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Behavior Genetics Jan 2024Nutrition and diet are key modifiable risk factors for the rising burden of non-communicable diseases like cardio-vascular diseases and diabetes in low- and middle-...
Nutrition and diet are key modifiable risk factors for the rising burden of non-communicable diseases like cardio-vascular diseases and diabetes in low- and middle- income countries (LMICs). The nutritional transition in dietary behaviours in LMICs has most likely contributed to this problem. Although traditionally assumed to be environmental, dietary choices are also genetically influenced. Twin study designs can be used to investigate the relative influence of genes and environment on nutrition intake, eating behaviours and associated psychological health. The overall aim of this project is to: provide proof-of-concept for the feasibility of using dietary (biomarker) data within the Children-of-Twin design in nutrition studies, develop laboratory skills and statistical genetic skills and establish a Sri Lankan-specific food composition database. Currently, a pilot study is being conducted with 304 individuals (38 Monozygotic twin pairs, 38 Dizygotic twin pairs and their male or female adult offspring). Questionnaire data on nutritional intake, eating behaviours, psychological well-being, physical health, and bio-specimens are being collected. A Sri Lankan-specific food composition database was developed, training sessions on macro and micro element analysis in biological samples and statistical genetics skills development were conducted and Community Engagement and Involvement programs were carried out in two districts of Sri Lanka.
Topics: Adult; Female; Humans; Male; Diseases in Twins; Feasibility Studies; Pilot Projects; Twins, Dizygotic; Twins, Monozygotic; Adult Children
PubMed: 38184818
DOI: 10.1007/s10519-023-10171-w -
Communications Biology Jan 2024The aesthetic values that individuals place on visual images are formed and shaped over a lifetime. However, whether the formation of visual aesthetic value is solely...
The aesthetic values that individuals place on visual images are formed and shaped over a lifetime. However, whether the formation of visual aesthetic value is solely influenced by environmental exposure is still a matter of debate. Here, we considered differences in aesthetic value emerging across three visual domains: abstract images, scenes, and faces. We examined variability in two major dimensions of ordinary aesthetic experiences: taste-typicality and evaluation-bias. We build on two samples from the Australian Twin Registry where 1547 and 1231 monozygotic and dizygotic twins originally rated visual images belonging to the three domains. Genetic influences explained 26% to 41% of the variance in taste-typicality and evaluation-bias. Multivariate analyses showed that genetic effects were partially shared across visual domains. Results indicate that the heritability of major dimensions of aesthetic evaluations is comparable to that of other complex social traits, albeit lower than for other complex cognitive traits. The exception was taste-typicality for abstract images, for which we found only shared and unique environmental influences. Our study reveals that diverse sources of genetic and environmental variation influence the formation of aesthetic value across distinct visual domains and provides improved metrics to assess inter-individual differences in aesthetic value.
Topics: Humans; Australia; Benchmarking; Environmental Exposure; Esthetics; Individuality
PubMed: 38184755
DOI: 10.1038/s42003-023-05710-4 -
MedRxiv : the Preprint Server For... Dec 2023Whether differences in lifestyle between co-twins are reflected in differences in their internal or external exposome profiles remains largely underexplored. We...
Whether differences in lifestyle between co-twins are reflected in differences in their internal or external exposome profiles remains largely underexplored. We therefore investigated whether within-pair differences in lifestyle were associated with within-pair differences in exposome profiles across four domains: the external exposome, proteome, metabolome and epigenetic age acceleration (EAA). For each domain, we assessed the similarity of co-twin profiles using Gaussian similarities in up to 257 young adult same-sex twin pairs (54% monozygotic). We additionally tested whether similarity in one domain translated into greater similarity in another. Results suggest that a lower degree of similarity in co-twins' exposome profiles was associated with greater differences in their behavior and substance use. The strongest association was identified between excessive drinking behavior and the external exposome. Overall, our study demonstrates how social behavior and especially substance use are connected to the internal and external exposomes, while controlling for familial confounders.
PubMed: 38168348
DOI: 10.1101/2023.12.12.23299868 -
Open Life Sciences 2023According to Mendel's law of genetic separation, there must be a certain blood relationship between members of the same family, and two individuals with blood relations...
According to Mendel's law of genetic separation, there must be a certain blood relationship between members of the same family, and two individuals with blood relations must have the following three situations, that is, there are two homologous genes (I denotes), one homologous gene (T denotes), and no homologous genes (O denotes), which is the ITO index for calculating the blood relationship between two individuals. The AGGU Expressmarker 22 kit, ABI 3500 genetic analyzer, and GeneMapper ID-X v1.5 software were used to statistically analyze the ITO index of the gene locus of 5 kinds of samples, 28 pairs of monozygotic twins (MT), 4,000 pairs of parent-offspring (PO), 392 pairs of full sibling (FS), 138 pairs of half-siblings (HS) (including grandchildren, uncles, and nephews) and 3,500 pairs of unrelated individuals (UI). Observing the median distribution of ITO index found that from MT, PO, FS, HS to UI, the more distant the kinship, the smaller the ITO index. Full sibling index (FSI)/half-sibling index (HSI) ≥ 1 can be used as the FS discriminant standard, FSI/HSI < 1 can be used as the HS discriminant standard. According to the distance of kinship, from the direction of MT, PO, FS, HS, and UI, the proportion of the maximum ITO index of the same type of sample in the true kinship index item showed a decreasing trend. ITO index is an important statistical means to identify the kinship between two individuals, according to which the ITO index can accurately determine the kinship between individuals, which has high application value. MT index is not 0 to identify relatives as MT, PO index is an important indicator to distinguish between relatives as PO and FS. The critical values of ITO index discriminant values for UI and HS need to be further studied.
