monozygotic twin
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2022 ◽  
Author(s):  
Jay Joseph

In 1990, Thomas J. Bouchard, Jr. and colleagues published the widely cited 1990 “Minnesota Study of Twins Reared Apart” (MISTRA) Science IQ study. To arrive at the conclusion that “IQ is strongly affected by genetic factors,” Bouchard and colleagues omitted their control group reared-apart dizygotic twin (“DZA”) IQ-score correlations. Near-full-sample correlations published after the study’s 2000 endpoint show that the reared-apart monozygotic twin (“MZA”) and DZA group IQ correlations did not differ at a statistically significant level, suggesting that the study failed the first step in determining that IQ scores are influenced by heredity. After bypassing the model-fitting technique they used in most non-IQ MISTRA studies, the researchers assumed that the MZA group IQ-score correlation alone “directly estimates heritability.” This method was based on unsupported assumptions by the researchers, and they largely overlooked the confounding influence of cohort effects. Bouchard and colleagues then decided to count most environmental influences they did recognize as genetic influences. I conclude that the MISTRA IQ study failed to discover genetic influences on IQ scores and cognitive ability across the studied population, and that the study should be evaluated in the context of psychology’s replication problem.


2022 ◽  
Vol 12 ◽  
Author(s):  
Hanna Huuki ◽  
Seppo Ahvenjärvi ◽  
Paula Lidauer ◽  
Milka Popova ◽  
Johanna Vilkki ◽  
...  

The development of the functional rumen in calves involves a complex interplay between the host and host-related microbiome. Attempts to modulate rumen microbial community establishment may therefore have an impact on weaning success, calf health, and animal performance later in life. In this experiment, we aimed to elucidate how rumen liquid inoculum from an adult cow, provided to calves during the pre-weaning period, influences the establishment of rumen bacterial, archaeal, fungal, and ciliate protozoan communities in monozygotic twin calves (n = 6 pairs). The calves were divided into treatment (T-group) and control (C-group) groups, where the T-group received fresh rumen liquid as an oral inoculum during a 2–8-week period. The C-group was not inoculated. The rumen microbial community composition was determined using bacterial and archaeal 16S ribosomal RNA (rRNA) gene, protozoal 18S rRNA gene, and fungal ITS1 region amplicon sequencing. Animal weight gain and feed intake were monitored throughout the experiment. The T-group tended to have a higher concentrate intake (Treatment: p < 0.08) and had a significantly higher weekly weight gain (Treatment: p < 0.05), but no significant difference in volatile fatty acid concentrations between the groups was observed. In the T-group, the inoculum stimulated the earlier establishment of mature rumen-related bacterial taxa, affecting significant differences between the groups until 6 weeks of age. The inoculum also increased the archaeal operational taxonomic unit (OTU) diversity (Treatment: p < 0.05) but did not affect the archaeal quantity. Archaeal communities differed significantly between groups until week 4 (p = 0.02). Due to the inoculum, ciliate protozoa were detected in the T-group in week 2, while the C-group remained defaunated until 6 weeks of age. In week 8, Eremoplastron dilobum was the dominant ciliate protozoa in the C-group and Isotricha sp. in the T-group, respectively. The Shannon diversity of rumen anaerobic fungi reduced with age (Week: p < 0.01), and community establishment was influenced by a change of diet and potential interaction with other rumen microorganisms. Our results indicate that an adult cow rumen liquid inoculum enhanced the maturation of bacterial and archaeal communities in pre-weaning calves’ rumen, whereas its effect on eukaryotic communities was less clear and requires further investigation.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
C. Iranzo-Tatay ◽  
D. Hervas-Marin ◽  
L. M. Rojo-Bofill ◽  
D. Garcia ◽  
F. J. Vaz-Leal ◽  
...  

AbstractUp until now, no study has looked specifically at epigenomic landscapes throughout twin samples, discordant for Anorexia nervosa (AN). Our goal was to find evidence to confirm the hypothesis that epigenetic variations play a key role in the aetiology of AN. In this study, we quantified genome-wide patterns of DNA methylation using the Infinium Human DNA Methylation EPIC BeadChip array (“850 K”) in DNA samples isolated from whole blood collected from a group of 7 monozygotic twin pairs discordant for AN. Results were then validated performing a genome-wide DNA methylation profiling using DNA extracted from whole blood of a group of non-family-related AN patients and a group of healthy controls. Our first analysis using the twin sample revealed 9 CpGs associated to a gene. The validation analysis showed two statistically significant CpGs with the rank regression method related to two genes associated to metabolic traits, PPP2R2C and CHST1. When doing beta regression, 6 of them showed statistically significant differences, including 3 CpGs associated to genes JAM3, UBAP2L and SYNJ2. Finally, the overall pattern of results shows genetic links to phenotypes which the literature has constantly related to AN, including metabolic and psychological traits. The genes PPP2R2C and CHST1 have both been linked to the metabolic traits type 2 diabetes through GWAS studies. The genes UBAP2L and SYNJ2 have been related to other psychiatric comorbidity.


