@article{WarringtonBeaumontHorikoshietal.2019, author = {Warrington, Nicole and Beaumont, Robin and Horikoshi, Momoko and Day, Felix R. and Helgeland, {\O}yvind and Laurin, Charles and Bacelis, Jonas and Peng, Shouneng and Hao, Ke and Feenstra, Bjarke and Wood, Andrew R. and Mahajan, Anubha and Tyrrell, Jessica and Robertson, Neil R. and Rayner, N. William and Qiao, Zhen and Moen, Gunn-Helen and Vaudel, Marc and Marsit, Carmen and Chen, Jia and Nodzenski, Michael and Schnurr, Theresia M. and Zafarmand, Mohammad Hadi and Bradfield, Jonathan P. and Grarup, Niels and Kooijman, Marjolein N. and Li-Gao, Ruifang and Geller, Frank and Ahluwalia, Tarunveer Singh and Paternoster, Lavinia and Rueedi, Rico and Huikari, Ville and Hottenga, Jouke-Jan and Lyytik{\"a}inen, Leo-Pekka and Cavadino, Alana and Metrustry, Sarah and Cousminer, Diana L. and Wu, Ying and Thiering, Elisabeth Paula and Wang, Carol A. and Have, Christian Theil and Vilor-Tejedor, Natalia and Joshi, Peter K. and Painter, Jodie N. and Ntalla, Ioanna and Myhre, Ronny and Pitk{\"a}nen, Niina and van Leeuwen, Elisabeth M. and Joro, Raimo and Lagou, Vasiliki and Richmond, Rebecca C. and Espinosa, Ana and Barton, Sheila J. and Inskip, Hazel M. and Holloway, John W. and Santa-Marina, Loreto and Estivill, Xavier and Ang, Wei and Marsh, Julie A. and Reichetzeder, Christoph and Marullo, Letizia and Hocher, Berthold and Lunetta, Kathryn L. and Murabito, Joanne M. and Relton, Caroline L. and Kogevinas, Manolis and Chatzi, Leda and Allard, Catherine and Bouchard, Luigi and Hivert, Marie-France and Zhang, Ge and Muglia, Louis J. and Heikkinen, Jani and Morgen, Camilla S. and van Kampen, Antoine H. C. and van Schaik, Barbera D. C. and Mentch, Frank D. and Langenberg, Claudia and Scott, Robert A. and Zhao, Jing Hua and Hemani, Gibran and Ring, Susan M. and Bennett, Amanda J. and Gaulton, Kyle J. and Fernandez-Tajes, Juan and van Zuydam, Natalie R. and Medina-Gomez, Carolina and de Haan, Hugoline G. and Rosendaal, Frits R. and Kutalik, Zolt{\´a}n and Marques-Vidal, Pedro and Das, Shikta and Willemsen, Gonneke and Mbarek, Hamdi and M{\"u}ller-Nurasyid, Martina and Standl, Marie and Appel, Emil V. R. and Fonvig, Cilius Esmann and Trier, Caecilie and van Beijsterveldt, Catharina E. M. and Murcia, Mario and Bustamante, Mariona and Bon{\`a}s-Guarch, S{\´i}lvia and Hougaard, David M. and Mercader, Josep M. and Linneberg, Allan and Schraut, Katharina E. and Lind, Penelope A. and Medland, Sarah Elizabeth and Shields, Beverley M. and Knight, Bridget A. and Chai, Jin-Fang and Panoutsopoulou, Kalliope and Bartels, Meike and S{\´a}nchez, Friman and Stokholm, Jakob and Torrents, David and Vinding, Rebecca K. and Willems, Sara M. and Atalay, Mustafa and Chawes, Bo L. and Kovacs, Peter and Prokopenko, Inga and Tuke, Marcus A. and Yaghootkar, Hanieh and Ruth, Katherine S. and Jones, Samuel E. and Loh, Po-Ru and Murray, Anna and Weedon, Michael N. and T{\"o}njes, Anke and Stumvoll, Michael and Michaelsen, Kim Fleischer and Eloranta, Aino-Maija and Lakka, Timo A. and van Duijn, Cornelia M. and Kiess, Wieland and Koerner, Antje and Niinikoski, Harri and Pahkala, Katja and Raitakari, Olli T. and Jacobsson, Bo and Zeggini, Eleftheria and Dedoussis, George V. and Teo, Yik-Ying and Saw, Seang-Mei and Montgomery, Grant W. and Campbell, Harry and Wilson, James F. and Vrijkotte, Tanja G. M. and Vrijheid, Martine and de Geus, Eco J. C. N. and Hayes, M. Geoffrey and Kadarmideen, Haja N. and Holm, Jens-Christian and Beilin, Lawrence J. and Pennell, Craig E. and Heinrich, Joachim and Adair, Linda S. and Borja, Judith B. and Mohlke, Karen L. and Eriksson, Johan G. and Widen, Elisabeth