TY - GEN A1 - Lu, Yong-Ping A1 - Reichetzeder, Christoph A1 - Prehn, Cornelia A1 - Yin, Liang-Hong A1 - Yun, Chen A1 - Zeng, Shufei A1 - Chu, Chang A1 - Adamski, Jerzy A1 - Hocher, Berthold T1 - Cord blood Lysophosphatidylcholine 16:1 is positively associated with birth weight T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Background/Aims: Impaired birth outcomes, like low birth weight, have consistently been associated with increased disease susceptibility to hypertension in later life. Alterations in the maternal or fetal metabolism might impact on fetal growth and influence birth outcomes. Discerning associations between the maternal and fetal metabolome and surrogate parameters of fetal growth could give new insight into the complex relationship between intrauterine conditions, birth outcomes, and later life disease susceptibility. Methods: Using flow injection tandem mass spectrometry, targeted metabolomics was performed in serum samples obtained from 226 mother/child pairs at delivery. Associations between neonatal birth weight and concentrations of 163 maternal and fetal metabolites were analyzed. Results: After FDR adjustment using the Benjamini-Hochberg procedure lysophosphatidylcholines (LPC) 14:0, 16:1, and 18:1 were strongly positively correlated with birth weight. In a stepwise linear regression model corrected for established confounding factors of birth weight, LPC 16: 1 showed the strongest independent association with birth weight (CI: 93.63 - 168.94; P = 6.94x10(-11)). The association with birth weight was stronger than classical confounding factors such as offspring sex (CI: - 258.81- -61.32; P = 0.002) and maternal smoking during pregnancy (CI: -298.74 - -29.51; P = 0.017). Conclusions: After correction for multiple testing and adjustment for potential confounders, LPC 16:1 showed a very strong and independent association with birth weight. The underlying molecular mechanisms linking fetal LPCs with birth weight need to be addressed in future studies. (c) 2018 The Author(s) Published by S. Karger AG, Basel T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 631 KW - metabolomics KW - Lysophosphatidylcholine KW - birth weight KW - DOHaD KW - hypertension KW - Type 2 Diabetes Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-424566 SN - 1866-8372 IS - 631 ER - TY - GEN A1 - Dwi Putra, Sulistyo Emantoko A1 - Reichetzeder, Christoph A1 - Hasan, Ahmed Abdallah Abdalrahman Mohamed A1 - Slowinski, Torsten A1 - Chu, Chang A1 - Krämer, Bernhard K. A1 - Kleuser, Burkhard A1 - Hocher, Berthold T1 - Being born large for gestational age is associated with increased global placental DNA methylation T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Being born small (SGA) or large for gestational age (LGA) is associated with adverse birth outcomes and metabolic diseases in later life of the offspring. It is known that aberrations in growth during gestation are related to altered placental function. Placental function is regulated by epigenetic mechanisms such as DNA methylation. Several studies in recent years have demonstrated associations between altered patterns of DNA methylation and adverse birth outcomes. However, larger studies that reliably investigated global DNA methylation are lacking. The aim of this study was to characterize global placental DNA methylation in relationship to size for gestational age. Global DNA methylation was assessed in 1023 placental samples by LC-MS/MS. LGA offspring displayed significantly higher global placental DNA methylation compared to appropriate for gestational age (AGA; p<0.001). ANCOVA analyses adjusted for known factors impacting on DNA methylation demonstrated an independent association between placental global DNA methylation and LGA births (p<0.001). Tertile stratification according to global placental DNA methylation levels revealed a significantly higher frequency of LGA births in the third tertile. Furthermore, a multiple logistic regression analysis corrected for known factors influencing birth weight highlighted an independent positive association between global placental DNA methylation and the frequency of LGA births (p=0.001). T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1405 KW - fetal origins hypothesis KW - birth weight KW - repetitive elements KW - glucocorticoid receptor KW - nutrient transport KW - growth restriction KW - later health KW - pregnancy KW - genes KW - patterns Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-516289 SN - 1866-8372 IS - 1 ER - TY - GEN A1 - Beaumont, Robin N. A1 - Warrington, Nicole M. A1 - Cavadino, Alana A1 - Tyrrell, Jessica A1 - Nodzenski, Michael A1 - Horikoshi, Momoko A1 - Geller, Frank A1 - Myhre, Ronny A1 - Richmond, Rebecca C. A1 - Paternoster, Lavinia A1 - Bradfield, Jonathan P. A1 - Kreiner-Møller, Eskil A1 - Huikari, Ville A1 - Metrustry, Sarah A1 - Lunetta, Kathryn L. A1 - Painter, Jodie N. A1 - Hottenga, Jouke-Jan A1 - Allard, Catherine A1 - Barton, Sheila J. A1 - Espinosa, Ana A1 - Marsh, Julie A. A1 - Potter, Catherine A1 - Zhang, Ge A1 - Ang, Wei A1 - Berry, Diane J. A1 - Bouchard, Luigi A1 - Das, Shikta A1 - Hakonarson, Hakon A1 - Heikkinen, Jani A1 - Helgeland, Øyvind A1 - Hocher, Berthold A1 - Hofman, Albert A1 - Inskip, Hazel M. A1 - Jones, Samuel E. A1 - Kogevinas, Manolis A1 - Lind, Penelope A. A1 - Marullo, Letizia A1 - Medland, Sarah E. A1 - Murray, Anna A1 - Murray, Jeffrey C. A1 - Njølstad, Pa ̊l R. A1 - Nohr, Ellen A. A1 - Reichetzeder, Christoph A1 - Ring, Susan M. A1 - Ruth, Katherine S. A1 - Santa-Marina, Loreto A1 - Scholtens, Denise M. A1 - Sebert, Sylvain A1 - Sengpiel, Verena A1 - Tuke, Marcus A. A1 - Vaudel, Marc A1 - Weedon, Michael N. A1 - Willemsen, Gonneke A1 - Wood, Andrew R. A1 - Yaghootkar, Hanieh A1 - Muglia, Louis J. A1 - Bartels, Meike A1 - Relton, Caroline L. A1 - Pennell, Craig E. A1 - Chatzi, Leda A1 - Estivill, Xavier A1 - Holloway, John W. A1 - Boomsma, Dorret I. A1 - Montgomery, Grant W. A1 - Murabito, Joanne M. A1 - Spector, Tim D. A1 - Power, Christine A1 - Ja ̈rvelin, Marjo-Ritta A1 - Bisgaard, Hans A1 - Grant, Struan F.A. A1 - Sørensen, Thorkild I.A. A1 - Jaddoe, Vincent W. A1 - Jacobsson, Bo A1 - Melbye, Mads A1 - McCarthy, Mark I. A1 - Hattersley, Andrew T. A1 - Hayes, M. Geoffrey A1 - Frayling, Timothy M. A1 - Hivert, Marie-France A1 - Felix, Janine F. A1 - Hyppo ̈nen, Elina A1 - Lowe, William L. , Jr A1 - Evans, David M. A1 - Lawlor, Debbie A. A1 - Feenstra, Bjarke A1 - Freathy, Rachel M. T1 - Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother–child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 Â 10 À8 . In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 628 KW - alleles KW - birth weight KW - fetus KW - genotype KW - mothers KW - single nucleotide polymorphism KW - genetics KW - duration of gestation KW - genome-wide association study KW - offspring KW - biobanks Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-423100 SN - 1866-8372 IS - 628 ER -