Author(s):  
Benedicte Bang ◽  
Jesper Eisfeldt ◽  
Gisela Barbany ◽  
Arja Harila-Saari ◽  
Mats Heyman ◽  
...  

Genetic analysis of leukemic clones in monozygotic twins with concordant ALL has proved a unique opportunity to gain insight into the molecular phylogenetics of leukemogenesis. Using whole genome sequencing, we characterized constitutional and somatic SNVs/indels and structural variants in a monozygotic twin pair with concordant ETV6-RUNX1 positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In addition, digital PCR (dPCR) was applied to evaluate the presence of and quantify selected somatic variants at birth, diagnosis and remission. A shared somatic complex rearrangement involving chromosomes 11, 12 and 21 with identical fusion sequences in leukemias of both twins offered direct proof of a common clonal origin. The ETV6-RUNX1 fusion detected at diagnosis was found to originate from this complex rearrangement. A shared somatic frameshift deletion in UBA2 was also identified in diagnostic samples. In addition, each leukemia independently acquired analogous deletions of three genes recurrently targeted in BCP-ALLs (ETV6, ATF7IP and RAG1/RAG2) providing evidence of a convergent clonal evolution, only explained by a strong concurrent selective pressure. Quantification of the UBA2 deletion by dPCR surprisingly indicated it persisted in remission. This, for the first time to our knowledge, provided evidence of a UBA2 variant preceding the well-established initiating event ETV6-RUNX1. Further, we suggest the UBA2 deletion exerted a leukemia predisposing effect and that its essential role in SUMOylation, regulating nearly all physiological and pathological cellular processes such as DNA-repair by non-homologous end joining, may hold a mechanistic explanation for the predisposition.


2021 ◽  
Author(s):  
Marie-Louise Kullberg ◽  
Charlotte C van Schie ◽  
Andrea Allegrini ◽  
Yasmin Iona Ahmadzadeh ◽  
Daniel Wechsler ◽  
...  

Objective. To elucidate associations between parental harsh discipline and child emotional and behavioural problems in monozygotic twins aged 9, 12 and 16 and to compare distinct approaches to causal inference.Method. Child reports of 5,698 identical twins from the Twins Early Development Study (TEDS) were analysed. We tested three types of longitudinal structural equation models: a cross-lagged panel model (CLPM), a random intercept CLPM (RI-CLPM) and a monozygotic twin difference version of the CLPM (MZD-CLPM). Results. Given the study aim to infer causation, interpretation of models focussed primarily on the magnitude and significance of cross-lagged associations. Behavioural problems resulted in harsher parental discipline across all models. In the CLPM, we found bidirectional effects between parental discipline behavioural problems at age 9 and 12. Point estimates of all other associations between parental harsh discipline and child emotional and behavioural problems were in the same direction but magnitude varied across models. In the MZD-CLPM, twin differences in harsh parental discipline at 9 predicted twin differences in emotional problems at 12. In the RI-CLPM, emotional problems at 12 predicted a reduction in harsh parental discipline at 16 within person. Conclusions. Findings can be interpreted as corroborating (but not definite) evidence in favour of a causal effect of child behavioural problems on later experienced harsh parental discipline. Yet, in light of the triangulated methods, results also illustrate divergence in the MZD-CLPM and RI-CLPM outcomes, and underline the importance of a well-defined research question, careful model selection and refining causal conclusions on within-person processes.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 756-756
Author(s):  
Elizabeth Teas ◽  
Olivia Robertson ◽  
Kristine Marceau ◽  
Elliot Friedman

Abstract Prior research on the causality and directionality between disease and functional limitations is ambiguous. The current study used longitudinal monozygotic twin data to test both directions linking disease burden and functional limitations in middle-aged and older adults, controlling for genetic and familial factors. We also examined potential moderation by psychological well-being. The Twins sub-sample from the first two waves of the longitudinal Midlife in the United States (MIDUS) study was used (Wave 1: 1995-1996, Wave 2: 2004-2006). Only monozygotic twins (N = 713) were included in analyses. In separate multi-level models, we examined disease burden at MIDUS 2 predicted by functional limitations at MIDUS 1 and MIDUS 2 functional limitations predicted by disease burden at MIDUS 1. Disease burden and functional limitations at MIDUS 2 varied substantially within families. There was no within-family association of earlier functional limitations with change in later disease burden (b = .40, p = .39), but there was a within-family association such that the twin with higher baseline disease burden had a greater increase in functional limitations than his/her co-twin (b = .06, p = .02). Well-being was not a moderator in either model. We found support for a potentially causal association between earlier disease burden and later increases in functional limitations, consistent with the Disablement Process Model. Sensitivity analyses confirm the detected within-family effect. Possible mechanisms linking disease burden and functional limitations are discussed as potential targets for future research.