PubMed: 38162390
DOI: 10.1515/biol-2022-0786 -
BMC Medicine Dec 2023The influence of genetics and environment on the association of the plasma proteome with body mass index (BMI) and changes in BMI remains underexplored, and the links to...
BACKGROUND
The influence of genetics and environment on the association of the plasma proteome with body mass index (BMI) and changes in BMI remains underexplored, and the links to other omics in these associations remain to be investigated. We characterized protein-BMI trajectory associations in adolescents and adults and how these connect to other omics layers.
METHODS
Our study included two cohorts of longitudinally followed twins: FinnTwin12 (N = 651) and the Netherlands Twin Register (NTR) (N = 665). Follow-up comprised 4 BMI measurements over approximately 6 (NTR: 23-27 years old) to 10 years (FinnTwin12: 12-22 years old), with omics data collected at the last BMI measurement. BMI changes were calculated in latent growth curve models. Mixed-effects models were used to quantify the associations between the abundance of 439 plasma proteins with BMI at blood sampling and changes in BMI. In FinnTwin12, the sources of genetic and environmental variation underlying the protein abundances were quantified by twin models, as were the associations of proteins with BMI and BMI changes. In NTR, we investigated the association of gene expression of genes encoding proteins identified in FinnTwin12 with BMI and changes in BMI. We linked identified proteins and their coding genes to plasma metabolites and polygenic risk scores (PRS) applying mixed-effects models and correlation networks.
RESULTS
We identified 66 and 14 proteins associated with BMI at blood sampling and changes in BMI, respectively. The average heritability of these proteins was 35%. Of the 66 BMI-protein associations, 43 and 12 showed genetic and environmental correlations, respectively, including 8 proteins showing both. Similarly, we observed 7 and 3 genetic and environmental correlations between changes in BMI and protein abundance, respectively. S100A8 gene expression was associated with BMI at blood sampling, and the PRG4 and CFI genes were associated with BMI changes. Proteins showed strong connections with metabolites and PRSs, but we observed no multi-omics connections among gene expression and other omics layers.
CONCLUSIONS
Associations between the proteome and BMI trajectories are characterized by shared genetic, environmental, and metabolic etiologies. We observed few gene-protein pairs associated with BMI or changes in BMI at the proteome and transcriptome levels.
Topics: Humans; Adolescent; Young Adult; Adult; Child; Body Mass Index; Proteome; Multiomics; Twins, Monozygotic; Longitudinal Studies
PubMed: 38129841
DOI: 10.1186/s12916-023-03198-7 -
Personality Neuroscience 2023The present study examines whether neuroticism is predicted by genetic vulnerability, summarized as polygenic risk score for neuroticism (PRS), in interaction with...
The present study examines whether neuroticism is predicted by genetic vulnerability, summarized as polygenic risk score for neuroticism (PRS), in interaction with bullying, parental bonding, and childhood adversity. Data were derived from a general population adolescent and young adult twin cohort. The final sample consisted of 202 monozygotic and 436 dizygotic twins and 319 twin pairs. The Short Eysenck Personality questionnaire was used to measure neuroticism. PRS was trained on the results from the Genetics of Personality Consortium (GPC) and United Kingdom Biobank (UKB) cohorts, yielding two different PRS. Multilevel mixed-effects models were used to analyze the main and interacting associations of PRS, childhood adversity, bullying, and parental bonding style with neuroticism. We found no evidence of gene-environment correlation. PRS thresholds of .005 and .2 were chosen, based on GPC and UKB datasets, respectively. After correction for confounders, all the individual variables were associated with the expression of neuroticism: both PRS from GPC and UKB, childhood adversity, maternal bonding, paternal bonding, and bullying in primary school and secondary school. However, the results indicated no evidence for gene-environment interaction in this cohort. These results suggest that genetic vulnerability on the one hand and negative life events (childhood adversity and bullying) and positive life events (optimal parental bonding) on the other represent noninteracting pathways to neuroticism.
PubMed: 38107775
DOI: 10.1017/pen.2023.2 -
BMC Medicine Dec 2023Major psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BPD) are complex genetic mental illnesses. Their non-Mendelian features, such as those...
BACKGROUND
Major psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BPD) are complex genetic mental illnesses. Their non-Mendelian features, such as those observed in monozygotic twins discordant for SCZ or BPD, are likely complicated by environmental modifiers of genetic effects. 5-Hydroxymethylcytosine (5hmC) is an important epigenetic mark in gene regulation, and whether it is linked to genetic variants that contribute to non-Mendelian features remains largely unexplored.