E. and Hattersley, Andrew T. and Spector, Tim D. and Kaehoenen, Mika and Viikari, Jorma S. and Lehtimaeki, Terho and Boomsma, Dorret I. and Sebert, Sylvain and Vollenweider, Peter and Sorensen, Thorkild I. A. and Bisgaard, Hans and Bonnelykke, Klaus and Murray, Jeffrey C. and Melbye, Mads and Nohr, Ellen A. and Mook-Kanamori, Dennis O. and Rivadeneira, Fernando and Hofman, Albert and Felix, Janine F. and Jaddoe, Vincent W. V. and Hansen, Torben and Pisinger, Charlotta and Vaag, Allan A. and Pedersen, Oluf and Uitterlinden, Andre G. and Jarvelin, Marjo-Riitta and Power, Christine and Hypponen, Elina and Scholtens, Denise M. and Lowe, William L. and Smith, George Davey and Timpson, Nicholas J. and Morris, Andrew P. and Wareham, Nicholas J. and Hakonarson, Hakon and Grant, Struan F. A. and Frayling, Timothy M. and Lawlor, Debbie A. and Njolstad, Pal R. and Johansson, Stefan and Ong, Ken K. and McCarthy, Mark I. and Perry, John R. B. and Evans, David M. and Freathy, Rachel M.}, title = {Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors}, series = {Nature genetics}, volume = {51}, journal = {Nature genetics}, number = {5}, publisher = {Nature Publ. Group}, address = {New York}, organization = {EGG Consortium}, issn = {1061-4036}, pages = {804 -- +}, year = {2019}, abstract = {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.}, language = {en} } @article{BeaumontWarringtonCavadinoetal.2018, author = {Beaumont, Robin N. and Warrington, Nicole M. and Cavadino, Alana and Tyrrell, Jessica and Nodzenski, Michael and Horikoshi, Momoko and Geller, Frank and Myhre, Ronny and Richmond, Rebecca C. and Paternoster, Lavinia and Bradfield, Jonathan P. and Kreiner-Moller, Eskil and Huikari, Ville and Metrustry, Sarah and Lunetta, Kathryn L. and Painter, Jodie N. and Hottenga, Jouke-Jan and Allard, Catherine and Barton, Sheila J. and Espinosa, Ana and Marsh, Julie A. and Potter, Catherine and Zhang, Ge and Ang, Wei and Berry, Diane J. and Bouchard, Luigi and Das, Shikta and Hakonarson, Hakon and Heikkinen, Jani and Helgeland, Oyvind and Hocher, Berthold and Hofman, Albert and Inskip, Hazel M. and Jones, Samuel E. and Kogevinas, Manolis and Lind, Penelope A. and Marullo, Letizia and Medland, Sarah E. and Murray, Anna and Murray, Jeffrey C. and Njolstad, Pal R. and Nohr, Ellen A. and Reichetzeder, Christoph and Ring, Susan M. and Ruth, Katherine S. and Santa-Marina, Loreto and Scholtens, Denise M. and Sebert, Sylvain and Sengpiel, Verena and Tuke, Marcus A. and Vaudel, Marc and Weedon, Michael N. and Willemsen, Gonneke and Wood, Andrew R. and Yaghootkar, Hanieh and Muglia, Louis J. and Bartels, Meike and Relton, Caroline L. and Pennell, Craig E. and Chatzi, Leda and Estivill, Xavier and Holloway, John W. and Boomsma, Dorret I. and Montgomery, Grant W. and Murabito, Joanne M. and Spector, Tim D. and Power, Christine and Jarvelin, Marjo-Ritta and Bisgaard, Hans and Grant, Struan F. A. and Sorensen, Thorkild I. A. and Jaddoe, Vincent W. and Jacobsson, Bo and Melbye, Mads and McCarthy, Mark I. and Hattersley, Andrew T. and Hayes, M. Geoffrey and Frayling, Timothy M. and Hivert, Marie-France and Felix, Janine F. and Hypponen, Elina and Lowe, William L. and Evans, David M. and Lawlor, Debbie A. and Feenstra, Bjarke and Freathy, Rachel M.}, title = {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}, series = {Human molecular genetics}, volume = {27}, journal = {Human molecular genetics}, number = {4}, publisher = {Oxford Univ. Press}, address = {Oxford}, organization = {Early Growth Genetics EGG}, issn = {0964-6906}, doi = {10.1093/hmg/ddx429}, pages = {742 -- 756}, year = {2018}, abstract = {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.