Author(s):  
Matteo Vecellio ◽  
Elvezia Maria Paraboschi ◽  
Angela Ceribelli ◽  
Natasa Isailovic ◽  
Francesca Motta ◽  
...  

Background: Psoriatic disease is a multifactorial inflammatory condition spanning from skin and nail psoriasis (Pso) to spine and joint involvement characterizing psoriatic arthritis (PsA). Monozygotic twins provide a model to investigate genetic, early life environmental exposure and stochastic influences to complex diseases, mainly mediated by epigenetics.Methods: We performed a genome-wide DNA methylation study on whole blood of monozygotic twins from 7 pairs discordant for Pso/PsA using the Infinium Methylation EPIC array (Illumina). MeDiP—qPCR was used to confirm specific signals. Data were replicated in an independent cohort of seven patients with Pso/PsA and 3 healthy controls. Transcriptomic profiling was performed by RNAsequence on the same 7 monozygotic twin pairs.Results: We identified 2,564 differentially methylated positions between psoriatic disease and controls, corresponding to 1,703 genes, 59% within gene bodies. There were 19 regions with at least two DMPs within 1 kb of distance and significant within-pair Δβ-values (p < 0.005), among them SNX25, BRG1 and SMAD3 genes, all involved in TGF-β signaling pathway, were identified. Co-expression analyses on transcriptome data identified IL-6/JAK/STAT3 and TNF-α pathways as important signaling axes involved in the disease, and they also suggested an altered glucose metabolism in patients’ immune cells, characteristic of pro-inflammatory T lymphocytes.Conclusion: The study suggests the presence of an epigenetic signature in affected individuals, pointing to genes involved in immunological and inflammatory responses. This result is also supported by transcriptome data, that altogether suggest a higher activation state of the immune system, that could promote the disease status.


Author(s):  
Sarah Warkentin ◽  
Milton Severo ◽  
Alison Fildes ◽  
Andreia Oliveira

Abstract Purpose Given the variability in adiposity despite ubiquitous exposure to obesogenic food environments, it has been suggested that individuals respond in divergent ways to the environment they live in. The food environment becomes more ‘permissive’ as children age; therefore, genetic predisposition for a more avid appetite can be better expressed, influencing dietary quality, energy intake and weight gain. Our aim was to explore the genetic and environmental contribution of variations on appetitive traits in a sample of 10-year-old Portuguese children. Methods Participants were twins enrolled in the Generation XXI birth cohort (n = 86 pairs). Parents reported twin’s zygosity and child appetitive traits at 10 years of age through the Children’s Eating Behavior Questionnaire. Intra-class correlations (ICCs) for all appetitive traits were calculated for monozygotic and dizygotic twins separately to examine patterns of resemblance, and structural equation modeling was conducted aiming to estimate the genetic (A), shared (C) and non-shared (E) environmental variances. Results Moderate to strong heritability were found for child appetitive traits, with higher ICCs among monozygotic twin pairs. For all appetitive traits, with the exception of emotional undereating, genetic and non-shared environmental effects contributed to appetite variability. For emotional undereating, environmental effects seem to be more important than genetic effects (C: 0.81; 95% CI 0.71; 0.88 and E: 0.19; 95% CI 0.12; 0.29). Conclusion There was a significant genetic contribution, followed by non-shared environmental contribution, towards variation in appetitive traits in school-age children. Variation in emotional undereating was primarily explained by shared and non-shared environmental factors. Level of evidence Evidence obtained from well-designed cohort or case–control analytic studies.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2278-2278
Author(s):  
Eric M. Nickels ◽  
Shaobo Li ◽  
Katti Arroyo ◽  
Swe Swe Myint ◽  
Adam J. de Smith ◽  
...  

