TY - JOUR
T1 - Genetic loci associated with heart rate variability and their effects on cardiac disease risk.
JF - Nat Commun
Y1 - 2017
A1 - Nolte, Ilja M
A1 - Munoz, M Loretto
A1 - Tragante, Vinicius
A1 - Amare, Azmeraw T
A1 - Jansen, Rick
A1 - Vaez, Ahmad
A1 - von der Heyde, Benedikt
A1 - Avery, Christy L
A1 - Bis, Joshua C
A1 - Dierckx, Bram
A1 - van Dongen, Jenny
A1 - Gogarten, Stephanie M
A1 - Goyette, Philippe
A1 - Hernesniemi, Jussi
A1 - Huikari, Ville
A1 - Hwang, Shih-Jen
A1 - Jaju, Deepali
A1 - Kerr, Kathleen F
A1 - Kluttig, Alexander
A1 - Krijthe, Bouwe P
A1 - Kumar, Jitender
A1 - van der Laan, Sander W
A1 - Lyytikäinen, Leo-Pekka
A1 - Maihofer, Adam X
A1 - Minassian, Arpi
A1 - van der Most, Peter J
A1 - Müller-Nurasyid, Martina
A1 - Nivard, Michel
A1 - Salvi, Erika
A1 - Stewart, James D
A1 - Thayer, Julian F
A1 - Verweij, Niek
A1 - Wong, Andrew
A1 - Zabaneh, Delilah
A1 - Zafarmand, Mohammad H
A1 - Abdellaoui, Abdel
A1 - Albarwani, Sulayma
A1 - Albert, Christine
A1 - Alonso, Alvaro
A1 - Ashar, Foram
A1 - Auvinen, Juha
A1 - Axelsson, Tomas
A1 - Baker, Dewleen G
A1 - de Bakker, Paul I W
A1 - Barcella, Matteo
A1 - Bayoumi, Riad
A1 - Bieringa, Rob J
A1 - Boomsma, Dorret
A1 - Boucher, Gabrielle
A1 - Britton, Annie R
A1 - Christophersen, Ingrid
A1 - Dietrich, Andrea
A1 - Ehret, George B
A1 - Ellinor, Patrick T
A1 - Eskola, Markku
A1 - Felix, Janine F
A1 - Floras, John S
A1 - Franco, Oscar H
A1 - Friberg, Peter
A1 - Gademan, Maaike G J
A1 - Geyer, Mark A
A1 - Giedraitis, Vilmantas
A1 - Hartman, Catharina A
A1 - Hemerich, Daiane
A1 - Hofman, Albert
A1 - Hottenga, Jouke-Jan
A1 - Huikuri, Heikki
A1 - Hutri-Kähönen, Nina
A1 - Jouven, Xavier
A1 - Junttila, Juhani
A1 - Juonala, Markus
A1 - Kiviniemi, Antti M
A1 - Kors, Jan A
A1 - Kumari, Meena
A1 - Kuznetsova, Tatiana
A1 - Laurie, Cathy C
A1 - Lefrandt, Joop D
A1 - Li, Yong
A1 - Li, Yun
A1 - Liao, Duanping
A1 - Limacher, Marian C
A1 - Lin, Henry J
A1 - Lindgren, Cecilia M
A1 - Lubitz, Steven A
A1 - Mahajan, Anubha
A1 - McKnight, Barbara
A1 - Zu Schwabedissen, Henriette Meyer
A1 - Milaneschi, Yuri
A1 - Mononen, Nina
A1 - Morris, Andrew P
A1 - Nalls, Mike A
A1 - Navis, Gerjan
A1 - Neijts, Melanie
A1 - Nikus, Kjell
A1 - North, Kari E
A1 - O'Connor, Daniel T
A1 - Ormel, Johan
A1 - Perz, Siegfried
A1 - Peters, Annette
A1 - Psaty, Bruce M
A1 - Raitakari, Olli T
A1 - Risbrough, Victoria B
A1 - Sinner, Moritz F
A1 - Siscovick, David
A1 - Smit, Johannes H
A1 - Smith, Nicholas L
