Project description:This data set represents a reanalysis of human blood plasma samples measured by SWATH-MS of 36 pairs of monozygotic and 22 pairs of dizygotic twins that were sampled at two longitudinal time points (Liu et al., 2015, PMID:25652787). The data were used to determine the overall quantitative variability of 4322 peptidoforms in the sample cohort and to assign the measured variability to heritability, environmental or longitudinal effects.
Project description:The MetaboHealth score is a highly informative health indicator in ageing studies and yet contains only a small number of metabolites. Here we estimate the heritability of the score in 726 monozygotic (MZ) and 450 dizygotic (DZ) twin pairs, and test for association with plasma proteins by comparing extreme scoring individuals selected from two large population cohorts -the Leiden Longevity Study (LLS) and the Rotterdam Study (RS) and discordant monozygotic twin pairs from the Netherlands Twin Register (NTR). The heritability for the MetaboHealth score was estimated at 40%. In 50 high and 50 low scoring MetaboHealth groups from LLS and RS, we uncovered significant differences in plasma proteins, notably in 3 (out of 15) cytokines (GDF15, IL6, and MIG), and 106 proteins (out of 289) as determined by Mass Spectrometry based proteomics analysis. A high MetaboHealth score associated with an increased level for 42 serum proteins, predominantly linked to inflammation and immune response, including CRP and HPT. A low score associated with decreased levels of 71 proteins enriched in high-density lipoprotein (HDL) remodeling and cholesterol transport pathways, featuring proteins such as APOA1, APOA2, APOA4, and TETN. In MZ twins selected for maximal discordance within a pair we found 68 serum proteins associated with the MetaboHealth score indicating that a minor part of the associations observed in LLS and RS is likely explained by genetic influences. Taken together, our study sheds light on the intricate interplay between MetaboHealth, plasma proteins, cytokines, and genetic influences, paving the way for future investigations aimed at optimizing this mortality risk indicator.
Project description:DNA methylation data for 479 women from 130 families including 66 monozygotic twin pairs, 66 dizygotic twin pairs and 215 sisters of twins.
Project description:The human plasma proteome is clinically highly significant and has been studied extensively because it is thought that its molecular makeup provides a window into the health state of an individual. However, neither the quantitative variability of the plasma proteome nor the origins of the variation are known. To determine the relative contributions of heritability, environmental and longitudinal factors to plasma proteome variability we systematically decomposed the biological variance of 1904 peptides defining 342 unique plasma protein profiles from 232 plasma samples that were collected with 2-7 year intervals from monozygotic (MZ) and dizygotic (DZ) twins. The data were collected via SWATH mass spectrometry (SWATH-MS), an emerging technology characterized by high degree of reproducibility and quantitative accuracy. The data indicate abundance variability is an important feature for different proteins among population, that the abundances of about 20% of plasma protein are considerably heritable, and that the degrees of genetic control and aging effects vary across specific biological processes. Moreover, we identified 13 cis- SNPs significantly influencing the abundance level of specific plasma proteins. These results substantially extend the understanding of the impact of heritability on the human proteomic dynamics and therefore have implications for the effective design of plasma-based biomarker studies.
Project description:Using the Infinium HM450 platform, we have performed a longitudinal study of DNA methylation at birth and age 18 months in DNA from buccal swabs from 10 monozygotic (MZ) and 5 dizygotic (DZ) twin pairs from the Peri/postnatal Epigenetic Twins Study (PETS) cohort.
Project description:The human gut microbiota harbors methanogens represented by the dominant archaeon, Methanobrevibacter smithii, a polyphyletic group of acetogens, and sulfate-reducing bacteria. Defining their roles in the H2-economy of the gut has potential therapeutic importance for modulating the efficiency of fermentation of dietary components. We quantified methanogens in fecal samples from 40 healthy adult female monozygotic(MZ) and 28 dizygotic(DZ) twin pairs, analyzed bacterial 16S rRNA datasets generated from their fecal samples to identify taxa that co-occur with methanogens, sequenced the genomes of 20 M. smithii strains isolated from families of MZ and DZ twins, and performed RNA-Seq of a subset of strains to identify their responses to varied formate concentrations. The concordance rate for methanogen carriage was significantly higher for MZ versus DZ twin pairs. Co-occurrence analysis revealed 22 bacterial species-level taxa positively correlated with methanogens: all but two were members of the Clostridiales, with several being, or related to, known hydrogen-producing and -consuming bacteria. The M. smithii pan-genome contains 987 genes conserved in all strains, and 1860 variably represented genes. Strains from MZ and DZ twin pairs had a similar degree of shared genes and SNPs, and were significantly more similar than strains isolated from mothers or members of other families. The 101 adhesin-like proteins(ALPs) in the pan-genome (45±6/strain) exhibit strain-specific differences in expression and responsiveness to formate. We hypothesize that M. smithii strains use their different repertoires of ALPs to create diversity in their metabolic niches, by allowing them to establish syntrophic relationships with bacterial partners with differing metabolic capabilities and patterns of co-occurrence These strains were isolated from human feces, but they are in pure culture now. All the information about each species is associated with the genome accession number Fecal samples from 40 healthy adult female monozygotic(MZ) and 28 dizygotic(DZ) twin pairs, analyzed bacterial 16S rRNA datasets generated from their fecal samples to identify taxa that co-occur with methanogens, sequenced the genomes of 20 M. smithii strains isolated from families of MZ and DZ twins, and performed RNA-Seq of a subset of strains to identify their responses to varied formate concentrations. Strains of Methanobrevibacter smithii were grown in vitro (modified MBC media) to mid-log phase, at 37°C in serum bottles pressurized with 80% hydrogen, 20% CO2 gasses at 30psi. Cells were harvested by centrifugation, and DNA was isolated by phenol-chloroform and ethanol precipitation.
Project description:By integrating data on the immune profiles of healthy monozygotic and dizygotic twin pairs we estimated the variance in CD25 expression by naïve Th cells to be largely driven by genetic and shared early environmental influences. Nonetheless, the Th cell subset expanded in MS twins, which was also elevated in non-twin MS patients , emerged independent of the individual genetic makeup. These cells expressed CNS-homing receptors, exhibited a dysregulated CD25-IL-2 axis, and their proliferative capacity positively correlated with MS severity . Together, the pair-matched analysis of the extended twin approach allowed us to discern genetically- and environmentally- determined features of an MS-associated immune signature.
Project description:Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic, shared and non-shared environmental factors to phenotypic variability. Using DNA methylation profiling of ~20,000 CpG sites as a phenotype, we have examined discordance levels in multiple tissues in neonatal twins. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs. Within-pair methylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. This was largely independent of distance from transcriptional start site in promoters without CpG islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of non-shared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic and other complex diseases. Finally, comparison of our data with that of several older twins, revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyse DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome.
Project description:Epigenetic misregulation is consistent with the various non-Mendelian features of Alzheimer's disease (AD) and may even play an etiological role in the disease. We performed DNA modification profiling of post-mortem brain samples from twins who differed for age of AD onset and buccal samples from twins who were discordant for AD at the time of sample collection. We performed DNA methylome analysis on frontal cortex, cerebellum, or buccal tissues from monozygotic twins and dizygotic twins discordant for Alzheimerâs disease (AD) or disease age of onset. DNA samples were enriched for unmodified fraction of the genome using DNA-modification sensitive restriction enzyme digestion followed by adaptor-mediated PCR. The enriched fractions were labelled with a fluorescent dye (Cy3) and hybridized onto the array with a common reference pool (Cy5).