@article{WuttkeLiLietal.2019, author = {Wuttke, Matthias and Li, Yong and Li, Man and Sieber, Karsten B. and Feitosa, Mary F. and Gorski, Mathias and Tin, Adrienne and Wang, Lihua and Chu, Audrey Y. and Hoppmann, Anselm and Kirsten, Holger and Giri, Ayush and Chai, Jin-Fang and Sveinbjornsson, Gardar and Tayo, Bamidele O. and Nutile, Teresa and Fuchsberger, Christian and Marten, Jonathan and Cocca, Massimiliano and Ghasemi, Sahar and Xu, Yizhe and Horn, Katrin and Noce, Damia and Van der Most, Peter J. and Sedaghat, Sanaz and Yu, Zhi and Akiyama, Masato and Afaq, Saima and Ahluwalia, Tarunveer Singh and Almgren, Peter and Amin, Najaf and Arnlov, Johan and Bakker, Stephan J. L. and Bansal, Nisha and Baptista, Daniela and Bergmann, Sven and Biggs, Mary L. and Biino, Ginevra and Boehnke, Michael and Boerwinkle, Eric and Boissel, Mathilde and B{\"o}ttinger, Erwin and Boutin, Thibaud S. and Brenner, Hermann and Brumat, Marco and Burkhardt, Ralph and Butterworth, Adam S. and Campana, Eric and Campbell, Archie and Campbell, Harry and Canouil, Mickael and Carroll, Robert J. and Catamo, Eulalia and Chambers, John C. and Chee, Miao-Ling and Chee, Miao-Li and Chen, Xu and Cheng, Ching-Yu and Cheng, Yurong and Christensen, Kaare and Cifkova, Renata and Ciullo, Marina and Concas, Maria Pina and Cook, James P. and Coresh, Josef and Corre, Tanguy and Sala, Cinzia Felicita and Cusi, Daniele and Danesh, John and Daw, E. Warwick and De Borst, Martin H. and De Grandi, Alessandro and De Mutsert, Renee and De Vries, Aiko P. J. and Degenhardt, Frauke and Delgado, Graciela and Demirkan, Ayse and Di Angelantonio, Emanuele and Dittrich, Katalin and Divers, Jasmin and Dorajoo, Rajkumar and Eckardt, Kai-Uwe and Ehret, Georg and Elliott, Paul and Endlich, Karlhans and Evans, Michele K. and Felix, Janine F. and Foo, Valencia Hui Xian and Franco, Oscar H. and Franke, Andre and Freedman, Barry I. and Freitag-Wolf, Sandra and Friedlander, Yechiel and Froguel, Philippe and Gansevoort, Ron T. and Gao, He and Gasparini, Paolo and Gaziano, J. Michael and Giedraitis, Vilmantas and Gieger, Christian and Girotto, Giorgia and Giulianini, Franco and Gogele, Martin and Gordon, Scott D. and Gudbjartsson, Daniel F. and Gudnason, Vilmundur and Haller, Toomas and Hamet, Pavel and Harris, Tamara B. and Hartman, Catharina A. and Hayward, Caroline and Hellwege, Jacklyn N. and Heng, Chew-Kiat and Hicks, Andrew A. and Hofer, Edith and Huang, Wei and Hutri-Kahonen, Nina and Hwang, Shih-Jen and Ikram, M. Arfan and Indridason, Olafur S. and Ingelsson, Erik and Ising, Marcus and Jaddoe, Vincent W. V. and Jakobsdottir, Johanna and Jonas, Jost B. and Joshi, Peter K. and Josyula, Navya Shilpa and Jung, Bettina and Kahonen, Mika and Kamatani, Yoichiro and Kammerer, Candace M. and Kanai, Masahiro and Kastarinen, Mika and Kerr, Shona M. and Khor, Chiea-Chuen and Kiess, Wieland and Kleber, Marcus E. and Koenig, Wolfgang and Kooner, Jaspal S. and Korner, Antje and Kovacs, Peter and Kraja, Aldi T. and Krajcoviechova, Alena and Kramer, Holly and Kramer, Bernhard K. and Kronenberg, Florian and Kubo, Michiaki and Kuhnel, Brigitte and Kuokkanen, Mikko and Kuusisto, Johanna and La Bianca, Martina and Laakso, Markku and Lange, Leslie A. and Langefeld, Carl D. and Lee, Jeannette Jen-Mai and Lehne, Benjamin and Lehtimaki, Terho and Lieb, Wolfgang and Lim, Su-Chi and Lind, Lars and Lindgren, Cecilia M. and Liu, Jun and Liu, Jianjun and Loeffler, Markus and Loos, Ruth J. F. and Lucae, Susanne and Lukas, Mary Ann and Lyytikainen, Leo-Pekka and Magi, Reedik and Magnusson, Patrik K. E. and Mahajan, Anubha and Martin, Nicholas G. and Martins, Jade and Marz, Winfried and Mascalzoni, Deborah and Matsuda, Koichi and Meisinger, Christa and Meitinger, Thomas