Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels
Tin, Adrienne; Marten, Jonathan; Halperin Kuhns, Victoria L; Li, Yong; Wuttke, Matthias; Kirsten, Holger; Sieber, Karsten B; Qiu, Chengxiang; Gorski, Mathias; Yu, Zhi; Giri, Ayush; Sveinbjornsson, Gardar; Li, Man; Chu, Audrey Y; Hoppmann, Anselm; O'Connor, Luke J; Prins, Bram; Nutile, Teresa; Noce, Damia; Akiyama, Masato; Cocca, Massimiliano; Ghasemi, Sahar; van der Most, Peter J; Horn, Katrin; Xu, Yizhe; Fuchsberger, Christian; Sedaghat, Sanaz; Afaq, Saima; Amin, Najaf; Ärnlöv, Johan; Bakker, Stephan J L; Bansal, Nisha; Baptista, Daniela; Bergmann, Sven; Biggs, Mary L; Biino, Ginevra; Boerwinkle, Eric; Bottinger, Erwin P; Boutin, Thibaud S; Brumat, Marco; Burkhardt, Ralph; Campana, Eric; Campbell, Archie; Campbell, Harry; Carroll, Robert J; Catamo, Eulalia; Chambers, John C; Ciullo, Marina; Concas, Maria Pina; Coresh, Josef; Corre, Tanguy; Cusi, Daniele; Felicita, Sala Cinzia; de Borst, Martin H; De Grandi, Alessandro; de Mutsert, Renée; de Vries, Aiko P J; Delgado, Graciela; Demirkan, Ayşe; Devuyst, Olivier; Dittrich, Katalin; Eckardt, Kai-Uwe; Ehret, Georg; Endlich, Karlhans; Evans, Michele K; Gansevoort, Ron T; Gasparini, Paolo; Giedraitis, Vilmantas; Gieger, Christian; Girotto, Giorgia; Gögele, Martin; Gordon, Scott D; Gudbjartsson, Daniel F; Gudnason, Vilmundur; ,; Haller, Toomas; Hamet, Pavel; Harris, Tamara B; Hayward, Caroline; Hicks, Andrew A; Hofer, Edith; Holm, Hilma; Huang, Wei; Hutri-Kähönen, Nina; Hwang, Shih-Jen; Ikram, M Arfan; Lewis, Raychel M; Ingelsson, Erik; Jakobsdottir, Johanna; Jonsdottir, Ingileif; Jonsson, Helgi; Joshi, Peter K; Josyula, Navya Shilpa; Jung, Bettina; Kähönen, Mika; Kamatani, Yoichiro; Kanai, Masahiro; Kerr, Shona M; Kiess, Wieland; Kleber, Marcus E; Koenig, Wolfgang; Kooner, Jaspal S; Körner, Antje; Kovacs, Peter; Krämer, Bernhard K; Kronenberg, Florian; Kubo, Michiaki; Kühnel, Brigitte; La Bianca, Martina; Lange, Leslie A; Lehne, Benjamin; Lehtimäki, Terho; ,; Liu, Jun; Loeffler, Markus; Loos, Ruth J F; Lyytikäinen, Leo-Pekka; Magi, Reedik; Mahajan, Anubha; Martin, Nicholas G; März, Winfried; Mascalzoni, Deborah; Matsuda, Koichi; Meisinger, Christa; Meitinger, Thomas; Metspalu, Andres; Milaneschi, Yuri; ,; O'Donnell, Christopher J; Wilson, Otis D; Gaziano, J Michael; Mishra, Pashupati P; Mohlke, Karen L; Mononen, Nina; Montgomery, Grant W; Mook-Kanamori, Dennis O; Müller-Nurasyid, Martina; Nadkarni, Girish N; Nalls, Mike A; Nauck, Matthias; Nikus, Kjell; Ning, Boting; Nolte, Ilja M; Noordam, Raymond; O'Connell, Jeffrey