Abstract Background: Aberrant patterns of DNA methylation constitute a key feature of pediatric acute lymphoblastic leukemia (ALL) at diagnosis, however its role as a predisposing or early contributor to the development of ALL remains unknown. We employed a discordant monozygotic twin model to identify epigenetic variation associated with future development of pediatric ALL through evaluation of DNA methylation at birth. Methods: Twin pairs discordant for the development of pediatric ALL were identified using linked data from the California Cancer Registry and California Birth Statistical Master File spanning from 1989 to 2015. Archived dried neonatal blood spots were obtained from 86 same-gender twin pairs with available materials from the California Biobank Program. Following isolation of genomic DNA from DBS samples, monozygosity was confirmed in 43 of 86 twin pairs through an identity-by-descent analysis from a genome-wide SNP-array. Epigenome-wide DNA methylation assessment of the 43 discordant monozygotic twin pairs was conducted using the Illumina Infinium MethylationEPIC BeadChip kit (Illumina, San Diego, CA, USA). Data preprocessing and quality control measures were conducted in R, using SeSAMe for data normalization. Two twin pairs were omitted due to failure to pass quality control measures. Within-pair analysis was conducted through identification of array probes with absolute differences in methylation beta values greater than 15% between case and control siblings of a twin pair unit. Differentially methylated probes (DMP) were identified using a conditional logistic regression model accounting for array-specific variation, nucleated cell proportions, and appropriate control for the paired nature of the dataset. Differentially methylated regions (DMR) were defined by regional correlation of p-values from the conditional logistic regression model. Gene set enrichment analysis was conducted on significant probes identified through the within pair and regression analysis. Results: The discordant twin cohort (n = 41 pairs) included 24 female and 17 male pairs. Median gestational age was 258 days, ranging from 184 to 306 days. Age of diagnosis in the case twin ranged from <1 to 23 years (median = 5). There was no significant association between birthweight and case status (paired Wilcoxon signed rank test p = 0.22). No significant differences in nucleated cell proportions were identified in deconvolution analysis. Within-pair analysis identified a total of 18,001 probes with absolute methylation variation greater than 15% across the 41 twin pairs, with 3,984 recurrently variable across more than one pair. Gene ontology analysis of these recurrently variable sites revealed an enrichment of immune-related processes in 7 of the top 15 terms with nominal p-value <0.05, though no terms were significant after correction for multiple comparisons. Conditional logistic regression was conducted on 37 twin pairs, with T-cell cases (n=4) omitted to improve data resolution. This resulted in 240 significant DMPs with p-values below an FDR threshold of 0.05. Of these significant probes, 20 associate with genes previously reported to have altered DNA methylation in ALL at diagnosis. Regional analysis identified 10 significant DMRs with adjusted p-values below 0.05, with the top association encompassing a 454bp region on chromosome 6 located near TRIM39-RPP21 (adjusted p-value 2.39e-05). Notably, conditional regression analysis revealed a significant negative bias in coefficients (409,812 of 710,010 probes, binomial exact test p <2.2e-16), indicating a global tendency toward hypomethylation in cases compared to unaffected siblings (Figure 1). The strength of this bias was greater in probes associated with open sea regions compared to those in island regions, as well as promoter-associated probes. Conclusions: This novel analysis of DNA methylation at birth in ALL-discordant monozygotic twins identified sites of differential methylation associated with immune regulation. In addition, these results provide evidence of an association between global DNA hypomethylation and future development of ALL in one member of a genetically identical twin pair. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


Author(s):  
Iradj Sobhani ◽  
Emma Bergsten ◽  
Cecile Charpy ◽  
Mathias Chamaillard ◽  
Denis Mestivier

Colorectal carcinoma (CRC) is a common disease, the incidence of which is increasing according to Western lifestyle; it remains to have a poor prognosis. Western nutriments are presumed to induce mild inflammation within the colonic mucosa, resulting in the accumulation of DNA alterations in colonocytes through a multistage carcinogenesis process. This suggests that most CRCs are related to the environment. Of interest, fecal microbiota composition has been shown yielding a novel approach regarding how environment changes may impact health and disease. Here, we compare whole shotgun metagenomic gut microbiota of two monozygotic twin sisters, one of whom is suffering from an advance colorectal tumor with a profound disequilibrium of the composition of the gut microbiota due to the overexpression of virulent bacteria such as E. coli, Shigella, and Clostridium species in the colon cancer patient’s feces contrasting with low levels of bacterial species such as Faecalibacterium and Akkermansia usually enriched in the healthy adults’ microbial flora. The disequilibrium in microbiota of the CRC patient’s feces as compared to her monozygotic twin sister is linked to inflammatory and immune cell infiltrates in the patient’s colonic tissue. We speculate on the role of microbiota disequilibrium on the immune-tolerant cell infiltrate within CRCs.


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