METHODS
We combined the 5hmC-selective chemical labeling method (5hmC-seq) and whole-genome sequencing (WGS) analysis of peripheral blood DNA obtained from monozygotic (MZ) twins discordant for SCZ or BPD to identify allelic imbalances in hydroxymethylome maps, and examined association of allele-specific hydroxymethylation (AShM) transition with disease susceptibility based on Bayes factors (BF) derived from the Bayesian generalized additive linear mixed model. We then performed multi-omics integrative analysis to determine the molecular pathogenic basis of those AShM sites. We finally employed luciferase reporter, CRISPR/Cas9 technology, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), PCR, FM4-64 imaging analysis, and RNA sequencing to validate the function of interested AShM sites in the human neuroblastoma SK-N-SH cells and human embryonic kidney 293T (HEK293T) cells.
RESULTS
We identified thousands of genetic variants associated with AShM imbalances that exhibited phenotypic variation-associated AShM changes at regulatory loci. These AShM marks showed plausible associations with SCZ or BPD based on their effects on interactions among transcription factors (TFs), DNA methylation levels, or other epigenomic marks and thus contributed to dysregulated gene expression, which ultimately increased disease susceptibility. We then validated that competitive binding of POU3F2 on the alternative allele at the AShM site rs4558409 (G/T) in PLLP-enhanced PLLP expression, while the hydroxymethylated alternative allele, which alleviated the POU3F2 binding activity at the rs4558409 site, might be associated with the downregulated PLLP expression observed in BPD or SCZ. Moreover, disruption of rs4558409 promoted neural development and vesicle trafficking.
CONCLUSION
Our study provides a powerful strategy for prioritizing regulatory risk variants and contributes to our understanding of the interplay between genetic and epigenetic factors in mediating SCZ or BPD susceptibility.
Topics: Humans; Bayes Theorem; Alleles; Twins, Monozygotic; HEK293 Cells; DNA Methylation; Schizophrenia; Genetic Predisposition to Disease; Epigenesis, Genetic
PubMed: 38082312
DOI: 10.1186/s12916-023-03177-y -
Alzheimer's & Dementia : the Journal of... Mar 2024Dementia predicts increased mortality. We used case-control and co-twin control models to investigate genetic and shared environmental influences on this association.
INTRODUCTION
Dementia predicts increased mortality. We used case-control and co-twin control models to investigate genetic and shared environmental influences on this association.
METHODS
Case-control design, including 987 twins with dementia and 2938 age- and sex-matched controls in the Swedish Twin Registry. Co-twin control design, including 90 monozygotic (MZ) and 288 dizygotic (DZ) twin pairs discordant for dementia. To test for genetic and environmental confounding, differences were examined in mortality risk between twins with dementia and their matched or co-twin controls.
RESULTS
Twins with dementia showed greater mortality risk than age- and sex-matched controls (HR = 2.02 [1.86, 2.18]). Mortality risk is significantly elevated but attenuated substantially in discordant twin pairs, for example, comparing MZ twins with dementia to their co-twin controls (HR = 1.48 [1.08, 2.04]).
DISCUSSION
Findings suggest that genetic factors partially confound the association between dementia and mortality and provide an alternative hypothesis to increased mortality due to dementia itself. Highlights We studied dementia and mortality in twin pairs discordant for dementia. People without dementia outlived people with dementia. Identical twins with dementia and their co-twin controls had similar survival time. Findings suggest genotype may explain the link between dementia and mortality.
Topics: Aged; Humans; Dementia; Genotype; Sweden; Twins, Dizygotic; Twins, Monozygotic; Male; Female
PubMed: 38078564
DOI: 10.1002/alz.13553 -
Oman Journal of Ophthalmology 2023Mirror-image is a term to describe a physical characteristic of some identical twins that appear asymmetrically on opposite sides as if they are looking in a mirror....
Mirror-image is a term to describe a physical characteristic of some identical twins that appear asymmetrically on opposite sides as if they are looking in a mirror. Mirror-image anisometropia in monozygotic twins was previously reported in the ophthalmic literature. In this article, we describe a case of mirror-image hypermetropic anisometropia in siblings aged 8 and 5 years old. Nontwin brothers, 8 and 5 years old, with mirror-image hypermetropic anisometropia, were referred to the pediatric ophthalmology clinic. Corrected distant visual acuity was 20/20 (ocula dextra [OD]), 20/60 (ocula sinistra [OS]) in the older brother, and 20/50 (OD), 20/20 (OS) in the younger brother. Cycloplegic refraction was + 3.5 - 1.25 × 180 (OD), +7.75 - 1.5 × 30 (OS), and + 7.0 - 0.75 × 20 (OD), +2.0 - 1.0 × 170 (OS) in the older and younger brother, respectively. The axial length difference between the two eyes was 1.47 mm in the older and 2.01 mm in the younger brother. Hypermetropic anisometropia that may lead to anisometropic amblyopia may happen in nontwin brothers. This emphasizes the importance of complete ophthalmologic examination in the siblings of all patients with anisometropia.
PubMed: 38059112
DOI: 10.4103/ojo.ojo_52_23