Dokument-ID Dokumenttyp Verfasser/Autoren Herausgeber Haupttitel Abstract Auflage Verlagsort Verlag Erscheinungsjahr Seitenzahl Schriftenreihe Titel Schriftenreihe Bandzahl ISBN Quelle der Hochschulschrift Konferenzname Quelle:Titel Quelle:Jahrgang Quelle:Heftnummer Quelle:Erste Seite Quelle:Letzte Seite URN DOI Abteilungen OPUS4-49661 Wissenschaftlicher Artikel Warrington, Nicole; Beaumont, Robin; Horikoshi, Momoko; Day, Felix R.; Helgeland, Øyvind; Laurin, Charles; Bacelis, Jonas; Peng, Shouneng; Hao, Ke; Feenstra, Bjarke; Wood, Andrew R.; Mahajan, Anubha; Tyrrell, Jessica; Robertson, Neil R.; Rayner, N. William; Qiao, Zhen; Moen, Gunn-Helen; Vaudel, Marc; Marsit, Carmen; Chen, Jia; Nodzenski, Michael; Schnurr, Theresia M.; Zafarmand, Mohammad Hadi; Bradfield, Jonathan P.; Grarup, Niels; Kooijman, Marjolein N.; Li-Gao, Ruifang; Geller, Frank; Ahluwalia, Tarunveer Singh; Paternoster, Lavinia; Rueedi, Rico; Huikari, Ville; Hottenga, Jouke-Jan; Lyytikäinen, Leo-Pekka; Cavadino, Alana; Metrustry, Sarah; Cousminer, Diana L.; Wu, Ying; Thiering, Elisabeth Paula; Wang, Carol A.; Have, Christian Theil; Vilor-Tejedor, Natalia; Joshi, Peter K.; Painter, Jodie N.; Ntalla, Ioanna; Myhre, Ronny; Pitkänen, Niina; van Leeuwen, Elisabeth M.; Joro, Raimo; Lagou, Vasiliki; Richmond, Rebecca C.; Espinosa, Ana; Barton, Sheila J.; Inskip, Hazel M.; Holloway, John W.; Santa-Marina, Loreto; Estivill, Xavier; Ang, Wei; Marsh, Julie A.; Reichetzeder, Christoph; Marullo, Letizia; Hocher, Berthold; Lunetta, Kathryn L.; Murabito, Joanne M.; Relton, Caroline L.; Kogevinas, Manolis; Chatzi, Leda; Allard, Catherine; Bouchard, Luigi; Hivert, Marie-France; Zhang, Ge; Muglia, Louis J.; Heikkinen, Jani; Morgen, Camilla S.; van Kampen, Antoine H. C.; van Schaik, Barbera D. C.; Mentch, Frank D.; Langenberg, Claudia; Scott, Robert A.; Zhao, Jing Hua; Hemani, Gibran; Ring, Susan M.; Bennett, Amanda J.; Gaulton, Kyle J.; Fernandez-Tajes, Juan; van Zuydam, Natalie R.; Medina-Gomez, Carolina; de Haan, Hugoline G.; Rosendaal, Frits R.; Kutalik, Zoltán; Marques-Vidal, Pedro; Das, Shikta; Willemsen, Gonneke; Mbarek, Hamdi; Müller-Nurasyid, Martina; Standl, Marie; Appel, Emil V. R.; Fonvig, Cilius Esmann; Trier, Caecilie; van Beijsterveldt, Catharina E. M.; Murcia, Mario; Bustamante, Mariona; Bonàs-Guarch, Sílvia; Hougaard, David M.; Mercader, Josep M.; Linneberg, Allan; Schraut, Katharina E.; Lind, Penelope A.; Medland, Sarah Elizabeth; Shields, Beverley M.; Knight, Bridget A.; Chai, Jin-Fang; Panoutsopoulou, Kalliope; Bartels, Meike; Sánchez, Friman; Stokholm, Jakob; Torrents, David; Vinding, Rebecca K.; Willems, Sara M.; Atalay, Mustafa; Chawes, Bo L.; Kovacs, Peter; Prokopenko, Inga; Tuke, Marcus A.; Yaghootkar, Hanieh; Ruth, Katherine S.; Jones, Samuel