and Melander, Olle and Metspalu, Andres and Mikaelsdottir, Evgenia K. and Milaneschi, Yuri and Miliku, Kozeta and Mishra, Pashupati P. and Program, V. A. Million Veteran and Mohlke, Karen L. and Mononen, Nina and Montgomery, Grant W. and Mook-Kanamori, Dennis O. and Mychaleckyj, Josyf C. and Nadkarni, Girish N. and Nalls, Mike A. and Nauck, Matthias and Nikus, Kjell and Ning, Boting and Nolte, Ilja M. and Noordam, Raymond and Olafsson, Isleifur and Oldehinkel, Albertine J. and Orho-Melander, Marju and Ouwehand, Willem H. and Padmanabhan, Sandosh and Palmer, Nicholette D. and Palsson, Runolfur and Penninx, Brenda W. J. H. and Perls, Thomas and Perola, Markus and Pirastu, Mario and Pirastu, Nicola and Pistis, Giorgio and Podgornaia, Anna I. and Polasek, Ozren and Ponte, Belen and Porteous, David J. and Poulain, Tanja and Pramstaller, Peter P. and Preuss, Michael H. and Prins, Bram P. and Province, Michael A. and Rabelink, Ton J. and Raffield, Laura M. and Raitakari, Olli T. and Reilly, Dermot F. and Rettig, Rainer and Rheinberger, Myriam and Rice, Kenneth M. and Ridker, Paul M. and Rivadeneira, Fernando and Rizzi, Federica and Roberts, David J. and Robino, Antonietta and Rossing, Peter and Rudan, Igor and Rueedi, Rico and Ruggiero, Daniela and Ryan, Kathleen A. and Saba, Yasaman and Sabanayagam, Charumathi and Salomaa, Veikko and Salvi, Erika and Saum, Kai-Uwe and Schmidt, Helena and Schmidt, Reinhold and Ben Schottker, and Schulz, Christina-Alexandra and Schupf, Nicole and Shaffer, Christian M. and Shi, Yuan and Smith, Albert V. and Smith, Blair H. and Soranzo, Nicole and Spracklen, Cassandra N. and Strauch, Konstantin and Stringham, Heather M. and Stumvoll, Michael and Svensson, Per O. and Szymczak, Silke and Tai, E-Shyong and Tajuddin, Salman M. and Tan, Nicholas Y. Q. and Taylor, Kent D. and Teren, Andrej and Tham, Yih-Chung and Thiery, Joachim and Thio, Chris H. L. and Thomsen, Hauke and Thorleifsson, Gudmar and Toniolo, Daniela and Tonjes, Anke and Tremblay, Johanne and Tzoulaki, Ioanna and Uitterlinden, Andre G. and Vaccargiu, Simona and Van Dam, Rob M. and Van der Harst, Pim and Van Duijn, Cornelia M. and Edward, Digna R. Velez and Verweij, Niek and Vogelezang, Suzanne and Volker, Uwe and Vollenweider, Peter and Waeber, Gerard and Waldenberger, Melanie and Wallentin, Lars and Wang, Ya Xing and Wang, Chaolong and Waterworth, Dawn M. and Bin Wei, Wen and White, Harvey and Whitfield, John B. and Wild, Sarah H. and Wilson, James F. and Wojczynski, Mary K. and Wong, Charlene and Wong, Tien-Yin and Xu, Liang and Yang, Qiong and Yasuda, Masayuki and Yerges-Armstrong, Laura M. and Zhang, Weihua and Zonderman, Alan B. and Rotter, Jerome I. and Bochud, Murielle and Psaty, Bruce M. and Vitart, Veronique and Wilson, James G. and Dehghan, Abbas and Parsa, Afshin and Chasman, Daniel I. and Ho, Kevin and Morris, Andrew P. and Devuyst, Olivier and Akilesh, Shreeram and Pendergrass, Sarah A. and Sim, Xueling and Boger, Carsten A. and Okada, Yukinori and Edwards, Todd L. and Snieder, Harold and Stefansson, Kari and Hung, Adriana M. and Heid, Iris M. and Scholz, Markus and Teumer, Alexander and Kottgen, Anna and Pattaro, Cristian}, title = {A catalog of genetic loci associated with kidney function from analyses of a million individuals}, series = {Nature genetics}, volume = {51}, journal = {Nature genetics}, number = {6}, publisher = {Nature Publ. Group}, address = {New York}, organization = {Lifelines COHort Study}, issn = {1061-4036}, doi = {10.1038/s41588-019-0407-x}, pages = {957 -- +}, year = {2019}, abstract = {Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.