A1 - Soliman, Elsayed Z
A1 - Sotoodehnia, Nona
A1 - Staessen, Jan A
A1 - Stein, Phyllis K
A1 - Stilp, Adrienne M
A1 - Stolarz-Skrzypek, Katarzyna
A1 - Strauch, Konstantin
A1 - Sundström, Johan
A1 - Swenne, Cees A
A1 - Syvänen, Ann-Christine
A1 - Tardif, Jean-Claude
A1 - Taylor, Kent D
A1 - Teumer, Alexander
A1 - Thornton, Timothy A
A1 - Tinker, Lesley E
A1 - Uitterlinden, André G
A1 - van Setten, Jessica
A1 - Voss, Andreas
A1 - Waldenberger, Melanie
A1 - Wilhelmsen, Kirk C
A1 - Willemsen, Gonneke
A1 - Wong, Quenna
A1 - Zhang, Zhu-Ming
A1 - Zonderman, Alan B
A1 - Cusi, Daniele
A1 - Evans, Michele K
A1 - Greiser, Halina K
A1 - van der Harst, Pim
A1 - Hassan, Mohammad
A1 - Ingelsson, Erik
A1 - Jarvelin, Marjo-Riitta
A1 - Kääb, Stefan
A1 - Kähönen, Mika
A1 - Kivimaki, Mika
A1 - Kooperberg, Charles
A1 - Kuh, Diana
A1 - Lehtimäki, Terho
A1 - Lind, Lars
A1 - Nievergelt, Caroline M
A1 - O'Donnell, Chris J
A1 - Oldehinkel, Albertine J
A1 - Penninx, Brenda
A1 - Reiner, Alexander P
A1 - Riese, Harriëtte
A1 - van Roon, Arie M
A1 - Rioux, John D
A1 - Rotter, Jerome I
A1 - Sofer, Tamar
A1 - Stricker, Bruno H
A1 - Tiemeier, Henning
A1 - Vrijkotte, Tanja G M
A1 - Asselbergs, Folkert W
A1 - Brundel, Bianca J J M
A1 - Heckbert, Susan R
A1 - Whitsel, Eric A
A1 - den Hoed, Marcel
A1 - Snieder, Harold
A1 - de Geus, Eco J C
AB -
Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74
VL - 8
ER -
TY - JOUR
T1 - A catalog of genetic loci associated with kidney function from analyses of a million individuals.
JF - Nat Genet
Y1 - 2019
A1 - Wuttke, Matthias
A1 - Li, Yong
A1 - Li, Man
A1 - Sieber, Karsten B
A1 - Feitosa, Mary F
A1 - Gorski, Mathias
A1 - Tin, Adrienne
A1 - Wang, Lihua
A1 - Chu, Audrey Y
A1 - Hoppmann, Anselm
A1 - Kirsten, Holger
A1 - Giri, Ayush
A1 - Chai, Jin-Fang
A1 - Sveinbjornsson, Gardar
A1 - Tayo, Bamidele O
A1 - Nutile, Teresa
A1 - Fuchsberger, Christian
A1 - Marten, Jonathan
A1 - Cocca, Massimiliano
A1 - Ghasemi, Sahar
A1 - Xu, Yizhe
A1 - Horn, Katrin
A1 - Noce, Damia
A1 - van der Most, Peter J
A1 - Sedaghat, Sanaz
A1 - Yu, Zhi
A1 - Akiyama, Masato
A1 - Afaq, Saima
A1 - Ahluwalia, Tarunveer S
A1 - Almgren, Peter
A1 - Amin, Najaf
A1 - Arnlöv, Johan
A1 - Bakker, Stephan J L
A1 - Bansal, Nisha
A1 - Baptista, Daniela
A1 - Bergmann, Sven
A1 - Biggs, Mary L
A1 - Biino, Ginevra
A1 - Boehnke, Michael
A1 - Boerwinkle, Eric
A1 - Boissel, Mathilde
A1 - Bottinger, Erwin P
A1 - Boutin, Thibaud S
A1 - Brenner, Hermann
A1 - Brumat, Marco