R; Olafsson, Isleifur; Padmanabhan, Sandosh; Penninx, Brenda W J H; Perls, Thomas; Peters, Annette; Pirastu, Mario; Pirastu, Nicola; Pistis, Giorgio; Polasek, Ozren; Ponte, Belen; Porteous, David J; Poulain, Tanja; Preuss, Michael H; Rabelink, Ton J; Raffield, Laura M; Raitakari, Olli T; Rettig, Rainer; Rheinberger, Myriam; Rice, Kenneth M; Rizzi, Federica; Robino, Antonietta; Rudan, Igor; Krajcoviechova, Alena; Cifkova, Renata; Rueedi, Rico; Ruggiero, Daniela; Ryan, Kathleen A; Saba, Yasaman; Salvi, Erika; Schmidt, Helena; Schmidt, Reinhold; Shaffer, Christian M; Smith, Albert V; Smith, Blair H; Spracklen, Cassandra N; Strauch, Konstantin; Stumvoll, Michael; Sulem, Patrick; Tajuddin, Salman M; Teren, Andrej; Thiery, Joachim; Thio, Chris H L; Thorsteinsdottir, Unnur; Toniolo, Daniela; Tönjes, Anke; Tremblay, Johanne; Uitterlinden, André G; Vaccargiu, Simona; van der Harst, Pim; van Duijn, Cornelia M; Verweij, Niek; Völker, Uwe; Vollenweider, Peter; Waeber, Gerard; Waldenberger, Melanie; Whitfield, John B; Wild, Sarah H; Wilson, James F; Yang, Qiong; Zhang, Weihua; Zonderman, Alan B; Bochud, Murielle; Wilson, James G; Pendergrass, Sarah A; Ho, Kevin; Parsa, Afshin; Pramstaller, Peter P; Psaty, Bruce M; Böger, Carsten A; Snieder, Harold; Butterworth, Adam S; Okada, Yukinori; Edwards, Todd L; Stefansson, Kari; Susztak, Katalin; Scholz, Markus; Heid, Iris M; Hung, Adriana M; Teumer, Alexander; Pattaro, Cristian; Woodward, Owen M; Vitart, Veronique; Köttgen, Anna
Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.
PMCID:6858555
PMID: 31578528
ISSN: 1546-1718
CID: 5585422
Mapping 123 million neonatal, infant and child deaths between 2000 and 2017
Burstein, Roy; Henry, Nathaniel J; Collison, Michael L; Marczak, Laurie B; Sligar, Amber; Watson, Stefanie; Marquez, Neal; Abbasalizad-Farhangi, Mahdieh; Abbasi, Masoumeh; Abd-Allah, Foad; Abdoli, Amir; Abdollahi, Mohammad; Abdollahpour, Ibrahim; Abdulkader, Rizwan Suliankatchi; Abrigo, Michael R M; Acharya, Dilaram; Adebayo, Oladimeji M; Adekanmbi, Victor; Adham, Davoud; Afshari, Mahdi; Aghaali, Mohammad; Ahmadi, Keivan; Ahmadi, Mehdi; Ahmadpour, Ehsan; Ahmed, Rushdia; Akal, Chalachew Genet; Akinyemi, Joshua O; Alahdab, Fares; Alam, Noore; Alamene, Genet Melak; Alene, Kefyalew Addis; Alijanzadeh, Mehran; Alinia, Cyrus; Alipour, Vahid; Aljunid, Syed Mohamed; Almalki, Mohammed J; Al-Mekhlafi, Hesham M; Altirkawi, Khalid; Alvis-Guzman, Nelson; Amegah, Adeladza Kofi; Amini, Saeed; Amit, Arianna Maever Loreche; Anbari, Zohreh; Androudi, Sofia; Anjomshoa, Mina; Ansari, Fereshteh; Antonio, Carl