}, language = {en} } @article{TangSullivanHongetal.2019, author = {Tang, Alan T. and Sullivan, Katie Rose and Hong, Courtney C. and Goddard, Lauren M. and Mahadevan, Aparna and Ren, Aileen and Pardo, Heidy and Peiper, Amy and Griffin, Erin and Tanes, Ceylan and Mattei, Lisa M. and Yang, Jisheng and Li, Li and Mericko-Ishizuka, Patricia and Shen, Le and Hobson, Nicholas and Girard, Romuald and Lightle, Rhonda and Moore, Thomas and Shenkar, Robert and Polster, Sean P. and Roedel, Claudia Jasmin and Li, Ning and Zhu, Qin and Whitehead, Kevin J. and Zheng, Xiangjian and Akers, Amy and Morrison, Leslie and Kim, Helen and Bittinger, Kyle and Lengner, Christopher J. and Schwaninger, Markus and Velcich, Anna and Augenlicht, Leonard and Abdelilah-Seyfried, Salim and Min, Wang and Marchuk, Douglas A. and Awad, Issam A. and Kahn, Mark L.}, title = {Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation}, series = {Science Translational Medicine}, volume = {11}, journal = {Science Translational Medicine}, number = {520}, publisher = {American Assoc. for the Advancement of Science}, address = {Washington}, issn = {1946-6234}, doi = {10.1126/scitranslmed.aaw3521}, pages = {14}, year = {2019}, abstract = {Cerebral cavernous malformation (CCM) is a genetic, cerebrovascular disease. Familial CCM is caused by genetic mutations in KRIT1, CCM2, or PDCD10. Disease onset is earlier and more severe in individuals with PDCD10 mutations. Recent studies have shown that lesions arise from excess mitogen-activated protein kinase kinase kinase 3 (MEKK3) signaling downstream of Toll-like receptor 4 (TLR4) stimulation by lipopolysaccharide derived from the gut microbiome. These findings suggest a gut-brain CCM disease axis but fail to define it or explain the poor prognosis of patients with PDCD10 mutations. Here, we demonstrate that the gut barrier is a primary determinant of CCM disease course, independent of microbiome configuration, that explains the increased severity of CCM disease associated with PDCD10 deficiency. Chemical disruption of the gut barrier with dextran sulfate sodium augments CCM formation in a mouse model, as does genetic loss of Pdcd10, but not Krit1, in gut epithelial cells. Loss of gut epithelial Pdcd10 results in disruption of the colonic mucosal barrier. Accordingly, loss of Mucin-2 or exposure to dietary emulsifiers that reduce the mucus barrier increases CCM burden analogous to loss of Pdcd10 in the gut epithelium. Last, we show that treatment with dexamethasone potently inhibits CCM formation in mice because of the combined effect of action at both brain endothelial cells and gut epithelial cells. These studies define a gut-brain disease axis in an experimental model of CCM in which a single gene is required for two critical components: gut epithelial function and brain endothelial signaling.}, language = {en} } @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{MiddeldorpMahajanHorikoshietal.2019, author = {Middeldorp, Christel M. and Mahajan, Anubha and Horikoshi, Momoko and Robertson, Neil R. and Beaumont, Robin N. and Bradfield, Jonathan P. and Bustamante, Mariona and Cousminer, Diana L. and Day, Felix R. and De Silva, N. Maneka and Guxens, Monica and Mook-Kanamori, Dennis O. and St Pourcain, Beate and Warrington, Nicole M. and Adair, Linda S. and Ahlqvist, Emma and Ahluwalia, Tarunveer Singh and Almgren, Peter and Ang, Wei and Atalay, Mustafa and Auvinen, Juha and Bartels, Meike and Beckmann, Jacques S. and Bilbao, Jose Ramon and Bond, Tom and Borja, Judith B. and Cavadino, Alana and Charoen, Pimphen and Chen, Zhanghua and Coin, Lachlan and Cooper, Cyrus and Curtin, John A. and Custovic, Adnan and Das, Shikta and Davies, Gareth E. and Dedoussis, George V. and Duijts, Liesbeth and Eastwood, Peter R. and Eliasen, Anders U. and Elliott, Paul and Eriksson, Johan G. and Estivill, Xavier