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- Adar formation (1)
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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.
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.
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
(2019)
Middeldorp, Christel M. ; Mahajan, Anubha ; Horikoshi, Momoko ; Robertson, Neil R. ; Beaumont, Robin N. ; Bradfield, Jonathan P. ; Bustamante, Mariona ; Cousminer, Diana L. ; Day, Felix R. ; De Silva, N. Maneka ; Guxens, Monica ; Mook-Kanamori, Dennis O. ; St Pourcain, Beate ; Warrington, Nicole M. ; Adair, Linda S. ; Ahlqvist, Emma ; Ahluwalia, Tarunveer Singh ; Almgren, Peter ; Ang, Wei ; Atalay, Mustafa ; Auvinen, Juha ; Bartels, Meike ; Beckmann, Jacques S. ; Bilbao, Jose Ramon ; Bond, Tom ; Borja, Judith B. ; Cavadino, Alana ; Charoen, Pimphen ; Chen, Zhanghua ; Coin, Lachlan ; Cooper, Cyrus ; Curtin, John A. ; Custovic, Adnan ; Das, Shikta ; Davies, Gareth E. ; Dedoussis, George V. ; Duijts, Liesbeth ; Eastwood, Peter R. ; Eliasen, Anders U. ; Elliott, Paul ; Eriksson, Johan G. ; Estivill, Xavier ; Fadista, Joao ; Fedko, Iryna O. ; Frayling, Timothy M. ; Gaillard, Romy ; Gauderman, W. James ; Geller, Frank ; Gilliland, Frank ; Gilsanz, Vincente ; Granell, Raquel ; Grarup, Niels ; Groop, Leif ; Hadley, Dexter ; Hakonarson, Hakon ; Hansen, Torben ; Hartman, Catharina A. ; Hattersley, Andrew T. ; Hayes, M. Geoffrey ; Hebebrand, Johannes ; Heinrich, Joachim ; Helgeland, Oyvind ; Henders, Anjali K. ; Henderson, John ; Henriksen, Tine B. ; Hirschhorn, Joel N. ; Hivert, Marie-France ; Hocher, Berthold ; Holloway, John W. ; Holt, Patrick ; Hottenga, Jouke-Jan ; Hypponen, Elina ; Iniguez, Carmen ; Johansson, Stefan ; Jugessur, Astanand ; Kahonen, Mika ; Kalkwarf, Heidi J. ; Kaprio, Jaakko ; Karhunen, Ville ; Kemp, John P. ; Kerkhof, Marjan ; Koppelman, Gerard H. ; Korner, Antje ; Kotecha, Sailesh ; Kreiner-Moller, Eskil ; Kulohoma, Benard ; Kumar, Ashish ; Kutalik, Zoltan ; Lahti, Jari ; Lappe, Joan M. ; Larsson, Henrik ; Lehtimaki, Terho ; Lewin, Alexandra M. ; Li, Jin ; Lichtenstein, Paul ; Lindgren, Cecilia M. ; Lindi, Virpi ; Linneberg, Allan ; Liu, Xueping ; Liu, Jun ; Lowe, William L. ; Lundstrom, Sebastian ; Lyytikainen, Leo-Pekka ; Ma, Ronald C. W. ; Mace, Aurelien ; Magi, Reedik ; Magnus, Per ; Mamun, Abdullah A. ; Mannikko, Minna ; Martin, Nicholas G. ; Mbarek, Hamdi ; McCarthy, Nina S. ; Medland, Sarah E. ; Melbye, Mads ; Melen, Erik ; Mohlke, Karen L. ; Monnereau, Claire ; Morgen, Camilla S. ; Morris, Andrew P. ; Murray, Jeffrey C. ; Myhre, Ronny ; Najman, Jackob M. ; Nivard, Michel G. ; Nohr, Ellen A. ; Nolte, Ilja M. ; Ntalla, Ioanna ; Oberfield, Sharon E. ; Oken, Emily ; Oldehinkel, Albertine J. ; Pahkala, Katja ; Palviainen, Teemu ; Panoutsopoulou, Kalliope ; Pedersen, Oluf ; Pennell, Craig E. ; Pershagen, Goran ; Pitkanen, Niina ; Plomin, Robert ; Power, Christine ; Prasad, Rashmi B. ; Prokopenko, Inga ; Pulkkinen, Lea ; Raikkonen, Katri ; Raitakari, Olli T. ; Reynolds, Rebecca M. ; Richmond, Rebecca C. ; Rivadeneira, Fernando ; Rodriguez, Alina ; Rose, Richard J. ; Salem, Rany ; Santa-Marina, Loreto ; Saw, Seang-Mei ; Schnurr, Theresia M. ; Scott, James G. ; Selzam, Saskia ; Shepherd, John A. ; Simpson, Angela ; Skotte, Line ; Sleiman, Patrick M. A. ; Snieder, Harold ; Sorensen, Thorkild I. A. ; Standl, Marie ; Steegers, Eric A. P. ; Strachan, David P. ; Straker, Leon ; Strandberg, Timo ; Taylor, Michelle ; Teo, Yik-Ying ; Thiering, Elisabeth ; Torrent, Maties ; Tyrrell, Jessica ; Uitterlinden, Andre G. ; van Beijsterveldt, Toos ; van der Most, Peter J. ; van Duijn, Cornelia M. ; Viikari, Jorma ; Vilor-Tejedor, Natalia ; Vogelezang, Suzanne ; Vonk, Judith M. ; Vrijkotte, Tanja G. M. ; Vuoksimaa, Eero ; Wang, Carol A. ; Watkins, William J. ; Wichmann, H-Erich ; Willemsen, Gonneke ; Williams, Gail M. ; Wilson, James F. ; Wray, Naomi R. ; Xu, Shujing ; Xu, Cheng-Jian ; Yaghootkar, Hanieh ; Yi, Lu ; Zafarmand, Mohammad Hadi ; Zeggini, Eleftheria ; Zemel, Babette S. ; Hinney, Anke ; Lakka, Timo A. ; Whitehouse, Andrew J. O. ; Sunyer, Jordi ; Widen, Elisabeth E. ; Feenstra, Bjarke ; Sebert, Sylvain ; Jacobsson, Bo ; Njolstad, Pal R. ; Stoltenberg, Camilla ; Smith, George Davey ; Lawlor, Debbie A. ; Paternoster, Lavinia ; Timpson, Nicholas J. ; Ong, Ken K. ; Bisgaard, Hans ; Bonnelykke, Klaus ; Jaddoe, Vincent W. V. ; Tiemeier, Henning ; Jarvelin, Marjo-Riitta ; Evans, David M. ; Perry, John R. B. ; Grant, Struan F. A. ; Boomsma, Dorret I. ; Freathy, Rachel M. ; McCarthy, Mark I. ; Felix, Janine F.
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
Aarts, Alexander A. ; Anderson, Joanna E. ; Anderson, Christopher J. ; Attridge, Peter R. ; Attwood, Angela ; Axt, Jordan ; Babel, Molly ; Bahnik, Stepan ; Baranski, Erica ; Barnett-Cowan, Michael ; Bartmess, Elizabeth ; Beer, Jennifer ; Bell, Raoul ; Bentley, Heather ; Beyan, Leah ; Binion, Grace ; Borsboom, Denny ; Bosch, Annick ; Bosco, Frank A. ; Bowman, Sara D. ; Brandt, Mark J. ; Braswell, Erin ; Brohmer, Hilmar ; Brown, Benjamin T. ; Brown, Kristina ; Bruening, Jovita ; Calhoun-Sauls, Ann ; Callahan, Shannon P. ; Chagnon, Elizabeth ; Chandler, Jesse ; Chartier, Christopher R. ; Cheung, Felix ; Christopherson, Cody D. ; Cillessen, Linda ; Clay, Russ ; Cleary, Hayley ; Cloud, Mark D. ; Cohn, Michael ; Cohoon, Johanna ; Columbus, Simon ; Cordes, Andreas ; Costantini, Giulio ; Alvarez, Leslie D. Cramblet ; Cremata, Ed ; Crusius, Jan ; DeCoster, Jamie ; DeGaetano, Michelle A. ; Della Penna, Nicolas ; den Bezemer, Bobby ; Deserno, Marie K. ; Devitt, Olivia ; Dewitte, Laura ; Dobolyi, David G. ; Dodson, Geneva T. ; Donnellan, M. Brent ; Donohue, Ryan ; Dore, Rebecca A. ; Dorrough, Angela ; Dreber, Anna ; Dugas, Michelle ; Dunn, Elizabeth W. ; Easey, Kayleigh ; Eboigbe, Sylvia ; Eggleston, Casey ; Embley, Jo ; Epskamp, Sacha ; Errington, Timothy M. ; Estel, Vivien ; Farach, Frank J. ; Feather, Jenelle ; Fedor, Anna ; Fernandez-Castilla, Belen ; Fiedler, Susann ; Field, James G. ; Fitneva, Stanka A. ; Flagan, Taru ; Forest, Amanda L. ; Forsell, Eskil ; Foster, Joshua D. ; Frank, Michael C. ; Frazier, Rebecca S. ; Fuchs, Heather ; Gable, Philip ; Galak, Jeff ; Galliani, Elisa Maria ; Gampa, Anup ; Garcia, Sara ; Gazarian, Douglas ; Gilbert, Elizabeth ; Giner-Sorolla, Roger ; Glöckner, Andreas ; Göllner, Lars ; Goh, Jin X. ; Goldberg, Rebecca ; Goodbourn, Patrick T. ; Gordon-McKeon, Shauna ; Gorges, Bryan ; Gorges, Jessie ; Goss, Justin ; Graham, Jesse ; Grange, James A. ; Gray, Jeremy ; Hartgerink, Chris ; Hartshorne, Joshua ; Hasselman, Fred ; Hayes, Timothy ; Heikensten, Emma ; Henninger, Felix ; Hodsoll, John ; Holubar, Taylor ; Hoogendoorn, Gea ; Humphries, Denise J. ; Hung, Cathy O. -Y. ; Immelman, Nathali ; Irsik, Vanessa C. ; Jahn, Georg ; Jaekel, Frank ; Jekel, Marc ; Johannesson, Magnus ; Johnson, Larissa G. ; Johnson, David J. ; Johnson, Kate M. ; Johnston, William J. ; Jonas, Kai ; Joy-Gaba, Jennifer A. ; Kappes, Heather Barry ; Kelso, Kim ; Kidwell, Mallory C. ; Kim, Seung Kyung ; Kirkhart, Matthew ; Kleinberg, Bennett ; Knezevic, Goran ; Kolorz, Franziska Maria ; Kossakowski, Jolanda J. ; Krause, Robert Wilhelm ; Krijnen, Job ; Kuhlmann, Tim ; Kunkels, Yoram K. ; Kyc, Megan M. ; Lai, Calvin K. ; Laique, Aamir ; Lakens, Daniel ; Lane, Kristin A. ; Lassetter, Bethany ; Lazarevic, Ljiljana B. ; LeBel, Etienne P. ; Lee, Key Jung ; Lee, Minha ; Lemm, Kristi ; Levitan, Carmel A. ; Lewis, Melissa ; Lin, Lin ; Lin, Stephanie ; Lippold, Matthias ; Loureiro, Darren ; Luteijn, Ilse ; Mackinnon, Sean ; Mainard, Heather N. ; Marigold, Denise C. ; Martin, Daniel P. ; Martinez, Tylar ; Masicampo, E. J. ; Matacotta, Josh ; Mathur, Maya ; May, Michael ; Mechin, Nicole ; Mehta, Pranjal ; Meixner, Johannes ; Melinger, Alissa ; Miller, Jeremy K. ; Miller, Mallorie ; Moore, Katherine ; Möschl, Marcus ; Motyl, Matt ; Müller, Stephanie M. ; Munafo, Marcus ; Neijenhuijs, Koen I. ; Nervi, Taylor ; Nicolas, Gandalf ; Nilsonne, Gustav ; Nosek, Brian A. ; Nuijten, Michele B. ; Olsson, Catherine ; Osborne, Colleen ; Ostkamp, Lutz ; Pavel, Misha ; Penton-Voak, Ian S. ; Perna, Olivia ; Pernet, Cyril ; Perugini, Marco ; Pipitone, R. Nathan ; Pitts, Michael ; Plessow, Franziska ; Prenoveau, Jason M. ; Rahal, Rima-Maria ; Ratliff, Kate A. ; Reinhard, David ; Renkewitz, Frank ; Ricker, Ashley A. ; Rigney, Anastasia ; Rivers, Andrew M. ; Roebke, Mark ; Rutchick, Abraham M. ; Ryan, Robert S. ; Sahin, Onur ; Saide, Anondah ; Sandstrom, Gillian M. ; Santos, David ; Saxe, Rebecca ; Schlegelmilch, Rene ; Schmidt, Kathleen ; Scholz, Sabine ; Seibel, Larissa ; Selterman, Dylan Faulkner ; Shaki, Samuel ; Simpson, William B. ; Sinclair, H. Colleen ; Skorinko, Jeanine L. M. ; Slowik, Agnieszka ; Snyder, Joel S. ; Soderberg, Courtney ; Sonnleitner, Carina ; Spencer, Nick ; Spies, Jeffrey R. ; Steegen, Sara ; Stieger, Stefan ; Strohminger, Nina ; Sullivan, Gavin B. ; Talhelm, Thomas ; Tapia, Megan ; te Dorsthorst, Anniek ; Thomae, Manuela ; Thomas, Sarah L. ; Tio, Pia ; Traets, Frits ; Tsang, Steve ; Tuerlinckx, Francis ; Turchan, Paul ; Valasek, Milan ; Van Aert, Robbie ; van Assen, Marcel ; van Bork, Riet ; van de Ven, Mathijs ; van den Bergh, Don ; van der Hulst, Marije ; van Dooren, Roel ; van Doorn, Johnny ; van Renswoude, Daan R. ; van Rijn, Hedderik ; Vanpaemel, Wolf ; Echeverria, Alejandro Vasquez ; Vazquez, Melissa ; Velez, Natalia ; Vermue, Marieke ; Verschoor, Mark ; Vianello, Michelangelo ; Voracek, Martin ; Vuu, Gina ; Wagenmakers, Eric-Jan ; Weerdmeester, Joanneke ; Welsh, Ashlee ; Westgate, Erin C. ; Wissink, Joeri ; Wood, Michael ; Woods, Andy ; Wright, Emily ; Wu, Sining ; Zeelenberg, Marcel ; Zuni, Kellylynn
Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
A novel common variant in DCST2 is associated with length in early life and height in adulthood
(2015)