}, language = {en} } @article{vanderValkKreinerMollerKooijmanetal.2015, author = {van der Valk, Ralf J. P. and Kreiner-Moller, Eskil and Kooijman, Marjolein N. and Guxens, Monica and Stergiakouli, Evangelia and Saaf, Annika and Bradfield, Jonathan P. and Geller, Frank and Hayes, M. Geoffrey and Cousminer, Diana L. and Koerner, Antje and Thiering, Elisabeth and Curtin, John A. and Myhre, Ronny and Huikari, Ville and Joro, Raimo and Kerkhof, Marjan and Warrington, Nicole M. and Pitkanen, Niina and Ntalla, Ioanna and Horikoshi, Momoko and Veijola, Riitta and Freathy, Rachel M. and Teo, Yik-Ying and Barton, Sheila J. and Evans, David M. and Kemp, John P. and St Pourcain, Beate and Ring, Susan M. and Smith, George Davey and Bergstrom, Anna and Kull, Inger and Hakonarson, Hakon and Mentch, Frank D. and Bisgaard, Hans and Chawes, Bo Lund Krogsgaard and Stokholm, Jakob and Waage, Johannes and Eriksen, Patrick and Sevelsted, Astrid and Melbye, Mads and van Duijn, Cornelia M. and Medina-Gomez, Carolina and Hofman, Albert and de Jongste, Johan C. and Taal, H. Rob and Uitterlinden, Andre G. and Armstrong, Loren L. and Eriksson, Johan and Palotie, Aarno and Bustamante, Mariona and Estivill, Xavier and Gonzalez, Juan R. and Llop, Sabrina and Kiess, Wieland and Mahajan, Anubha and Flexeder, Claudia and Tiesler, Carla M. T. and Murray, Clare S. and Simpson, Angela and Magnus, Per and Sengpiel, Verena and Hartikainen, Anna-Liisa and Keinanen-Kiukaanniemi, Sirkka and Lewin, Alexandra and Alves, Alexessander Da Silva Couto and Blakemore, Alexandra I. F. and Buxton, Jessica L. and Kaakinen, Marika and Rodriguez, Alina and Sebert, Sylvain and Vaarasmaki, Marja and Lakka, Timo and Lindi, Virpi and Gehring, Ulrike and Postma, Dirkje S. and Ang, Wei and Newnham, John P. and Lyytikainen, Leo-Pekka and Pahkala, Katja and Raitakari, Olli T. and Panoutsopoulou, Kalliope and Zeggini, Eleftheria and Boomsma, Dorret I. and Groen-Blokhuis, Maria and Ilonen, Jorma and Franke, Lude and Hirschhorn, Joel N. and Pers, Tune H. and Liang, Liming and Huang, Jinyan and Hocher, Berthold and Knip, Mikael and Saw, Seang-Mei and Holloway, John W. and Melen, Erik and Grant, Struan F. A. and Feenstra, Bjarke and Lowe, William L. and Widen, Elisabeth and Sergeyev, Elena and Grallert, Harald and Custovic, Adnan and Jacobsson, Bo and Jarvelin, Marjo-Riitta and Atalay, Mustafa and Koppelman, Gerard H. and Pennell, Craig E. and Niinikoski, Harri and Dedoussis, George V. and Mccarthy, Mark I. and Frayling, Timothy M. and Sunyer, Jordi and Timpson, Nicholas J. and Rivadeneira, Fernando and Bonnelykke, Klaus and Jaddoe, Vincent W. V.}, title = {A novel common variant in DCST2 is associated with length in early life and height in adulthood}, series = {Human molecular genetics}, volume = {24}, journal = {Human molecular genetics}, number = {4}, publisher = {Oxford Univ. Press}, address = {Oxford}, organization = {Early Genetics Lifecourse, Genetic Invest ANthropometric, Early Growth Genetics EGG}, issn = {0964-6906}, doi = {10.1093/hmg/ddu510}, pages = {1155 -- 1168}, year = {2015}, abstract = {Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 x 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; beta = 0.046, SE = 0.008, P = 2.46 x 10(-8), explained variance = 0.05\%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 x 10(-4)) and adult height (N = 127 513; P = 1.45 x 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13\% of variance in birth length. The same SNPs explained 2.95\% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.