A1 - Burkhardt, Ralph
A1 - Butterworth, Adam S
A1 - Campana, Eric
A1 - Campbell, Archie
A1 - Campbell, Harry
A1 - Canouil, Mickaël
A1 - Carroll, Robert J
A1 - Catamo, Eulalia
A1 - Chambers, John C
A1 - Chee, Miao-Ling
A1 - Chee, Miao-Li
A1 - Chen, Xu
A1 - Cheng, Ching-Yu
A1 - Cheng, Yurong
A1 - Christensen, Kaare
A1 - Cifkova, Renata
A1 - Ciullo, Marina
A1 - Concas, Maria Pina
A1 - Cook, James P
A1 - Coresh, Josef
A1 - Corre, Tanguy
A1 - Sala, Cinzia Felicita
A1 - Cusi, Daniele
A1 - Danesh, John
A1 - Daw, E Warwick
A1 - de Borst, Martin H
A1 - De Grandi, Alessandro
A1 - de Mutsert, Renée
A1 - de Vries, Aiko P J
A1 - Degenhardt, Frauke
A1 - Delgado, Graciela
A1 - Demirkan, Ayse
A1 - Di Angelantonio, Emanuele
A1 - Dittrich, Katalin
A1 - Divers, Jasmin
A1 - Dorajoo, Rajkumar
A1 - Eckardt, Kai-Uwe
A1 - Ehret, Georg
A1 - Elliott, Paul
A1 - Endlich, Karlhans
A1 - Evans, Michele K
A1 - Felix, Janine F
A1 - Foo, Valencia Hui Xian
A1 - Franco, Oscar H
A1 - Franke, Andre
A1 - Freedman, Barry I
A1 - Freitag-Wolf, Sandra
A1 - Friedlander, Yechiel
A1 - Froguel, Philippe
A1 - Gansevoort, Ron T
A1 - Gao, He
A1 - Gasparini, Paolo
A1 - Gaziano, J Michael
A1 - Giedraitis, Vilmantas
A1 - Gieger, Christian
A1 - Girotto, Giorgia
A1 - Giulianini, Franco
A1 - Gögele, Martin
A1 - Gordon, Scott D
A1 - Gudbjartsson, Daniel F
A1 - Gudnason, Vilmundur
A1 - Haller, Toomas
A1 - Hamet, Pavel
A1 - Harris, Tamara B
A1 - Hartman, Catharina A
A1 - Hayward, Caroline
A1 - Hellwege, Jacklyn N
A1 - Heng, Chew-Kiat
A1 - Hicks, Andrew A
A1 - Hofer, Edith
A1 - Huang, Wei
A1 - Hutri-Kähönen, Nina
A1 - Hwang, Shih-Jen
A1 - Ikram, M Arfan
A1 - Indridason, Olafur S
A1 - Ingelsson, Erik
A1 - Ising, Marcus
A1 - Jaddoe, Vincent W V
A1 - Jakobsdottir, Johanna
A1 - Jonas, Jost B
A1 - Joshi, Peter K
A1 - Josyula, Navya Shilpa
A1 - Jung, Bettina
A1 - Kähönen, Mika
A1 - Kamatani, Yoichiro
A1 - Kammerer, Candace M
A1 - Kanai, Masahiro
A1 - Kastarinen, Mika
A1 - Kerr, Shona M
A1 - Khor, Chiea-Chuen
A1 - Kiess, Wieland
A1 - Kleber, Marcus E
A1 - Koenig, Wolfgang
A1 - Kooner, Jaspal S
A1 - Körner, Antje
A1 - Kovacs, Peter
A1 - Kraja, Aldi T
A1 - Krajcoviechova, Alena
A1 - Kramer, Holly
A1 - Krämer, Bernhard K
A1 - Kronenberg, Florian
A1 - Kubo, Michiaki
A1 - Kuhnel, Brigitte
A1 - Kuokkanen, Mikko
A1 - Kuusisto, Johanna
A1 - La Bianca, Martina
A1 - Laakso, Markku
A1 - Lange, Leslie A
A1 - Langefeld, Carl D
A1 - Lee, Jeannette Jen-Mai
A1 - Lehne, Benjamin
A1 - Lehtimäki, Terho
A1 - Lieb, Wolfgang