E.; Loh, Po-Ru; Murray, Anna; Weedon, Michael N.; Tönjes, Anke; Stumvoll, Michael; Michaelsen, Kim Fleischer; Eloranta, Aino-Maija; Lakka, Timo A.; van Duijn, Cornelia M.; Kiess, Wieland; Koerner, Antje; Niinikoski, Harri; Pahkala, Katja; Raitakari, Olli T.; Jacobsson, Bo; Zeggini, Eleftheria; Dedoussis, George V.; Teo, Yik-Ying; Saw, Seang-Mei; Montgomery, Grant W.; Campbell, Harry; Wilson, James F.; Vrijkotte, Tanja G. M.; Vrijheid, Martine; de Geus, Eco J. C. N.; Hayes, M. Geoffrey; Kadarmideen, Haja N.; Holm, Jens-Christian; Beilin, Lawrence J.; Pennell, Craig E.; Heinrich, Joachim; Adair, Linda S.; Borja, Judith B.; Mohlke, Karen L.; Eriksson, Johan G.; Widen, Elisabeth E.; Hattersley, Andrew T.; Spector, Tim D.; Kaehoenen, Mika; Viikari, Jorma S.; Lehtimaeki, Terho; Boomsma, Dorret I.; Sebert, Sylvain; Vollenweider, Peter; Sorensen, Thorkild I. A.; Bisgaard, Hans; Bonnelykke, Klaus; Murray, Jeffrey C.; Melbye, Mads; Nohr, Ellen A.; Mook-Kanamori, Dennis O.; Rivadeneira, Fernando; Hofman, Albert; Felix, Janine F.; Jaddoe, Vincent W. V.; Hansen, Torben; Pisinger, Charlotta; Vaag, Allan A.; Pedersen, Oluf; Uitterlinden, Andre G.; Jarvelin, Marjo-Riitta; Power, Christine; Hypponen, Elina; Scholtens, Denise M.; Lowe, William L.; Smith, George Davey; Timpson, Nicholas J.; Morris, Andrew P.; Wareham, Nicholas J.; Hakonarson, Hakon; Grant, Struan F. A.; Frayling, Timothy M.; Lawlor, Debbie A.; Njolstad, Pal R.; Johansson, Stefan; Ong, Ken K.; McCarthy, Mark I.; Perry, John R. B.; Evans, David M.; Freathy, Rachel M. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming. New York Nature Publ. Group 2019 17 Nature genetics 51 5 804 + Institut für Ernährungswissenschaft OPUS4-53521 Wissenschaftlicher Artikel Beaumont, Robin N.; Warrington, Nicole M.; Cavadino, Alana; Tyrrell, Jessica; Nodzenski, Michael; Horikoshi, Momoko; Geller, Frank; Myhre, Ronny; Richmond, Rebecca C.; Paternoster, Lavinia; Bradfield, Jonathan P.; Kreiner-Moller, Eskil; Huikari, Ville; Metrustry, Sarah; Lunetta, Kathryn L.; Painter, Jodie N.; Hottenga, Jouke-Jan; Allard, Catherine; Barton, Sheila J.; Espinosa, Ana; Marsh, Julie A.; Potter, Catherine; Zhang, Ge; Ang, Wei; Berry, Diane J.; Bouchard, Luigi; Das, Shikta; Hakonarson, Hakon; Heikkinen, Jani; Helgeland, Oyvind; Hocher, Berthold; Hofman, Albert; Inskip, Hazel M.; Jones, Samuel E.; Kogevinas, Manolis; Lind, Penelope A.; Marullo, Letizia; Medland, Sarah E.; Murray, Anna; Murray, Jeffrey C.; Njolstad, Pal R.; Nohr, Ellen A.; Reichetzeder, Christoph; Ring, Susan M.; Ruth, Katherine S.; Santa-Marina, Loreto; Scholtens, Denise M.; Sebert, Sylvain; Sengpiel, Verena; Tuke, Marcus A.; Vaudel, Marc; Weedon, Michael N.; Willemsen, Gonneke; Wood, Andrew R.; Yaghootkar, Hanieh; Muglia, Louis