van der Valk, Ralf J. P. ; Kreiner-Moller, Eskil ; Kooijman, Marjolein N. ; Guxens, Monica ; Stergiakouli, Evangelia ; Saaf, Annika ; Bradfield, Jonathan P. ; Geller, Frank ; Hayes, M. Geoffrey ; Cousminer, Diana L. ; Koerner, Antje ; Thiering, Elisabeth ; Curtin, John A. ; Myhre, Ronny ; Huikari, Ville ; Joro, Raimo ; Kerkhof, Marjan ; Warrington, Nicole M. ; Pitkanen, Niina ; Ntalla, Ioanna ; Horikoshi, Momoko ; Veijola, Riitta ; Freathy, Rachel M. ; Teo, Yik-Ying ; Barton, Sheila J. ; Evans, David M. ; Kemp, John P. ; St Pourcain, Beate ; Ring, Susan M. ; Smith, George Davey ; Bergstrom, Anna ; Kull, Inger ; Hakonarson, Hakon ; Mentch, Frank D. ; Bisgaard, Hans ; Chawes, Bo Lund Krogsgaard ; Stokholm, Jakob ; Waage, Johannes ; Eriksen, Patrick ; Sevelsted, Astrid ; Melbye, Mads ; van Duijn, Cornelia M. ; Medina-Gomez, Carolina ; Hofman, Albert ; de Jongste, Johan C. ; Taal, H. Rob ; Uitterlinden, Andre G. ; Armstrong, Loren L. ; Eriksson, Johan ; Palotie, Aarno ; Bustamante, Mariona ; Estivill, Xavier ; Gonzalez, Juan R. ; Llop, Sabrina ; Kiess, Wieland ; Mahajan, Anubha ; Flexeder, Claudia ; Tiesler, Carla M. T. ; Murray, Clare S. ; Simpson, Angela ; Magnus, Per ; Sengpiel, Verena ; Hartikainen, Anna-Liisa ; Keinanen-Kiukaanniemi, Sirkka ; Lewin, Alexandra ; Alves, Alexessander Da Silva Couto ; Blakemore, Alexandra I. F. ; Buxton, Jessica L. ; Kaakinen, Marika ; Rodriguez, Alina ; Sebert, Sylvain ; Vaarasmaki, Marja ; Lakka, Timo ; Lindi, Virpi ; Gehring, Ulrike ; Postma, Dirkje S. ; Ang, Wei ; Newnham, John P. ; Lyytikainen, Leo-Pekka ; Pahkala, Katja ; Raitakari, Olli T. ; Panoutsopoulou, Kalliope ; Zeggini, Eleftheria ; Boomsma, Dorret I. ; Groen-Blokhuis, Maria ; Ilonen, Jorma ; Franke, Lude ; Hirschhorn, Joel N. ; Pers, Tune H. ; Liang, Liming ; Huang, Jinyan ; Hocher, Berthold ; Knip, Mikael ; Saw, Seang-Mei ; Holloway, John W. ; Melen, Erik ; Grant, Struan F. A. ; Feenstra, Bjarke ; Lowe, William L. ; Widen, Elisabeth ; Sergeyev, Elena ; Grallert, Harald ; Custovic, Adnan ; Jacobsson, Bo ; Jarvelin, Marjo-Riitta ; Atalay, Mustafa ; Koppelman, Gerard H. ; Pennell, Craig E. ; Niinikoski, Harri ; Dedoussis, George V. ; Mccarthy, Mark I. ; Frayling, Timothy M. ; Sunyer, Jordi ; Timpson, Nicholas J. ; Rivadeneira, Fernando ; Bonnelykke, Klaus ; Jaddoe, Vincent W. V.
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.
Buratti, Bonnie J. ; Thomas, P. C. ; Roussos, Elias ; Howett, Carly ; Seiss, Martin ; Hendrix, A. R. ; Helfenstein, Paul ; Brown, R. H. ; Clark, R. N. ; Denk, Tilmann ; Filacchione, Gianrico ; Hoffmann, Holger ; Jones, Geraint H. ; Khawaja, N. ; Kollmann, Peter ; Krupp, Norbert ; Lunine, Jonathan ; Momary, T. W. ; Paranicas, Christopher ; Postberg, Frank ; Sachse, Manuel ; Spahn, Frank ; Spencer, John ; Srama, Ralf ; Albin, T. ; Baines, K. H. ; Ciarniello, Mauro ; Economou, Thanasis ; Hsu, Hsiang-Wen ; Kempf, Sascha ; Krimigis, Stamatios M. ; Mitchell, Donald ; Moragas-Klostermeyer, Georg ; Nicholson, Philip D. ; Porco, C. C. ; Rosenberg, Heike ; Simolka, Jonas ; Soderblom, Laurence A.
Saturn’s main ring system is associated with a set of small moons that either are embedded within it or interact with the rings to alter their shape and composition. Five close flybys of the moons Pan, Daphnis, Atlas, Pandora, and Epimetheus were performed between December 2016 and April 2017 during the ring-grazing orbits of the Cassini mission. Data on the moons’ morphology, structure, particle environment, and composition were returned, along with images in the ultraviolet and thermal infrared. We find that the optical properties of the moons’ surfaces are determined by two competing processes: contamination by a red material formed in Saturn’s main ring system and accretion of bright icy particles or water vapor from volcanic plumes originating on the moon Enceladus.