}, language = {en} } @article{HorikoshiYaghootkarMookKanamorietal.2013, author = {Horikoshi, Momoko and Yaghootkar, Hanieh and Mook-Kanamori, Dennis O. and Sovio, Ulla and Taal, H. Rob and Hennig, Branwen J. and Bradfield, Jonathan P. and St Pourcain, Beate and Evans, David M. and Charoen, Pimphen and Kaakinen, Marika and Cousminer, Diana L. and Lehtimaki, Terho and Kreiner-Moller, Eskil and Warrington, Nicole M. and Bustamante, Mariona and Feenstra, Bjarke and Berry, Diane J. and Thiering, Elisabeth and Pfab, Thiemo and Barton, Sheila J. and Shields, Beverley M. and Kerkhof, Marjan and van Leeuwen, Elisabeth M. and Fulford, Anthony J. and Kutalik, Zoltan and Zhao, Jing Hua and den Hoed, Marcel and Mahajan, Anubha and Lindi, Virpi and Goh, Liang-Kee and Hottenga, Jouke-Jan and Wu, Ying and Raitakari, Olli T. and Harder, Marie N. and Meirhaeghe, Aline and Ntalla, Ioanna and Salem, Rany M. and Jameson, Karen A. and Zhou, Kaixin and Monies, Dorota M. and Lagou, Vasiliki and Kirin, Mirna and Heikkinen, Jani and Adair, Linda S. and Alkuraya, Fowzan S. and Al-Odaib, Ali and Amouyel, Philippe and Andersson, Ehm Astrid and Bennett, Amanda J. and Blakemore, Alexandra I. F. and Buxton, Jessica L. and Dallongeville, Jean and Das, Shikta and de Geus, Eco J. C. and Estivill, Xavier and Flexeder, Claudia and Froguel, Philippe and Geller, Frank and Godfrey, Keith M. and Gottrand, Frederic and Groves, Christopher J. and Hansen, Torben and Hirschhorn, Joel N. and Hofman, Albert and Hollegaard, Mads V. and Hougaard, David M. and Hyppoenen, Elina and Inskip, Hazel M. and Isaacs, Aaron and Jorgensen, Torben and Kanaka-Gantenbein, Christina and Kemp, John P. and Kiess, Wieland and Kilpelainen, Tuomas O. and Klopp, Norman and Knight, Bridget A. and Kuzawa, Christopher W. and McMahon, George and Newnham, John P. and Niinikoski, Harri and Oostra, Ben A. and Pedersen, Louise and Postma, Dirkje S. and Ring, Susan M. and Rivadeneira, Fernando and Robertson, Neil R. and Sebert, Sylvain and Simell, Olli and Slowinski, Torsten and Tiesler, Carla M. T. and Toenjes, Anke and Vaag, Allan and Viikari, Jorma S. and Vink, Jacqueline M. and Vissing, Nadja Hawwa and Wareham, Nicholas J. and Willemsen, Gonneke and Witte, Daniel R. and Zhang, Haitao and Zhao, Jianhua and Wilson, James F. and Stumvoll, Michael and Prentice, Andrew M. and Meyer, Brian F. and Pearson, Ewan R. and Boreham, Colin A. G. and Cooper, Cyrus and Gillman, Matthew W. and Dedoussis, George V. and Moreno, Luis A. and Pedersen, Oluf and Saarinen, Maiju and Mohlke, Karen L. and Boomsma, Dorret I. and Saw, Seang-Mei and Lakka, Timo A. and Koerner, Antje and Loos, Ruth J. F. and Ong, Ken K. and Vollenweider, Peter and van Duijn, Cornelia M. and Koppelman, Gerard H. and Hattersley, Andrew T. and Holloway, John W. and Hocher, Berthold and Heinrich, Joachim and Power, Chris and Melbye, Mads and Guxens, Monica and Pennell, Craig E. and Bonnelykke, Klaus and Bisgaard, Hans and Eriksson, Johan G. and Widen, Elisabeth and Hakonarson, Hakon and Uitterlinden, Andre G. and Pouta, Anneli and Lawlor, Debbie A. and Smith, George Davey and Frayling, Timothy M. and McCarthy, Mark I. and Grant, Struan F. A. and Jaddoe, Vincent W. V. and Jarvelin, Marjo-Riitta and Timpson, Nicholas J. and Prokopenko, Inga and Freathy, Rachel M.}, title = {New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism}, series = {Nature genetics}, volume = {45}, journal = {Nature genetics}, number = {1}, publisher = {Nature Publ. Group}, address = {New York}, organization = {MAGIC, Early Growth Genetics EGG}, issn = {1061-4036}, doi = {10.1038/ng.2477}, pages = {76 -- U115}, year = {2013}, abstract = {Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.}, language = {en} }