J.; Bartels, Meike; Relton, Caroline L.; Pennell, Craig E.; Chatzi, Leda; Estivill, Xavier; Holloway, John W.; Boomsma, Dorret I.; Montgomery, Grant W.; Murabito, Joanne M.; Spector, Tim D.; Power, Christine; Jarvelin, Marjo-Ritta; Bisgaard, Hans; Grant, Struan F. A.; Sorensen, Thorkild I. A.; Jaddoe, Vincent W.; Jacobsson, Bo; Melbye, Mads; McCarthy, Mark I.; Hattersley, Andrew T.; Hayes, M. Geoffrey; Frayling, Timothy M.; Hivert, Marie-France; Felix, Janine F.; Hypponen, Elina; Lowe, William L.; Evans, David M.; Lawlor, Debbie A.; Feenstra, Bjarke; Freathy, Rachel M. 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 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 x 10(-8). 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. Oxford Oxford Univ. Press 2018 15 Human molecular genetics 27 4 742 756 10.1093/hmg/ddx429 Institut für Biochemie und Biologie OPUS4-42310 misc Beaumont, Robin N.; Warrington, Nicole M.; Cavadino, Alana; Tyrrell, Jessica; Nodzenski, Michael; Horikoshi, Momoko; Geller, Frank; Myhre, Ronny; Richmond, Rebecca C.; Paternoster, Lavinia; Bradfield, Jonathan P.; Kreiner-Møller, Eskil; Huikari, Ville; Metrustry, Sarah; Lunetta, Kathryn L.; Painter, Jodie N.; Hottenga, Jouke-Jan; Allard, Catherine; Barton, Sheila J.; Espinosa, Ana; Marsh, Julie A.; Potter, Catherine; Zhang, Ge; Ang, Wei; Berry, Diane J.; Bouchard, Luigi; Das, Shikta; Hakonarson, Hakon; Heikkinen, Jani; Helgeland, Øyvind; Hocher, Berthold; Hofman, Albert; Inskip, Hazel M.; Jones, Samuel E.; Kogevinas, Manolis; Lind, Penelope A.; Marullo, Letizia; Medland, Sarah E.; Murray, Anna; Murray, Jeffrey C.; Njølstad, Pa ̊l R.; Nohr, Ellen A.; Reichetzeder, Christoph; Ring, Susan M.; Ruth, Katherine S.; Santa-Marina, Loreto; Scholtens, Denise M.; Sebert, Sylvain; Sengpiel, Verena; Tuke, Marcus A.; Vaudel, Marc; Weedon, Michael N.; Willemsen, Gonneke; Wood, Andrew R.; Yaghootkar, Hanieh; Muglia, Louis J.; Bartels, Meike; Relton, Caroline L.; Pennell, Craig E.; Chatzi, Leda; Estivill, Xavier; Holloway, John W.; Boomsma, Dorret I.; Montgomery, Grant W.; Murabito, Joanne M.; Spector, Tim D.; Power, Christine; Ja ̈rvelin, Marjo-Ritta; Bisgaard, Hans; Grant, Struan F.A.; Sørensen, Thorkild I.A.; Jaddoe, Vincent W.; Jacobsson, Bo; Melbye, Mads; McCarthy, Mark I.; Hattersley, Andrew T.; Hayes, M. Geoffrey; Frayling, Timothy M.; Hivert, Marie-France; Felix, Janine F.; Hyppo ̈nen, Elina; Lowe, William L. , Jr; Evans, David M.; Lawlor, Debbie A.; Feenstra, Bjarke; Freathy, Rachel M. 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 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. 2017 15 Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe 628 urn:nbn:de:kobv:517-opus4-423100 10.25932/publishup-42310 Mathematisch-Naturwissenschaftliche Fakultät