A1 - Lim, Su-Chi
A1 - Lind, Lars
A1 - Lindgren, Cecilia M
A1 - Liu, Jun
A1 - Liu, Jianjun
A1 - Loeffler, Markus
A1 - Loos, Ruth J F
A1 - Lucae, Susanne
A1 - Lukas, Mary Ann
A1 - Lyytikäinen, Leo-Pekka
A1 - Mägi, Reedik
A1 - Magnusson, Patrik K E
A1 - Mahajan, Anubha
A1 - Martin, Nicholas G
A1 - Martins, Jade
A1 - März, Winfried
A1 - Mascalzoni, Deborah
A1 - Matsuda, Koichi
A1 - Meisinger, Christa
A1 - Meitinger, Thomas
A1 - Melander, Olle
A1 - Metspalu, Andres
A1 - Mikaelsdottir, Evgenia K
A1 - Milaneschi, Yuri
A1 - Miliku, Kozeta
A1 - Mishra, Pashupati P
A1 - Mohlke, Karen L
A1 - Mononen, Nina
A1 - Montgomery, Grant W
A1 - Mook-Kanamori, Dennis O
A1 - Mychaleckyj, Josyf C
A1 - Nadkarni, Girish N
A1 - Nalls, Mike A
A1 - Nauck, Matthias
A1 - Nikus, Kjell
A1 - Ning, Boting
A1 - Nolte, Ilja M
A1 - Noordam, Raymond
A1 - O'Connell, Jeffrey
A1 - O'Donoghue, Michelle L
A1 - Olafsson, Isleifur
A1 - Oldehinkel, Albertine J
A1 - Orho-Melander, Marju
A1 - Ouwehand, Willem H
A1 - Padmanabhan, Sandosh
A1 - Palmer, Nicholette D
A1 - Palsson, Runolfur
A1 - Penninx, Brenda W J H
A1 - Perls, Thomas
A1 - Perola, Markus
A1 - Pirastu, Mario
A1 - Pirastu, Nicola
A1 - Pistis, Giorgio
A1 - Podgornaia, Anna I
A1 - Polasek, Ozren
A1 - Ponte, Belen
A1 - Porteous, David J
A1 - Poulain, Tanja
A1 - Pramstaller, Peter P
A1 - Preuss, Michael H
A1 - Prins, Bram P
A1 - Province, Michael A
A1 - Rabelink, Ton J
A1 - Raffield, Laura M
A1 - Raitakari, Olli T
A1 - Reilly, Dermot F
A1 - Rettig, Rainer
A1 - Rheinberger, Myriam
A1 - Rice, Kenneth M
A1 - Ridker, Paul M
A1 - Rivadeneira, Fernando
A1 - Rizzi, Federica
A1 - Roberts, David J
A1 - Robino, Antonietta
A1 - Rossing, Peter
A1 - Rudan, Igor
A1 - Rueedi, Rico
A1 - Ruggiero, Daniela
A1 - Ryan, Kathleen A
A1 - Saba, Yasaman
A1 - Sabanayagam, Charumathi
A1 - Salomaa, Veikko
A1 - Salvi, Erika
A1 - Saum, Kai-Uwe
A1 - Schmidt, Helena
A1 - Schmidt, Reinhold
A1 - Schöttker, Ben
A1 - Schulz, Christina-Alexandra
A1 - Schupf, Nicole
A1 - Shaffer, Christian M
A1 - Shi, Yuan
A1 - Smith, Albert V
A1 - Smith, Blair H
A1 - Soranzo, Nicole
A1 - Spracklen, Cassandra N
A1 - Strauch, Konstantin
A1 - Stringham, Heather M
A1 - Stumvoll, Michael
A1 - Svensson, Per O
A1 - Szymczak, Silke
A1 - Tai, E-Shyong
A1 - Tajuddin, Salman M
A1 - Tan, Nicholas Y Q
A1 - Taylor, Kent D
A1 - Teren, Andrej
A1 - Tham, Yih-Chung
A1 - Thiery, Joachim
A1 - Thio, Chris H L
A1 - Thomsen, Hauke
A1 - Thorleifsson, Gudmar
A1 - Toniolo, Daniela