Abelardo T; Arabloo, Jalal; Arefi, Zohreh; Aremu, Olatunde; Armoon, Bahram; Arora, Amit; Artaman, Al; Asadi, Anvar; Asadi-Aliabadi, Mehran; Ashraf-Ganjouei, Amir; Assadi, Reza; Ataeinia, Bahar; Atre, Sachin R; Quintanilla, Beatriz Paulina Ayala; Ayanore, Martin Amogre; Azari, Samad; Babaee, Ebrahim; Babazadeh, Arefeh; Badawi, Alaa; Bagheri, Soghra; Bagherzadeh, Mojtaba; Baheiraei, Nafiseh; Balouchi, Abbas; Barac, Aleksandra; Bassat, Quique; Baune, Bernhard T; Bayati, Mohsen; Bedi, Neeraj; Beghi, Ettore; Behzadifar, Masoud; Behzadifar, Meysam; Belay, Yared Belete; Bell, Brent; Bell, Michelle L; Berbada, Dessalegn Ajema; Bernstein, Robert S; Bhattacharjee, Natalia V; Bhattarai, Suraj; Bhutta, Zulfiqar A; Bijani, Ali; Bohlouli, Somayeh; Breitborde, Nicholas J K; Britton, Gabrielle; Browne, Annie J; Nagaraja, Sharath Burugina; Busse, Reinhard; Butt, Zahid A; Car, Josip; Cárdenas, Rosario; Castañeda-Orjuela, Carlos A; Cerin, Ester; Chanie, Wagaye Fentahun; Chatterjee, Pranab; Chu, Dinh-Toi; Cooper, Cyrus; Costa, Vera M; Dalal, Koustuv; Dandona, Lalit; Dandona, Rakhi; Daoud, Farah; Daryani, Ahmad; Das Gupta, Rajat; Davis, Ian; Davis Weaver, Nicole; Davitoiu, Dragos Virgil; De Neve, Jan-Walter; Demeke, Feleke Mekonnen; Demoz, Gebre Teklemariam; Deribe, Kebede; Desai, Rupak; Deshpande, Aniruddha; Desyibelew, Hanna Demelash; Dey, Sagnik; Dharmaratne, Samath Dhamminda; Dhimal, Meghnath; Diaz, Daniel; Doshmangir, Leila; Duraes, Andre R; Dwyer-Lindgren, Laura; Earl, Lucas; Ebrahimi, Roya; Ebrahimpour, Soheil; Effiong, Andem; Eftekhari, Aziz; Ehsani-Chimeh, Elham; El Sayed, Iman; El Sayed Zaki, Maysaa; El Tantawi, Maha; El-Khatib, Ziad; Emamian, Mohammad Hassan; Enany, Shymaa; Eskandarieh, Sharareh; Eyawo, Oghenowede; Ezalarab, Maha; Faramarzi, Mahbobeh; Fareed, Mohammad; Faridnia, Roghiyeh; Faro, Andre; Fazaeli, Ali Akbar; Fazlzadeh, Mehdi; Fentahun, Netsanet; Fereshtehnejad, Seyed-Mohammad; Fernandes, João C; Filip, Irina; Fischer, Florian; Foigt, Nataliya A; Foroutan, Masoud; Francis, Joel Msafiri; Fukumoto, Takeshi; Fullman, Nancy; Gallus, Silvano; Gebre, Destallem Gebremedhin; Gebrehiwot, Tsegaye Tewelde; Gebremeskel, Gebreamlak Gebremedhn; Gessner, Bradford D; Geta, Birhanu; Gething, Peter W; Ghadimi, Reza; Ghadiri, Keyghobad; Ghajarzadeh, Mahsa; Ghashghaee, Ahmad; Gill, Paramjit Singh; Gill, Tiffany K; Golding, Nick; Gomes, Nelson G M; Gona, Philimon N; Gopalani, Sameer Vali; Gorini, Giuseppe; Goulart, Bárbara Niegia Garcia; Graetz, Nicholas; Greaves, Felix; Green, Manfred