and Fadista, Joao and Fedko, Iryna O. and Frayling, Timothy M. and Gaillard, Romy and Gauderman, W. James and Geller, Frank and Gilliland, Frank and Gilsanz, Vincente and Granell, Raquel and Grarup, Niels and Groop, Leif and Hadley, Dexter and Hakonarson, Hakon and Hansen, Torben and Hartman, Catharina A. and Hattersley, Andrew T. and Hayes, M. Geoffrey and Hebebrand, Johannes and Heinrich, Joachim and Helgeland, Oyvind and Henders, Anjali K. and Henderson, John and Henriksen, Tine B. and Hirschhorn, Joel N. and Hivert, Marie-France and Hocher, Berthold and Holloway, John W. and Holt, Patrick and Hottenga, Jouke-Jan and Hypponen, Elina and Iniguez, Carmen and Johansson, Stefan and Jugessur, Astanand and Kahonen, Mika and Kalkwarf, Heidi J. and Kaprio, Jaakko and Karhunen, Ville and Kemp, John P. and Kerkhof, Marjan and Koppelman, Gerard H. and Korner, Antje and Kotecha, Sailesh and Kreiner-Moller, Eskil and Kulohoma, Benard and Kumar, Ashish and Kutalik, Zoltan and Lahti, Jari and Lappe, Joan M. and Larsson, Henrik and Lehtimaki, Terho and Lewin, Alexandra M. and Li, Jin and Lichtenstein, Paul and Lindgren, Cecilia M. and Lindi, Virpi and Linneberg, Allan and Liu, Xueping and Liu, Jun and Lowe, William L. and Lundstrom, Sebastian and Lyytikainen, Leo-Pekka and Ma, Ronald C. W. and Mace, Aurelien and Magi, Reedik and Magnus, Per and Mamun, Abdullah A. and Mannikko, Minna and Martin, Nicholas G. and Mbarek, Hamdi and McCarthy, Nina S. and Medland, Sarah E. and Melbye, Mads and Melen, Erik and Mohlke, Karen L. and Monnereau, Claire and Morgen, Camilla S. and Morris, Andrew P. and Murray, Jeffrey C. and Myhre, Ronny and Najman, Jackob M. and Nivard, Michel G. and Nohr, Ellen A. and Nolte, Ilja M. and Ntalla, Ioanna and Oberfield, Sharon E. and Oken, Emily and Oldehinkel, Albertine J. and Pahkala, Katja and Palviainen, Teemu and Panoutsopoulou, Kalliope and Pedersen, Oluf and Pennell, Craig E. and Pershagen, Goran and Pitkanen, Niina and Plomin, Robert and Power, Christine and Prasad, Rashmi B. and Prokopenko, Inga and Pulkkinen, Lea and Raikkonen, Katri and Raitakari, Olli T. and Reynolds, Rebecca M. and Richmond, Rebecca C. and Rivadeneira, Fernando and Rodriguez, Alina and Rose, Richard J. and Salem, Rany and Santa-Marina, Loreto and Saw, Seang-Mei and Schnurr, Theresia M. and Scott, James G. and Selzam, Saskia and Shepherd, John A. and Simpson, Angela and Skotte, Line and Sleiman, Patrick M. A. and Snieder, Harold and Sorensen, Thorkild I. A. and Standl, Marie and Steegers, Eric A. P. and Strachan, David P. and Straker, Leon and Strandberg, Timo and Taylor, Michelle and Teo, Yik-Ying and Thiering, Elisabeth and Torrent, Maties and Tyrrell, Jessica and Uitterlinden, Andre G. and van Beijsterveldt, Toos and van der Most, Peter J. and van Duijn, Cornelia M. and Viikari, Jorma and Vilor-Tejedor, Natalia and Vogelezang, Suzanne and Vonk, Judith M. and Vrijkotte, Tanja G. M. and Vuoksimaa, Eero and Wang, Carol A. and Watkins, William J. and Wichmann, H-Erich and Willemsen, Gonneke and Williams, Gail M. and Wilson, James F. and Wray, Naomi R. and Xu, Shujing and Xu, Cheng-Jian and Yaghootkar, Hanieh and Yi, Lu and Zafarmand, Mohammad Hadi and Zeggini, Eleftheria and Zemel, Babette S. and Hinney, Anke and Lakka, Timo A. and Whitehouse, Andrew J. O. and Sunyer, Jordi and Widen, Elisabeth E. and Feenstra, Bjarke and Sebert, Sylvain and Jacobsson, Bo and Njolstad, Pal R. and Stoltenberg, Camilla and Smith, George Davey and Lawlor, Debbie A. and Paternoster, Lavinia and Timpson, Nicholas J. and Ong, Ken K. and Bisgaard, Hans and Bonnelykke, Klaus and Jaddoe, Vincent W. V. and Tiemeier, Henning and Jarvelin, Marjo-Riitta and Evans, David M. and Perry, John R. B. and Grant, Struan F. A. and Boomsma, Dorret I. and Freathy, Rachel M. and McCarthy, Mark I. and Felix, Janine F.