasound in Obstetrics & Gynecology :... Oct 2022
Topics: Female; Fetofetal Transfusion; Humans; Placenta; Pregnancy; Twins, Monozygotic
PubMed: 35304934
DOI: 10.1002/uog.24899 -
Frontiers in Cellular and Infection... 2021The objectives are to estimate the vertical transmission rate in twins relative to singleton pregnancies, to evaluate whether discordance within twin pairs is rare, and...
OBJECTIVE
The objectives are to estimate the vertical transmission rate in twins relative to singleton pregnancies, to evaluate whether discordance within twin pairs is rare, and to characterize concordance within monozygotic and dizygotic twin pairs in relation to hereditability.
METHODS
We first sought to estimate the vertical transmission rate of congenital CMV infection in twins by gathering cohort-based studies of congenital CMV in which vertical transmission in both singleton and twin pregnancies was reported. This also allowed us to compare singleton and twin infection rates. From the above studies and other large cohorts of congenitally infected infants, the percentage of discordantly infected twin pairs determined whether this is a rare phenomenon. Theorizing discordance is not rare, we then analyzed data from cases with twin outcomes for congenital CMV infection, according to whether the twins were monozygotic or dizygotic, and calculated their corresponding concordance rates to estimate the broad-sense heritability. Lastly, we described other factors that might affect vertical transmission.
RESULTS
From five articles following at-risk pregnancies, the rate of vertical transmission in twin pregnancies is 58.7% (95% CI 43.3-72.3%) whereas in singleton pregnancies it is 31.4% (95% CI: 29.0-34.0%) = 0.0002. Of ten studies of larger cohorts of infants with congenital CMV infection, 21 of 42 twin pairs with at least one twin infected were discordant for congenital CMV (50.0%, 95% CI: 34.4-65.6%) indicating discordance of congenital CMV infection in twin pairs is not rare. Of 28 studies covering 37 twin pairs where at least one twin had congenital CMV, and zygosity was known, eleven of thirteen monozygotic twin pairs (84.6%; 95% CI: 53.7-97.3%) were concordant for CMV infection, and nine of twenty-four dizygotic twin pairs (37.5%; 95% CI: 19.6-59.2%) were concordant for infection giving an estimated hereditability of 94.2%. Within these 37 twin pairs, factors such as primary or recurrent maternal infection, prematurity, growth discordance, and sex are described; however, in many of these cases these factors are unknown.
CONCLUSION
The rate of vertical transmission of congenital CMV is higher for twins than singletons. Discordance of congenital CMV in twins is not rare and suggests a possible genetic susceptibility to congenital CMV.
Topics: Cytomegalovirus; Diseases in Twins; Female; Humans; Pregnancy; Pregnancy, Twin; Twins, Dizygotic; Twins, Monozygotic
PubMed: 34350131
DOI: 10.3389/fcimb.2021.676988