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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.
Brodeur, Abel ; Mikola, Derek ; Cook, Nikolai ; Brailey, Thomas ; Briggs, Ryan ; Gendre, Alexandra de ; Dupraz, Yannick ; Fiala, Lenka ; Gabani, Jacopo ; Gauriot, Romain ; Haddad, Joanne ; Lima, Goncalo ; Ankel-Peters, Jörg ; Dreber, Anna ; Campbell, Douglas ; Kattan, Lamis ; Fages, Diego Marino ; Mierisch, Fabian ; Sun, Pu ; Wright, Taylor ; Connolly, Marie ; Hoces de la Guardia, Fernando ; Johannesson, Magnus ; Miguel, Edward ; Vilhuber, Lars ; Abarca, Alejandro ; Acharya, Mahesh ; Adjisse, Sossou Simplice ; Akhtar, Ahwaz ; Lizardi, Eduardo Alberto Ramirez ; Albrecht, Sabina ; Andersen, Synve Nygaard ; Andlib, Zubaria ; Arrora, Falak ; Ash, Thomas ; Bacher, Etienne ; Bachler, Sebastian ; Bacon, Félix ; Bagues, Manuel ; Balogh, Timea ; Batmanov, Alisher ; Barschkett, Mara ; Basdil, B. Kaan ; Dower, Jaromneda ; Castek, Ondrej ; Caviglia-Harris, Jill ; Strand, Gabriella Chauca ; Chen, Shi ; Chzhen, Asya ; Chung, Jong ; Collins, Jason ; Coppock, Alexander ; Cordeau, Hugo ; Couillard, Ben ; Crechet, Jonathan ; Crippa, Lorenzo ; Cui, Jeanne ; Czymara, Christian ; Daarstad, Haley ; Dao, Danh Chi ; Dao, Dong ; Schmandt, Marco David ; Linde, Astrid de ; Melo, Lucas De ; Deer, Lachlan ; Vera, Micole De ; Dimitrova, Velichka ; Dollbaum, Jan Fabian ; Dollbaum, Jan Matti ; Donnelly, Michael ; Huynh, Luu Duc Toan ; Dumbalska, Tsvetomira ; Duncan, Jamie ; Duong, Kiet Tuan ; Duprey, Thibaut ; Dworschak, Christoph ; Ellingsrud, Sigmund ; Elminejad, Ali ; Eissa, Yasmine ; Erhart, Andrea ; Etingin-Frati, Giulian ; Fatemi-Pour, Elaheh ; Federice, Alexa ; Feld, Jan ; Fenig, Guidon ; Firouzjaeiangalougah, Mojtaba ; Fleisje, Erlend ; Fortier-Chouinard, Alexandre ; Engel, Julia Francesca ; Fries, Tilman ; Fortier, Reid ; Fréchet, Nadjim ; Galipeau, Thomas ; Gallegos, Sebastián ; Gangji, Areez ; Gao, Xiaoying ; Garnache, Cloé ; Gáspár, Attila ; Gavrilova, Evelina ; Ghosh, Arijit ; Gibney, Garreth ; Gibson, Grant ; Godager, Geir ; Goff, Leonard ; Gong, Da ; González, Javier ; Gretton, Jeremy ; Griffa, Cristina ; Grigoryeva, Idaliya ; Grtting, Maja ; Guntermann, Eric ; Guo, Jiaqi ; Gugushvili, Alexi ; Habibnia, Hooman ; Häffner, Sonja ; Hall, Jonathan D. ; Hammar, Olle ; Kordt, Amund Hanson ; Hashimoto, Barry ; Hartley, Jonathan S. ; Hausladen, Carina I. ; Havránek, Tomáš ; Hazen, Jacob ; He, Harry ; Hepplewhite, Matthew ; Herrera-Rodriguez, Mario ; Heuer, Felix ; Heyes, Anthony ; Ho, Anson T. Y. ; Holmes, Jonathan ; Holzknecht, Armando ; Hsu, Yu-Hsiang Dexter ; Hu, Shiang-Hung ; Huang, Yu-Shiuan ; Huebener, Mathias ; Huber, Christoph ; Huynh, Kim P. ; Irsova, Zuzana ; Isler, Ozan ; Jakobsson, Niklas ; Frith, Michael James ; Jananji, Raphaël ; Jayalath, Tharaka A. ; Jetter, Michael ; John, Jenny ; Forshaw, Rachel Joy ; Juan, Felipe ; Kadriu, Valon ; Karim, Sunny ; Kelly, Edmund ; Dang, Duy Khanh Hoang ; Khushboo, Tazia ; Kim, Jin ; Kjellsson, Gustav ; Kjelsrud, Anders ; Kotsadam, Andreas ; Korpershoek, Jori ; Krashinsky, Lewis ; Kundu, Suranjana ; Kustov, Alexander ; Lalayev, Nurlan ; Langlois, Audrée ; Laufer, Jill ; Lee-Whiting, Blake ; Leibing, Andreas ; Lenz, Gabriel ; Levin, Joel ; Li, Peng ; Li, Tongzhe ; Lin, Yuchen ; Listo, Ariel ; Liu, Dan ; Lu, Xuewen ; Lukmanova, Elvina ; Luscombe, Alex ; Lusher, Lester R. ; Lyu, Ke ; Ma, Hai ; Mäder, Nicolas ; Makate, Clifton ; Malmberg, Alice ; Maitra, Adit ; Mandas, Marco ; Marcus, Jan ; Margaryan, Shushanik ; Márk, Lili ; Martignano, Andres ; Marsh, Abigail ; Masetto, Isabella ; McCanny, Anthony ; McManus, Emma ; McWay, Ryan ; Metson, Lennard ; Kinge, Jonas Minet ; Mishra, Sumit ; Mohnen, Myra ; Möller, Jakob ; Montambeault, Rosalie ; Montpetit, Sébastien ; Morin, Louis-Philippe ; Morris, Todd ; Moser, Scott ; Motoki, Fabio ; Muehlenbachs, Lucija ; Musulan, Andreea ; Musumeci, Marco ; Nabin, Munirul ; Nchare, Karim ; Neubauer, Florian ; Nguyen, Quan M. P. ; Nguyen, Tuan ; Nguyen-Tien, Viet ; Niazi, Ali ; Nikolaishvili, Giorgi ; Nordstrom, Ardyn ; Nü, Patrick ; Odermatt, Angela ; Olson, Matt ; ien, Henning ; Ölkers, Tim ; Vert, Miquel Oliver i. ; Oral, Emre ; Oswald, Christian ; Ousman, Ali ; Özak, Ömer ; Pandey, Shubham ; Pavlov, Alexandre ; Pelli, Martino ; Penheiro, Romeo ; Park, RyuGyung ; Martel, Eva Pérez ; Petrovičová, Tereza ; Phan, Linh ; Prettyman, Alexa ; Procházka, Jakub ; Putri, Aqila ; Quandt, Julian ; Qiu, Kangyu ; Nguyen, Loan Quynh Thi ; Rahman, Andaleeb ; Rea, Carson H. ; Reiremo, Adam ; Renée, Laëtitia ; Richardson, Joseph ; Rivers, Nicholas ; Rodrigues, Bruno ; Roelofs, William ; Roemer, Tobias ; Rogeberg, Ole ; Rose, Julian ; Roskos-Ewoldsen, Andrew ; Rosmer, Paul ; Sabada, Barbara ; Saberian, Soodeh ; Salamanca, Nicolas ; Sator, Georg ; Sawyer, Antoine ; Scates, Daniel ; Schlüter, Elmar ; Sells, Cameron ; Sen, Sharmi ; Sethi, Ritika ; Shcherbiak, Anna ; Sogaolu, Moyosore ; Soosalu, Matt ; Srensen, Erik ; Sovani, Manali ; Spencer, Noah ; Staubli, Stefan ; Stans, Renske ; Stewart, Anya ; Stips, Felix ; Stockley, Kieran ; Strobel, Stephenson ; Struby, Ethan ; Tang, John ; Tanrisever, Idil ; Yang, Thomas Tao ; Tastan, Ipek ; Tatić, Dejan ; Tatlow, Benjamin ; Seuyong, Féraud Tchuisseu ; Thériault, Rémi ; Thivierge, Vincent ; Tian, Wenjie ; Toma, Filip-Mihai ; Totarelli, Maddalena ; Tran, Van-Anh ; Truong, Hung ; Tsoy, Nikita ; Tuzcuoglu, Kerem ; Ubfal, Diego ; Villalobos, Laura ; Walterskirchen, Julian ; Wang, Joseph Taoyi ; Wattal, Vasudha ; Webb, Matthew D. ; Weber, Bryan ; Weisser, Reinhard ; Weng, Wei-Chien ; Westheide, Christian ; White, Kimberly ; Winter, Jacob ; Wochner, Timo ; Woerman, Matt ; Wong, Jared ; Woodard, Ritchie ; Wroński, Marcin ; Yazbeck, Myra ; Yang, Gustav Chung ; Yap, Luther ; Yassin, Kareman ; Ye, Hao ; Yoon, Jin Young ; Yurris, Chris ; Zahra, Tahreen ; Zaneva, Mirela ; Zayat, Aline ; Zhang, Jonathan ; Zhao, Ziwei ; Yaolang, Zhong
This study pushes our understanding of research reliability by reproducing and replicating claims from 110 papers in leading economic and political science journals. The analysis involves computational reproducibility checks and robustness assessments. It reveals several patterns. First, we uncover a high rate of fully computationally reproducible results (over 85%). Second, excluding minor issues like missing packages or broken pathways, we uncover coding errors for about 25% of studies, with some studies containing multiple errors. Third, we test the robustness of the results to 5,511 re-analyses. We find a robustness reproducibility of about 70%. Robustness reproducibility rates are relatively higher for re-analyses that introduce new data and lower for re-analyses that change the sample or the definition of the dependent variable. Fourth, 52% of re-analysis effect size estimates are smaller than the original published estimates and the average statistical significance of a re-analysis is 77% of the original. Lastly, we rely on six teams of researchers working independently to answer eight additional research questions on the determinants of robustness reproducibility. Most teams find a negative relationship between replicators' experience and reproducibility, while finding no relationship between reproducibility and the provision of intermediate or even raw data combined with the necessary cleaning codes.
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