}, title = {The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia}, series = {European journal of epidemiology}, volume = {34}, journal = {European journal of epidemiology}, number = {3}, publisher = {Springer}, address = {Dordrecht}, organization = {EArly Genetics Lifecourse EGG Consortium EGG Membership EAGLE Membership}, issn = {0393-2990}, doi = {10.1007/s10654-019-00502-9}, pages = {279 -- 300}, year = {2019}, abstract = {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.}, language = {en} } @article{WilkinParrishYangetal.2019, author = {Wilkin, Kyle J. and Parrish, Robert M. and Yang, Jie and Wolf, Thomas J. A. and Nunes, J. Pedro F. and G{\"u}hr, Markus and Li, Renkai and Shen, Xiaozhe and Zheng, Qiang and Wang, Xijie and Martinez, Todd J. and Centurion, Martin}, title = {Diffractive imaging of dissociation and ground-state dynamics in a complex molecule}, series = {Physical review : A, Atomic, molecular, and optical physics}, volume = {100}, journal = {Physical review : A, Atomic, molecular, and optical physics}, number = {2}, publisher = {American Physical Society}, address = {College Park}, issn = {2469-9926}, doi = {10.1103/PhysRevA.100.023402}, pages = {10}, year = {2019}, abstract = {We have investigated the structural dynamics in photoexcited 1,2-diiodotetrafluoroethane molecules (C2F4I2) in the gas phase experimentally using ultrafast electron diffraction and theoretically using FOMO-CASCI excited-state dynamics simulations. The molecules are excited by an ultraviolet femtosecond laser pulse to a state characterized by a transition from the iodine 5p perpendicular to orbital to a mixed 5p parallel to sigma hole and CF2 center dot antibonding orbital, which results in the cleavage of one of the carbon-iodine bonds. We have observed, with sub-Angstrom resolution, the motion of the nuclear wave packet of the dissociating iodine atom followed by coherent vibrations in the electronic ground state of the C2F4I radical. The radical reaches a stable classical (nonbridged) structure in less than 200 fs.}, language = {en} } @article{WolfSanchezYangetal.2019, author = {Wolf, Thomas J. A. and Sanchez, David M. and Yang, J. and Parrish, R. M. and Nunes, J. P. F. and Centurion, M. and Coffee, R. and Cryan, J. P. and G{\"u}hr, Markus and Hegazy, Kareem and Kirrander, Adam and Li, R. K. and Ruddock, J. and Shen, Xiaozhe and Vecchione, T. and Weathersby, S. P. and Weber, Peter M. and Wilkin, K. and Yong, Haiwang and Zheng, Q. and Wang, X. J. and Minitti, Michael P. and Martinez, Todd J.}, title = {The photochemical ring-opening of 1,3-cyclohexadiene imaged by ultrafast electron diffraction}, series = {Nature chemistry}, volume = {11}, journal = {Nature chemistry}, number = {6}, publisher = {Nature Publ. Group}, address = {London}, issn = {1755-4330}, doi = {10.1038/s41557-019-0252-7}, pages = {504 -- 509}, year = {2019}, abstract = {The ultrafast photoinduced ring-opening of 1,3-cyclohexadiene constitutes a textbook example of electrocyclic reactions in organic chemistry and a model for photobiological reactions in vitamin D synthesis. Although the relaxation from the photoexcited electronic state during the ring-opening has been investigated in numerous studies, the accompanying changes in atomic distance have not been resolved. Here we present a direct and unambiguous observation of the ring-opening reaction path on the femtosecond timescale and subangstrom length scale using megaelectronvolt ultrafast electron diffraction. We followed the carbon-carbon bond dissociation and the structural opening of the 1,3-cyclohexadiene ring by the direct measurement of time-dependent changes in the distribution of interatomic distances. We observed a substantial acceleration of the ring-opening motion after internal conversion to the ground state due to a steepening of the electronic potential gradient towards the product minima. The ring-opening motion transforms into rotation of the terminal ethylene groups in the photoproduct 1,3,5-hexatriene on the subpicosecond timescale.