S; Guo, Yuming; Haj-Mirzaian, Arvin; Haj-Mirzaian, Arya; Hall, Brian James; Hamidi, Samer; Haririan, Hamidreza; Haro, Josep Maria; Hasankhani, Milad; Hasanpoor, Edris; Hasanzadeh, Amir; Hassankhani, Hadi; Hassen, Hamid Yimam; Hegazy, Mohamed I; Hendrie, Delia; Heydarpour, Fatemeh; Hird, Thomas R; Hoang, Chi Linh; Hollerich, Gillian; Rad, Enayatollah Homaie; Hoseini-Ghahfarokhi, Mojtaba; Hossain, Naznin; Hosseini, Mostafa; Hosseinzadeh, Mehdi; Hostiuc, Mihaela; Hostiuc, Sorin; Househ, Mowafa; Hsairi, Mohamed; Ilesanmi, Olayinka Stephen; Imani-Nasab, Mohammad Hasan; Iqbal, Usman; Irvani, Seyed Sina Naghibi; Islam, Nazrul; Islam, Sheikh Mohammed Shariful; Jürisson, Mikk; Balalami, Nader Jafari; Jalali, Amir; Javidnia, Javad; Jayatilleke, Achala Upendra; Jenabi, Ensiyeh; Ji, John S; Jobanputra, Yash B; Johnson, Kimberly; Jonas, Jost B; Shushtari, Zahra Jorjoran; Jozwiak, Jacek Jerzy; Kabir, Ali; Kahsay, Amaha; Kalani, Hamed; Kalhor, Rohollah; Karami, Manoochehr; Karki, Surendra; Kasaeian, Amir; Kassebaum, Nicholas J; Keiyoro, Peter Njenga; Kemp, Grant Rodgers; Khabiri, Roghayeh; Khader, Yousef Saleh; Khafaie, Morteza Abdullatif; Khan, Ejaz Ahmad; Khan, Junaid; Khan, Muhammad Shahzeb; Khang, Young-Ho; Khatab, Khaled; Khater, Amir; Khater, Mona M; Khatony, Alireza; Khazaei, Mohammad; Khazaei, Salman; Khazaei-Pool, Maryam; Khubchandani, Jagdish; Kianipour, Neda; Kim, Yun Jin; Kimokoti, Ruth W; Kinyoki, Damaris K; Kisa, Adnan; Kisa, Sezer; Kolola, Tufa; Kosen, Soewarta; Koul, Parvaiz A; Koyanagi, Ai; Kraemer, Moritz U G; Krishan, Kewal; Krohn, Kris J; Kugbey, Nuworza; Kumar, G Anil; Kumar, Manasi; Kumar, Pushpendra; Kuupiel, Desmond; Lacey, Ben; Lad, Sheetal D; Lami, Faris Hasan; Larsson, Anders O; Lee, Paul H; Leili, Mostafa; Levine, Aubrey J; Li, Shanshan; Lim, Lee-Ling; Listl, Stefan; Longbottom, Joshua; Lopez, Jaifred Christian F; Lorkowski, Stefan; Magdeldin, Sameh; Abd El Razek, Hassan Magdy; Abd El Razek, Muhammed Magdy; Majeed, Azeem; Maleki, Afshin; Malekzadeh, Reza; Malta, Deborah Carvalho; Mamun, Abdullah A; Manafi, Navid; Manda, Ana-Laura; Mansourian, Morteza; Martins-Melo, Francisco Rogerlândio; Masaka, Anthony; Massenburg, Benjamin Ballard; Maulik, Pallab K; Mayala, Benjamin K; Mazidi, Mohsen; McKee, Martin; Mehrotra, Ravi; Mehta, Kala M; Meles, Gebrekiros Gebremichael; Mendoza, Walter; Menezes, Ritesh G; Meretoja, Atte; Meretoja, Tuomo J; Mestrovic, Tomislav; Miller, Ted R; Miller-Petrie, Molly K; Mills, Edward J; Milne, George J; Mini, G K; Mir, Seyed Mostafa; Mirjalali, Hamed; Mirrakhimov, Erkin