Arridge, Christopher S. ; Achilleos, N. ; Agarwal, Jessica ; Agnor, C. B. ; Ambrosi, R. ; Andre, N. ; Badman, S. V. ; Baines, K. ; Banfield, D. ; Barthelemy, M. ; Bisi, M. M. ; Blum, J. ; Bocanegra-Bahamon, T. ; Bonfond, B. ; Bracken, C. ; Brandt, P. ; Briand, C. ; Briois, C. ; Brooks, S. ; Castillo-Rogez, J. ; Cavalie, T. ; Christophe, B. ; Coates, Andrew J. ; Collinson, G. ; Cooper, John F. ; Costa-Sitja, M. ; Courtin, R. ; Daglis, I. A. ; De Pater, Imke ; Desai, M. ; Dirkx, D. ; Dougherty, M. K. ; Ebert, R. W. ; Filacchione, Gianrico ; Fletcher, Leigh N. ; Fortney, J. ; Gerth, I. ; Grassi, D. ; Grodent, D. ; Grün, Eberhard ; Gustin, J. ; Hedman, M. ; Helled, R. ; Henri, P. ; Hess, Sebastien ; Hillier, J. K. ; Hofstadter, M. H. ; Holme, R. ; Horanyi, M. ; Hospodarsky, George B. ; Hsu, S. ; Irwin, P. ; Jackman, C. M. ; Karatekin, O. ; Kempf, Sascha ; Khalisi, E. ; Konstantinidis, K. ; Kruger, H. ; Kurth, William S. ; Labrianidis, C. ; Lainey, V. ; Lamy, L. L. ; Laneuville, Matthieu ; Lucchesi, D. ; Luntzer, A. ; MacArthur, J. ; Maier, A. ; Masters, A. ; McKenna-Lawlor, S. ; Melin, H. ; Milillo, A. ; Moragas-Klostermeyer, Georg ; Morschhauser, Achim ; Moses, J. I. ; Mousis, O. ; Nettelmann, N. ; Neubauer, F. M. ; Nordheim, T. ; Noyelles, B. ; Orton, G. S. ; Owens, Mathew ; Peron, R. ; Plainaki, C. ; Postberg, F. ; Rambaux, N. ; Retherford, K. ; Reynaud, Serge ; Roussos, Elias ; Russell, C. T. ; Rymer, Am. ; Sallantin, R. ; Sanchez-Lavega, A. ; Santolik, O. ; Saur, J. ; Sayanagi, Km. ; Schenk, P. ; Schubert, J. ; Sergis, N. ; Sittler, E. C. ; Smith, A. ; Spahn, Frank ; Srama, Ralf ; Stallard, T. ; Sterken, V. ; Sternovsky, Zoltan ; Tiscareno, M. ; Tobie, G. ; Tosi, F. ; Trieloff, M. ; Turrini, D. ; Turtle, E. P. ; Vinatier, S. ; Wilson, R. ; Zarkat, P.
Giant planets helped to shape the conditions we see in the Solar System today and they account for more than 99% of the mass of the Sun's planetary system. They can be subdivided into the Ice Giants (Uranus and Neptune) and the Gas Giants (Jupiter and Saturn), which differ from each other in a number of fundamental ways. Uranus, in particular is the most challenging to our understanding of planetary formation and evolution, with its large obliquity, low self-luminosity, highly asymmetrical internal field, and puzzling internal structure. Uranus also has a rich planetary system consisting of a system of inner natural satellites and complex ring system, five major natural icy satellites, a system of irregular moons with varied dynamical histories, and a highly asymmetrical magnetosphere. Voyager 2 is the only spacecraft to have explored Uranus, with a flyby in 1986, and no mission is currently planned to this enigmatic system. However, a mission to the uranian system would open a new window on the origin and evolution of the Solar System and would provide crucial information on a wide variety of physicochemical processes in our Solar System. These have clear implications for understanding exoplanetary systems. In this paper we describe the science case for an orbital mission to Uranus with an atmospheric entry probe to sample the composition and atmospheric physics in Uranus' atmosphere. The characteristics of such an orbiter and a strawman scientific payload are described and we discuss the technical challenges for such a mission. This paper is based on a white paper submitted to the European Space Agency's call for science themes for its large-class mission programme in 2013.