}, language = {en} } @article{WangFosterYanetal.2019, author = {Wang, Xiaoxi and Foster, William J. and Yan, J. and Li, A. and Mutti, Maria}, title = {Delayed recovery of metazoan reefs on the Laibin-Heshan platform margin following the Middle Permian (Capitanian) mass extinction}, series = {Global and planetary change}, volume = {180}, journal = {Global and planetary change}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0921-8181}, doi = {10.1016/j.gloplacha.2019.05.005}, pages = {1 -- 15}, year = {2019}, abstract = {Following the Middle Permian (Capitanian) mass extinction there was a global 'reef eclipse', and this event had an important role in the Paleozoic-Mesozoic transition of reef ecosystems. Furthermore, the recovery pattern of reef ecosystems in the Wuchiapingian of South China, before the radiation of Changhsingian reefs, is poorly understood. Here, we present a detailed sedimentological account of the Tieqiao section, South China, which records the only known Wuchiapingian reef setting from South China. Six reef growing phases were identified within six transgressive-regressive cycles. The cycles represent changes of deposition in a shallow basin to a subtidal outer platform setting, and the reefal build-ups are recorded in the shallowest part of the cycles above wave base in the euphotic zone. Our results show that the initial reef recovery started from the shallowing up part of the 1st cycle, within the Clarkina leveni conodont zone, which is two conodont zones earlier than previously recognized. In addition, even though metazoans, such as sponges, do become important in the development of the reef bodies, they are not a major component until later in the Wuchiapingian in the 5th and 6th transgressive-regressive cycles. This suggests a delayed recovery of metazoan reef ecosystems following the Middle Permian extinction. Furthermore, even though sponges do become abundant within the reefs, it is the presence and growth of the encrusters Archaeolithoporella and Tubiphytes and abundance of microbial micrites that play an important role in stabilizing the reef structures that form topographic highs.}, language = {en} } @article{ChapmanLantOhashietal.2019, author = {Chapman, Eric M. and Lant, Benjamin and Ohashi, Yota and Yu, Bin and Schertzberg, Michael and Go, Christopher and Dogra, Deepika and Koskimaki, Janne and Girard, Romuald and Li, Yan and Fraser, Andrew G. and Awad, Issam A. and Abdelilah-Seyfried, Salim and Gingras, Anne-Claude and Derry, William Brent}, title = {A conserved CCM complex promotes apoptosis non-autonomously by regulating zinc homeostasis}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, publisher = {Nature Publ. Group}, address = {London}, issn = {2041-1723}, doi = {10.1038/s41467-019-09829-z}, pages = {15}, year = {2019}, abstract = {Apoptotic death of cells damaged by genotoxic stress requires regulatory input from surrounding tissues. The C. elegans scaffold protein KRI-1, ortholog of mammalian KRIT1/CCM1, permits DNA damage-induced apoptosis of cells in the germline by an unknown cell non-autonomous mechanism. We reveal that KRI-1 exists in a complex with CCM-2 in the intestine to negatively regulate the ERK-5/MAPK pathway. This allows the KLF-3 transcription factor to facilitate expression of the SLC39 zinc transporter gene zipt-2.3, which functions to sequester zinc in the intestine. Ablation of KRI-1 results in reduced zinc sequestration in the intestine, inhibition of IR-induced MPK-1/ERK1 activation, and apoptosis in the germline. Zinc localization is also perturbed in the vasculature of krit1(-/-) zebrafish, and SLC39 zinc transporters are mis-expressed in Cerebral Cavernous Malformations (CCM) patient tissues. This study provides new insights into the regulation of apoptosis by cross-tissue communication, and suggests a link between zinc localization and CCM disease.