M; Mohamadi, Efat; Mohammad, Dara K; Darwesh, Aso Mohammad; Mezerji, Naser Mohammad Gholi; Mohammed, Ammas Siraj; Mohammed, Shafiu; Mokdad, Ali H; Molokhia, Mariam; Monasta, Lorenzo; Moodley, Yoshan; Moosazadeh, Mahmood; Moradi, Ghobad; Moradi, Masoud; Moradi, Yousef; Moradi-Lakeh, Maziar; Moradinazar, Mehdi; Moraga, Paula; Morawska, Lidia; Mosapour, Abbas; Mousavi, Seyyed Meysam; Mueller, Ulrich Otto; Muluneh, Atalay Goshu; Mustafa, Ghulam; Nabavizadeh, Behnam; Naderi, Mehdi; Nagarajan, Ahamarshan Jayaraman; Nahvijou, Azin; Najafi, Farid; Nangia, Vinay; Ndwandwe, Duduzile Edith; Neamati, Nahid; Negoi, Ionut; Negoi, Ruxandra Irina; Ngunjiri, Josephine W; Thi Nguyen, Huong Lan; Nguyen, Long Hoang; Nguyen, Son Hoang; Nielsen, Katie R; Ningrum, Dina Nur Anggraini; Nirayo, Yirga Legesse; Nixon, Molly R; Nnaji, Chukwudi A; Nojomi, Marzieh; Noroozi, Mehdi; Nosratnejad, Shirin; Noubiap, Jean Jacques; Motlagh, Soraya Nouraei; Ofori-Asenso, Richard; Ogbo, Felix Akpojene; Oladimeji, Kelechi E; Olagunju, Andrew T; Olfatifar, Meysam; Olum, Solomon; Olusanya, Bolajoko Olubukunola; Oluwasanu, Mojisola Morenike; Onwujekwe, Obinna E; Oren, Eyal; Ortega-Altamirano, Doris D V; Ortiz, Alberto; Osarenotor, Osayomwanbo; Osei, Frank B; Osgood-Zimmerman, Aaron E; Otstavnov, Stanislav S; Owolabi, Mayowa Ojo; P A, Mahesh; Pagheh, Abdol Sattar; Pakhale, Smita; Panda-Jonas, Songhomitra; Pandey, Animika; Park, Eun-Kee; Parsian, Hadi; Pashaei, Tahereh; Patel, Sangram Kishor; Pepito, Veincent Christian Filipino; Pereira, Alexandre; Perkins, Samantha; Pickering, Brandon V; Pilgrim, Thomas; Pirestani, Majid; Piroozi, Bakhtiar; Pirsaheb, Meghdad; Plana-Ripoll, Oleguer; Pourjafar, Hadi; Puri, Parul; Qorbani, Mostafa; Quintana, Hedley; Rabiee, Mohammad; Rabiee, Navid; Radfar, Amir; Rafiei, Alireza; Rahim, Fakher; Rahimi, Zohreh; Rahimi-Movaghar, Vafa; Rahimzadeh, Shadi; Rajati, Fatemeh; Raju, Sree Bhushan; Ramezankhani, Azra; Ranabhat, Chhabi Lal; Rasella, Davide; Rashedi, Vahid; Rawal, Lal; Reiner, Robert C; Renzaho, Andre M N; Rezaei, Satar; Rezapour, Aziz; Riahi, Seyed Mohammad; Ribeiro, Ana Isabel; Roever, Leonardo; Roro, Elias Merdassa; Roser, Max; Roshandel, Gholamreza; Roshani, Daem; Rostami, Ali; Rubagotti, Enrico; Rubino, Salvatore; Sabour, Siamak; Sadat, Nafis; Sadeghi, Ehsan; Saeedi, Reza; Safari, Yahya; Safari-Faramani, Roya; Safdarian, Mahdi; Sahebkar, Amirhossein; Salahshoor, Mohammad Reza; Salam, Nasir; Salamati, Payman; Salehi, Farkhonde; Zahabi, Saleh Salehi; Salimi, Yahya; Salimzadeh, Hamideh; Salomon, Joshua