@article {440, title = {Identical twins carry a persistent epigenetic signature of early genome programming}, journal = {Nature Communications}, volume = {12}, year = {2021}, pages = {5618}, abstract = {

Monozygotic (MZ) twins and higher-order multiples arise when a zygote splits during pre-implantation stages of development. The mechanisms underpinning this event have remained a mystery. Because MZ twinning rarely runs in families, the leading hypothesis is that it occurs at random. Here, we show that MZ twinning is strongly associated with a stable DNA methylation signature in adult somatic tissues. This signature spans regions near telomeres and centromeres, Polycomb-repressed regions and heterochromatin, genes involved in cell-adhesion, WNT signaling, cell fate, and putative human metastable epialleles. Our study also demonstrates a never-anticipated corollary: because identical twins keep a lifelong molecular signature, we can retrospectively diagnose if a person was conceived as monozygotic twin.

}, doi = {10.1038/s41467-021-25583-7}, author = {van Dongen, Jenny and Gordon, Scott D and McRae, Allan F and Odintsova, Veronika V and Mbarek, Hamdi and Breeze, Charles E and Sugden, Karen and Lundgren, Sara and Castillo-Fernandez, Juan E and Hannon, Eilis and Moffitt, Terrie E and Hagenbeek, Fiona A and van Beijsterveldt, Catharina E M and Jan Hottenga, Jouke and Tsai, Pei-Chien and BIOS Consortium and Genetics of DNA Methylation Consortium and Min, Josine L and Hemani, Gibran and Ehli, Erik A and Paul, Franziska and Stern, Claudio D and Heijmans, Bastiaan T and Slagboom, P Eline and Daxinger, Lucia and van der Maarel, Silv{\`e}re M and de Geus, Eco J C and Willemsen, Gonneke and Montgomery, Grant W and Reversade, Bruno and Ollikainen, Miina and Kaprio, Jaakko and Spector, Tim D and Bell, Jordana T and Mill, Jonathan and Caspi, Avshalom and Martin, Nicholas G and Boomsma, Dorret I} } @article {424, title = {Genetics and not shared environment explains familial resemblance in adult metabolomics data}, journal = {Human Genetics}, volume = {23}, year = {2020}, pages = {145{\textendash}155}, abstract = {

Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term \&$\#$39;metabolomics\&$\#$39; refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented.

}, keywords = {classical twin design, enrichment analysis, heritability, metabolite classes, shared environment}, doi = {DOI: 10.1017/thg.2020.53}, author = {Pool, Ren{\'e} and Hagenbeek, Fiona A and Hendriks, Anne M and van Dongen, Jenny and Willemsen, Gonneke and de Geus, Eco and BBMRI Metabolomics Consortium and Willems van Dijk, Ko and Verhoeven, Aswin and Suchiman, H Eka and Beekman, Marian and Slagboom, P Eline and Harms, Amy C and Hankemeier, Thomas and Boomsma, Dorret I} } @article {427, title = {Heritability estimates for 361 blood metabolites across 40 genome-wide association studies}, journal = {Nature Communications}, volume = {11}, year = {2020}, pages = {39}, abstract = {

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50\% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify \>800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2total), and the proportion of heritability captured by known metabolite loci (h2Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.

}, doi = {DOI: 10.1038/s41467-019-13770-6}, author = {Hagenbeek, Fiona A and Pool, Ren{\'e} and van Dongen, Jenny and Draisma, Harmen H M and Jan Hottenga, Jouke and Willemsen, Gonneke and Abdellaoui, Abdel and Fedko, Iryna O and den Braber, Anouk and Visser, Pieter Jelle and de Geus, Eco J C N and Willems van Dijk, Ko and Verhoeven, Aswin and Suchiman, H Eka and Beekman, Marian and Slagboom, P Eline and van Duijn, Cornelia M and BBMRI Metabolomics Consortium and Harms, Amy C and Hankemeier, Thomas and Bartels, Meike and Nivard, Michel G and Boomsma, Dorret I} }