}, language = {en} } @article{CookLiCaietal.2019, author = {Cook, Katherine V. and Li, Chuang and Cai, Haiyuan and Krumholz, Lee R. and Hambright, K. David and Paerl, Hans W. and Steffen, Morgan M. and Wilson, Alan E. and Burford, Michele A. and Grossart, Hans-Peter and Hamilton, David P. and Jiang, Helong and Sukenik, Assaf and Latour, Delphine and Meyer, Elisabeth I. and Padisak, Judit and Qin, Boqiang and Zamor, Richard M. and Zhu, Guangwei}, title = {The global Microcystis interactome}, series = {Limnology and oceanography}, volume = {65}, journal = {Limnology and oceanography}, publisher = {Wiley}, address = {Hoboken}, issn = {0024-3590}, doi = {10.1002/lno.11361}, pages = {S194 -- S207}, year = {2019}, abstract = {Bacteria play key roles in the function and diversity of aquatic systems, but aside from study of specific bloom systems, little is known about the diversity or biogeography of bacteria associated with harmful cyanobacterial blooms (cyanoHABs). CyanoHAB species are known to shape bacterial community composition and to rely on functions provided by the associated bacteria, leading to the hypothesized cyanoHAB interactome, a coevolved community of synergistic and interacting bacteria species, each necessary for the success of the others. Here, we surveyed the microbiome associated with Microcystis aeruginosa during blooms in 12 lakes spanning four continents as an initial test of the hypothesized Microcystis interactome. We predicted that microbiome composition and functional potential would be similar across blooms globally. Our results, as revealed by 16S rRNA sequence similarity, indicate that M. aeruginosa is cosmopolitan in lakes across a 280 degrees longitudinal and 90 degrees latitudinal gradient. The microbiome communities were represented by a wide range of operational taxonomic units and relative abundances. Highly abundant taxa were more related and shared across most sites and did not vary with geographic distance, thus, like Microcystis, revealing no evidence for dispersal limitation. High phylogenetic relatedness, both within and across lakes, indicates that microbiome bacteria with similar functional potential were associated with all blooms. While Microcystis and the microbiome bacteria shared many genes, whole-community metagenomic analysis revealed a suite of biochemical pathways that could be considered complementary. Our results demonstrate a high degree of similarity across global Microcystis blooms, thereby providing initial support for the hypothesized Microcystis interactome.}, language = {en} } @article{ComasBruHarrisonWerneretal.2019, author = {Comas-Bru, Laia and Harrison, Sandy P. and Werner, Martin and Rehfeld, Kira and Scroxton, Nick and Veiga-Pires, Cristina and Ahmad, Syed Masood and Brahim, Yassine Ait and Mozhdehi, Sahar Amirnezhad and Arienzo, Monica and Atsawawaranunt, Kamolphat and Baker, Andy and Braun, Kerstin and Breitenbach, Sebastian Franz Martin and Burstyn, Yuval and Chawchai, Sakonvan and Columbu, Andrea and Deininger, Michael and Demeny, Attila and Dixon, Bronwyn and Hatvani, Istvan Gabor and Hu, Jun and Kaushal, Nikita and Kern, Zoltan and Labuhn, Inga and Lachniet, Matthew S. and