Abdalla, Hassan E. ; Abramowski, Attila ; Aharonian, Felix A. ; Benkhali, Faiçal Ait ; Akhperjanian, A. G. ; Angüner, Ekrem Oǧuzhan ; Arrieta, M. ; Aubert, Pierre ; Backes, Michael ; Balzer, Arnim ; Barnard, Michelle ; Becherini, Yvonne ; Tjus, Julia Becker ; Berge, David ; Bernhard, Sabrina ; Bernlöhr, K. ; Birsin, E. ; Blackwell, R. ; Bottcher, Markus ; Boisson, Catherine ; Bolmont, J. ; Bordas, Pol ; Bregeon, Johan ; Brun, Francois ; Brun, Pierre ; Bryan, Mark ; Bulik, Tomasz ; Capasso, M. ; Carr, John ; Casanova, Sabrina ; Chakraborty, N. ; Chalme-Calvet, R. ; Chaves, Ryan C. G. ; Chen, Andrew ; Chevalier, J. ; Chretien, M. ; Colafrancesco, Sergio ; Cologna, Gabriele ; Condon, B. ; Conrad, Jan ; Couturier, C. ; Cui, Y. ; Davids, I. D. ; Degrange, B. ; Deil, Christoph ; deWilt, P. ; Djannati-Atai, Arache ; Domainko, Wilfried ; Donath, Axel ; Dubus, Guillaume ; Dutson, Kate ; Dyks, J. ; Dyrda, M. ; Edwards, T. ; Egberts, Kathrin ; Eger, P. ; Ernenwein, J. -P. ; Eschbach, S. ; Farnier, C. ; Fegan, Stuart ; Fernandes, M. V. ; Fiasson, A. ; Fontaine, G. ; Foerster, A. ; Funk, S. ; Füßling, Matthias ; Gabici, Stefano ; Gajdus, M. ; Gallant, Y. A. ; Garrigoux, T. ; Giavitto, Gianluca ; Giebels, B. ; Glicenstein, J. F. ; Gottschall, Daniel ; Goyal, A. ; Grondin, M. -H. ; Grudzinska, M. ; Hadasch, Daniela ; Hahn, J. ; Hawkes, J. ; Heinzelmann, G. ; Henri, Gilles ; Hermann, G. ; Hervet, Olivier ; Hillert, A. ; Hinton, James Anthony ; Hofmann, Werner ; Hoischen, Clemens ; Holler, M. ; Horns, D. ; Ivascenko, Alex ; Jacholkowska, A. ; Jamrozy, Marek ; Janiak, M. ; Jankowsky, D. ; Jankowsky, Felix ; Jingo, M. ; Jogler, Tobias ; Jouvin, Lea ; Jung-Richardt, Ira ; Kastendieck, M. A. ; Katarzynski, Krzysztof ; Katz, Uli ; Kerszberg, D. ; Khelifi, B. ; Kieffer, M. ; King, J. ; Klepser, S. ; Klochkov, Dmitry ; Kluzniak, W. ; Kolitzus, D. ; Komin, Nu. ; Kosack, K. ; Krakau, S. ; Kraus, Michael ; Krayzel, F. ; Kruger, P. P. ; Laffon, H. ; Lamanna, G. ; Lau, Jeanie ; Lees, J. -P. ; Lefaucheur, J. ; Lefranc, V. ; Lemiere, A. ; Lemoine-Goumard, M. ; Lenain, J. -P. ; Leser, Eva ; Lohse, Thomas ; Lorentz, M. ; Lui, R. ; Lypova, Iryna ; Marandon, Vincent ; Marcowith, Alexandre ; Mariaud, C. ; Marx, R. ; Maurin, G. ; Maxted, N. ; Mayer, Michael ; Meintjes, Petrus Johannes ; Menzler, U. ; Meyer, Manuel ; Mitchell, A. M. W. ; Moderski, R. ; Mohamed, M. ; Mora, K. ; Moulin, Emmanuel ; Murach, T. ; de Naurois, Mathieu ; Niederwanger, F. ; Niemiec, J. ; Oakes, L. ; Odaka, Hirokazu ; Ohm, Stefan ; Oettl, S. ; Ostrowski, M. ; Oya, I. ; Padovani, Marco ; Panter, M. ; Parsons, R. D. ; Arribas, M. Paz ; Pekeur, N. W. ; Pelletier, G. ; Petrucci, P. -O. ; Peyaud, B. ; Pita, S. ; Poon, Helen ; Prokhorov, Dmitry ; Prokoph, Heike ; Puehlhofer, Gerd ; Punch, Michael ; Quirrenbach, Andreas ; Raab, S. ; Reimer, Anita ; Reimer, Olaf ; Renaud, M. ; de los Reyes, R. ; Rieger, Frank ; Romoli, Carlo ; Rosier-Lees, S. ; Rowell, G. ; Rudak, B. ; Rulten, C. B. ; Sahakian, V. ; Salek, David ; Sanchez, David A. ; Santangelo, Andrea ; Sasaki, Manami ; Schlickeiser, Reinhard ; Schussler, F. ; Schulz, Andreas ; Schwanke, U. ; Schwemmer, S. ; Seyffert, A. S. ; Shafi, N. ; Simoni, R. ; Sol, H. ; Spanier, Felix ; Spengler, G. ; Spiess, F. ; Stawarz, Lukasz ; Steenkamp, R. ; Stegmann, Christian ; Stinzing, F. ; Stycz, K. ; Sushch, Iurii ; Tavernet, J. -P. ; Tavernier, T. ; Taylor, A. M. ; Terrier, R. ; Tluczykont, Martin ; Trichard, C. ; Tuffs, R. ; van der Walt, Johan ; van Eldik, Christopher ; van Soelen, Brian ; Vasileiadis, Georges ; Veh, J. ; Venter, C. ; Viana, A. ; Vincent, P. ; Vink, Jacco ; Voisin, F. ; Voelk, Heinrich J. ; Vuillaume, Thomas ; Wadiasingh, Z. ; Wagner, Stefan J. ; Wagner, P. ; Wagner, R. M. ; White, R. ; Wierzcholska, Alicja ; Willmann, P. ; Woernlein, A. ; Wouters, Denis ; Yang, R. ; Zabalza, Victor ; Zaborov, D. ; Zacharias, M. ; Zdziarski, A. A. ; Zech, Andreas ; Zefi, F. ; Ziegler, A. ; Zywucka, Natalia
The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using gamma-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant gamma-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section <sigma nu >. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach <sigma nu > values of 6 x 10(-26) cm(3) s(-1) in the W+W- channel for a DM particle mass of 1.5 TeV, and 2 x 10(-26) cm(3) s(-1) in the tau(+)tau(-) channel for a 1 TeV mass. For the first time, ground-based gamma-ray observations have reached sufficient sensitivity to probe <sigma nu > values expected from the thermal relic density for TeV DM particles.