A; Sambala, Evanson Zondani; Samy, Abdallah M; Santric Milicevic, Milena M; Jose, Bruno Piassi Sao; Saraswathy, Sivan Yegnanarayana Iyer; Sarmiento-Suárez, Rodrigo; Sartorius, Benn; Sathian, Brijesh; Saxena, Sonia; Sbarra, Alyssa N; Schaeffer, Lauren E; Schwebel, David C; Sepanlou, Sadaf G; Seyedmousavi, Seyedmojtaba; Shaahmadi, Faramarz; Shaikh, Masood Ali; Shams-Beyranvand, Mehran; Shamshirian, Amir; Shamsizadeh, Morteza; Sharafi, Kiomars; Sharif, Mehdi; Sharif-Alhoseini, Mahdi; Sharifi, Hamid; Sharma, Jayendra; Sharma, Rajesh; Sheikh, Aziz; Shields, Chloe; Shigematsu, Mika; Shiri, Rahman; Shiue, Ivy; Shuval, Kerem; Siddiqi, Tariq J; Silva, João Pedro; Singh, Jasvinder A; Sinha, Dhirendra Narain; Sisay, Malede Mequanent; Sisay, Solomon; Sliwa, Karen; Smith, David L; Somayaji, Ranjani; Soofi, Moslem; Soriano, Joan B; Sreeramareddy, Chandrashekhar T; Sudaryanto, Agus; Sufiyan, Mu'awiyyah Babale; Sykes, Bryan L; Sylaja, P N; Tabarés-Seisdedos, Rafael; Tabb, Karen M; Tabuchi, Takahiro; Taveira, Nuno; Temsah, Mohamad-Hani; Terkawi, Abdullah Sulieman; Tessema, Zemenu Tadesse; Thankappan, Kavumpurathu Raman; Thirunavukkarasu, Sathish; To, Quyen G; Tovani-Palone, Marcos Roberto; Tran, Bach Xuan; Tran, Khanh Bao; Ullah, Irfan; Usman, Muhammad Shariq; Uthman, Olalekan A; Vahedian-Azimi, Amir; Valdez, Pascual R; van Boven, Job F M; Vasankari, Tommi Juhani; Vasseghian, Yasser; Veisani, Yousef; Venketasubramanian, Narayanaswamy; Violante, Francesco S; Vladimirov, Sergey Konstantinovitch; Vlassov, Vasily; Vos, Theo; Vu, Giang Thu; Vujcic, Isidora S; Waheed, Yasir; Wakefield, Jon; Wang, Haidong; Wang, Yafeng; Wang, Yuan-Pang; Ward, Joseph L; Weintraub, Robert G; Weldegwergs, Kidu Gidey; Weldesamuel, Girmay Teklay; Westerman, Ronny; Wiysonge, Charles Shey; Wondafrash, Dawit Zewdu; Woyczynski, Lauren; Wu, Ai-Min; Xu, Gelin; Yadegar, Abbas; Yamada, Tomohide; Yazdi-Feyzabadi, Vahid; Yilgwan, Christopher Sabo; Yip, Paul; Yonemoto, Naohiro; Lebni, Javad Yoosefi; Younis, Mustafa Z; Yousefifard, Mahmoud; Yousof, Hebat-Allah Salah A; Yu, Chuanhua; Yusefzadeh, Hasan; Zabeh, Erfan; Moghadam, Telma Zahirian; Bin Zaman, Sojib; Zamani, Mohammad; Zandian, Hamed; Zangeneh, Alireza; Zerfu, Taddese Alemu; Zhang, Yunquan; Ziapour, Arash; Zodpey, Sanjay; Murray, Christopher J L; Hay, Simon I
Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2-to end preventable child deaths by 2030-we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000-2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.
PMID: 31619795
ISSN: 1476-4687
CID: 5831902