Lechleitner, Franziska A. and Lorrey, Andrew and Markowska, Monika and Nehme, Carole and Novello, Valdir F. and Oster, Jessica and Perez-Mejias, Carlos and Pickering, Robyn and Sekhon, Natasha and Wang, Xianfeng and Warken, Sophie and Atkinson, Tim and Ayalon, Avner and Baldini, James and Bar-Matthews, Miryam and Bernal, Juan Pablo and Boch, Ronny and Borsato, Andrea and Boyd, Meighan and Brierley, Chris and Cai, Yanjun and Carolin, Stacy and Cheng, Hai and Constantin, Silviu and Couchoud, Isabelle and Cruz, Francisco and Denniston, Rhawn and Dragusin, Virgil and Duan, Wuhui and Ersek, Vasile and Finne, Martin and Fleitmann, Dominik and Fohlmeister, Jens Bernd and Frappier, Amy and Genty, Dominique and Holzkamper, Steffen and Hopley, Philip and Johnston, Vanessa and Kathayat, Gayatri and Keenan-Jones, Duncan and Koltai, Gabriella and Li, Ting-Yong and Lone, Mahjoor Ahmad and Luetscher, Marc and Mattey, Dave and Moreno, Ana and Moseley, Gina and Psomiadis, David and Ruan, Jiaoyang and Scholz, Denis and Sha, Lijuan and Smith, Andrew Christopher and Strikis, Nicolas and Treble, Pauline and Unal-Imer, Ezgi and Vaks, Anton and Vansteenberge, Stef and Voarintsoa, Ny Riavo G. and Wong, Corinne and Wortham, Barbara and Wurtzel, Jennifer and Zhang, Haiwei}, title = {Evaluating model outputs using integrated global speleothem records of climate change since the last glacial}, series = {Climate of the past : an interactive open access journal of the European Geosciences Union}, volume = {15}, journal = {Climate of the past : an interactive open access journal of the European Geosciences Union}, number = {4}, publisher = {Copernicus}, address = {G{\"o}ttingen}, organization = {SISAL Working Grp}, issn = {1814-9324}, doi = {10.5194/cp-15-1557-2019}, pages = {1557 -- 1579}, year = {2019}, abstract = {Although quantitative isotope data from speleothems has been used to evaluate isotope-enabled model simulations, currently no consensus exists regarding the most appropriate methodology through which to achieve this. A number of modelling groups will be running isotope-enabled palaeoclimate simulations in the framework of the Coupled Model Intercomparison Project Phase 6, so it is timely to evaluate different approaches to using the speleothem data for data-model comparisons. Here, we illustrate this using 456 globally distributed speleothem δ18O records from an updated version of the Speleothem Isotopes Synthesis and Analysis (SISAL) database and palaeoclimate simulations generated using the ECHAM5-wiso isotope-enabled atmospheric circulation model. We show that the SISAL records reproduce the first-order spatial patterns of isotopic variability in the modern day, strongly supporting the application of this dataset for evaluating model-derived isotope variability into the past. However, the discontinuous nature of many speleothem records complicates the process of procuring large numbers of records if data-model comparisons are made using the traditional approach of comparing anomalies between a control period and a given palaeoclimate experiment. To circumvent this issue, we illustrate techniques through which the absolute isotope values during any time period could be used for model evaluation. Specifically, we show that speleothem isotope records allow an assessment of a model's ability to simulate spatial isotopic trends. Our analyses provide a protocol for using speleothem isotope data for model evaluation, including screening the observations to take into account the impact of speleothem mineralogy on δ18O values, the optimum period for the modern observational baseline and the selection of an appropriate time window for creating means of the isotope data for palaeo-time-slices.}, language = {en} }