Taal, H. Rob ; St Pourcain, Beate ; Thiering, Elisabeth ; Das, Shikta ; Mook-Kanamori, Dennis O. ; Warrington, Nicole M. ; Kaakinen, Marika ; Kreiner-Moller, Eskil ; Bradfield, Jonathan P. ; Freathy, Rachel M. ; Geller, Frank ; Guxens, Monica ; Cousminer, Diana L. ; Kerkhof, Marjan ; Timpson, Nicholas J. ; Ikram, M. Arfan ; Beilin, Lawrence J. ; Bonnelykke, Klaus ; Buxton, Jessica L. ; Charoen, Pimphen ; Chawes, Bo Lund Krogsgaard ; Eriksson, Johan ; Evans, David M. ; Hofman, Albert ; Kemp, John P. ; Kim, Cecilia E. ; Klopp, Norman ; Lahti, Jari ; Lye, Stephen J. ; McMahon, George ; Mentch, Frank D. ; Mueller-Nurasyid, Martina ; O'Reilly, Paul F. ; Prokopenko, Inga ; Rivadeneira, Fernando ; Steegers, Eric A. P. ; Sunyer, Jordi ; Tiesler, Carla ; Yaghootkar, Hanieh ; Breteler, Monique M. B. ; Debette, Stephanie ; Fornage, Myriam ; Gudnason, Vilmundur ; Launer, Lenore J. ; van der Lugt, Aad ; Mosley, Thomas H. ; Seshadri, Sudha ; Smith, Albert V. ; Vernooij, Meike W. ; Blakemore, Alexandra I. F. ; Chiavacci, Rosetta M. ; Feenstra, Bjarke ; Fernandez-Banet, Julio ; Grant, Struan F. A. ; Hartikainen, Anna-Liisa ; van der Heijden, Albert J. ; Iniguez, Carmen ; Lathrop, Mark ; McArdle, Wendy L. ; Molgaard, Anne ; Newnham, John P. ; Palmer, Lyle J. ; Palotie, Aarno ; Pouta, Annneli ; Ring, Susan M. ; Sovio, Ulla ; Standl, Marie ; Uitterlinden, Andre G. ; Wichmann, H-Erich ; Vissing, Nadja Hawwa ; DeCarli, Charles ; van Duijn, Cornelia M. ; McCarthy, Mark I. ; Koppelman, Gerard H. ; Estivill, Xavier ; Hattersley, Andrew T. ; Melbye, Mads ; Bisgaard, Hans ; Pennell, Craig E. ; Widen, Elisabeth ; Hakonarson, Hakon ; Smith, George Davey ; Heinrich, Joachim ; Jarvelin, Marjo-Riitta ; Jaddoe, Vincent W. V. ; Adair, Linda S. ; Ang, Wei ; Atalay, Mustafa ; van Beijsterveldt, Toos ; Bergen, Nienke ; Benke, Kelly ; Berry, Diane J. ; Bradfield, Jonathan P. ; Charoen, Pimphen ; Coin, Lachlan ; Cousminer, Diana L. ; Das, Shikta ; Davis, Oliver S. P. ; Elliott, Paul ; Evans, David M. ; Feenstra, Bjarke ; Flexeder, Claudia ; Frayling, Tim ; Freathy, Rachel M. ; Gaillard, Romy ; Geller, Frank ; Groen-Blokhuis, Maria ; Goh, Liang-Kee ; Guxens, Monica ; Haworth, Claire M. A. ; Hadley, Dexter ; Hebebrand, Johannes ; Hinney, Anke ; Hirschhorn, Joel N. ; Holloway, John W. ; Holst, Claus ; Hottenga, Jouke Jan ; Horikoshi, Momoko ; Huikari, Ville ; Hypponen, Elina ; Iniguez, Carmen ; Kaakinen, Marika ; Kilpelainen, Tuomas O. ; Kirin, Mirna ; Kowgier, Matthew ; Lakka, Hanna-Maaria ; Lange, Leslie A. ; Lawlor, Debbie A. ; Lehtimaki, Terho ; Lewin, Alex ; Lindgren, Cecilia ; Lindi, Virpi ; Maggi, Reedik ; Marsh, Julie ; Middeldorp, Christel ; Millwood, Iona ; Mook-Kanamori, Dennis O. ; Murray, Jeffrey C. ; Nivard, Michel ; Nohr, Ellen Aagaard ; Ntalla, Ioanna ; Oken, Emily ; O'Reilly, Paul F. ; Palmer, Lyle J. ; Panoutsopoulou, Kalliope ; Pararajasingham, Jennifer ; Prokopenko, Inga ; Rodriguez, Alina ; Salem, Rany M. ; Sebert, Sylvain ; Siitonen, Niina ; Sovio, Ulla ; St Pourcain, Beate ; Strachan, David P. ; Sunyer, Jordi ; Taal, H. Rob ; Teo, Yik-Ying ; Thiering, Elisabeth ; Tiesler, Carla ; Uitterlinden, Andre G. ; Valcarcel, Beatriz ; Warrington, Nicole M. ; White, Scott ; Willemsen, Gonneke ; Yaghootkar, Hanieh ; Zeggini, Eleftheria ; Boomsma, Dorret I. ; Cooper, Cyrus ; Estivill, Xavier ; Gillman, Matthew ; Grant, Struan F. A. ; Hakonarson, Hakon ; Hattersley, Andrew T. ; Heinrich, Joachim ; Hocher, Berthold ; Jaddoe, Vincent W. V. ; Jarvelin, Marjo-Riitta ; Lakka, Timo A. ; McCarthy, Mark I. ; Melbye, Mads ; Mohlke, Karen L. ; Dedoussis, George V. ; Ong, Ken K. ; Pearson, Ewan R. ; Pennell, Craig E. ; Price, Thomas S. ; Power, Chris ; Raitakari, Olli T. ; Saw, Seang-Mei ; Scherag, Andre ; Simell, Olli ; Sorensen, Thorkild I. A. ; Timpson, Nicholas J. ; Widen, Elisabeth ; Wilson, James F. ; Ang, Wei ; van Beijsterveldt, Toos ; Bergen, Nienke ; Benke, Kelly ; Berry, Diane J. ; Bradfield, Jonathan P. ; Charoen, Pimphen ; Coin, Lachlan ; Cousminer, Diana L. ; Das, Shikta ; Elliott, Paul ; Evans, David M. ; Frayling, Tim ; Freathy, Rachel M. ; Gaillard, Romy ; Groen-Blokhuis, Maria ; Guxens, Monica ; Hadley, Dexter ; Hottenga, Jouke Jan ; Huikari, Ville ; Hypponen, Elina ; Kaakinen, Marika ; Kowgier, Matthew ; Lawlor, Debbie A. ; Lewin, Alex ; Lindgren, Cecilia ; Marsh, Julie ; Middeldorp, Christel ; Millwood, Iona ; Mook-Kanamori, Dennis O. ; Nivard, Michel ; O'Reilly, Paul F. ; Palmer, Lyle J. ; Prokopenko, Inga ; Rodriguez, Alina ; Sebert, Sylvain ; Sovio, Ulla ; St Pourcain, Beate ; Standl, Marie ; Strachan, David P. ; Sunyer, Jordi ; Taal, H. Rob ; Thiering, Elisabeth ; Tiesler, Carla ; Uitterlinden, Andre G. ; Valcarcel, Beatriz ; Warrington, Nicole M. ; White, Scott ; Willemsen, Gonneke ; Yaghootkar, Hanieh ; Boomsma, Dorret I. ; Estivill, Xavier ; Grant, Struan F. A. ; Hakonarson, Hakon ; Hattersley, Andrew T. ; Heinrich, Joachim ; Jaddoe, Vincent W. V. ; Jarvelin, Marjo-Riitta ; McCarthy, Mark I. ; Pennell, Craig E. ; Power, Chris ; Timpson, Nicholas J. ; Widen, Elisabeth ; Ikram, M. Arfan ; Fornage, Myriam ; Smith, Albert V. ; Seshadri, Sudha ; Schmidt, Reinhold ; Debette, Stephanie ; Vrooman, Henri A. ; Sigurdsson, Sigurdur ; Ropele, Stefan ; Coker, Laura H. ; Longstreth, W. T. ; Niessen, Wiro J. ; DeStefano, Anita L. ; Beiser, Alexa ; Zijdenbos, Alex P. ; Struchalin, Maksim ; Jack, Clifford R. ; Nalls, Mike A. ; Au, Rhoda ; Hofman, Albert ; Gudnason, Haukur ; van der Lugt, Aad ; Harris, Tamara B. ; Meeks, William M. ; Vernooij, Meike W. ; van Buchem, Mark A. ; Catellier, Diane ; Gudnason, Vilmundur ; Windham, B. Gwen ; Wolf, Philip A. ; van Duijn, Cornelia M. ; Mosley, Thomas H. ; Schmidt, Helena ; Launer, Lenore J. ; Breteler, Monique M. B. ; DeCarli, Charles
To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
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 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.
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 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.