A1 - Tönjes, Anke
A1 - Tremblay, Johanne
A1 - Tzoulaki, Ioanna
A1 - Uitterlinden, André G
A1 - Vaccargiu, Simona
A1 - van Dam, Rob M
A1 - van der Harst, Pim
A1 - van Duijn, Cornelia M
A1 - Velez Edward, Digna R
A1 - Verweij, Niek
A1 - Vogelezang, Suzanne
A1 - Völker, Uwe
A1 - Vollenweider, Peter
A1 - Waeber, Gérard
A1 - Waldenberger, Melanie
A1 - Wallentin, Lars
A1 - Wang, Ya Xing
A1 - Wang, Chaolong
A1 - Waterworth, Dawn M
A1 - Bin Wei, Wen
A1 - White, Harvey
A1 - Whitfield, John B
A1 - Wild, Sarah H
A1 - Wilson, James F
A1 - Wojczynski, Mary K
A1 - Wong, Charlene
A1 - Wong, Tien-Yin
A1 - Xu, Liang
A1 - Yang, Qiong
A1 - Yasuda, Masayuki
A1 - Yerges-Armstrong, Laura M
A1 - Zhang, Weihua
A1 - Zonderman, Alan B
A1 - Rotter, Jerome I
A1 - Bochud, Murielle
A1 - Psaty, Bruce M
A1 - Vitart, Veronique
A1 - Wilson, James G
A1 - Dehghan, Abbas
A1 - Parsa, Afshin
A1 - Chasman, Daniel I
A1 - Ho, Kevin
A1 - Morris, Andrew P
A1 - Devuyst, Olivier
A1 - Akilesh, Shreeram
A1 - Pendergrass, Sarah A
A1 - Sim, Xueling
A1 - Böger, Carsten A
A1 - Okada, Yukinori
A1 - Edwards, Todd L
A1 - Snieder, Harold
A1 - Stefansson, Kari
A1 - Hung, Adriana M
A1 - Heid, Iris M
A1 - Scholz, Markus
A1 - Teumer, Alexander
A1 - Köttgen, Anna
A1 - Pattaro, Cristian
KW - Chromosome Mapping
KW - European Continental Ancestry Group
KW - Genetic Association Studies
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Glomerular Filtration Rate
KW - Humans
KW - Inheritance Patterns
KW - Kidney Function Tests
KW - Phenotype
KW - Polymorphism, Single Nucleotide
KW - Quantitative Trait Loci
KW - Quantitative Trait, Heritable
KW - Renal Insufficiency, Chronic
KW - Uromodulin
AB - Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry 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.
VL - 51
IS - 6
ER -
TY - JOUR
T1 - Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.
JF - Nat Genet
Y1 - 2019
A1 - Tin, Adrienne
A1 - Marten, Jonathan
A1 - Halperin Kuhns, Victoria L
A1 - Li, Yong
A1 - Wuttke, Matthias
A1 - Kirsten, Holger
A1 - Sieber, Karsten B
A1 - Qiu, Chengxiang
A1 - Gorski, Mathias
A1 - Yu, Zhi
A1 - Giri, Ayush
A1 - Sveinbjornsson, Gardar
A1 - Li, Man
A1 - Chu, Audrey Y
A1 - Hoppmann, Anselm
A1 - O'Connor, Luke J
A1 - Prins, Bram
A1 - Nutile, Teresa
A1 - Noce, Damia
A1 - Akiyama, Masato
A1 - Cocca, Massimiliano
A1 - Ghasemi, Sahar
A1 - van der Most, Peter J
A1 - Horn, Katrin
A1 - Xu, Yizhe
A1 - Fuchsberger, Christian
A1 - Sedaghat, Sanaz
A1 - Afaq, Saima
A1 - Amin, Najaf
A1 - Arnlöv, Johan
A1 - Bakker, Stephan J L
A1 - Bansal, Nisha
A1 - Baptista, Daniela
A1 - Bergmann, Sven
A1 - Biggs, Mary L
A1 - Biino, Ginevra
A1 - Boerwinkle, Eric
A1 - Bottinger, Erwin P
A1 - Boutin, Thibaud S
A1 - Brumat, Marco
A1 - Burkhardt, Ralph
A1 - Campana, Eric
A1 - Campbell, Archie
A1 - Campbell, Harry
A1 - Carroll, Robert J
A1 - Catamo, Eulalia
A1 - Chambers, John C
A1 - Ciullo, Marina
A1 - Concas, Maria Pina
A1 - Coresh, Josef
A1 - Corre, Tanguy
A1 - Cusi, Daniele
A1 - Felicita, Sala Cinzia
A1 - de Borst, Martin H
A1 - De Grandi, Alessandro
A1 - de Mutsert, Renée
A1 - de Vries, Aiko P J
A1 - Delgado, Graciela
A1 - Demirkan, Ayse
A1 - Devuyst, Olivier
A1 - Dittrich, Katalin
A1 - Eckardt, Kai-Uwe
A1 - Ehret, Georg
A1 - Endlich, Karlhans
A1 - Evans, Michele K
A1 - Gansevoort, Ron T
A1 - Gasparini, Paolo
A1 - Giedraitis, Vilmantas
A1 - Gieger, Christian
A1 - Girotto, Giorgia
A1 - Gögele, Martin
A1 - Gordon, Scott D
A1 - Gudbjartsson, Daniel F
A1 - Gudnason, Vilmundur
A1 - Haller, Toomas
A1 - Hamet, Pavel
A1 - Harris, Tamara B
A1 - Hayward, Caroline
A1 - Hicks, Andrew A
A1 - Hofer, Edith
A1 - Holm, Hilma
A1 - Huang, Wei
A1 - Hutri-Kähönen, Nina
A1 - Hwang, Shih-Jen
A1 - Ikram, M Arfan
A1 - Lewis, Raychel M
A1 - Ingelsson, Erik
A1 - Jakobsdottir, Johanna
A1 - Jonsdottir, Ingileif
A1 - Jonsson, Helgi
A1 - Joshi, Peter K
A1 - Josyula, Navya Shilpa
A1 - Jung, Bettina
A1 - Kähönen, Mika
A1 - Kamatani, Yoichiro
A1 - Kanai, Masahiro
A1 - Kerr, Shona M
A1 - Kiess, Wieland
A1 - Kleber, Marcus E
A1 - Koenig, Wolfgang
A1 - Kooner, Jaspal S
A1 - Körner, Antje
A1 - Kovacs, Peter
A1 - Krämer, Bernhard K
A1 - Kronenberg, Florian
A1 - Kubo, Michiaki
A1 - Kuhnel, Brigitte
A1 - La Bianca, Martina
A1 - Lange, Leslie A
A1 - Lehne, Benjamin
A1 - Lehtimäki, Terho
A1 - Liu, Jun
A1 - Loeffler, Markus
A1 - Loos, Ruth J F
A1 - Lyytikäinen, Leo-Pekka
A1 - Mägi, Reedik
A1 - Mahajan, Anubha
A1 - Martin, Nicholas G
A1 - März, Winfried
A1 - Mascalzoni, Deborah
A1 - Matsuda, Koichi
A1 - Meisinger, Christa
A1 - Meitinger, Thomas
A1 - Metspalu, Andres
A1 - Milaneschi, Yuri
A1 - O'Donnell, Christopher J
A1 - Wilson, Otis D
A1 - Gaziano, J Michael
A1 - Mishra, Pashupati P
A1 - Mohlke, Karen L
A1 - Mononen, Nina
A1 - Montgomery, Grant W
A1 - Mook-Kanamori, Dennis O
A1 - Müller-Nurasyid, Martina
A1 - Nadkarni, Girish N
A1 - Nalls, Mike A
A1 - Nauck, Matthias
A1 - Nikus, Kjell
A1 - Ning, Boting
A1 - Nolte, Ilja M
A1 - Noordam, Raymond
A1 - O'Connell, Jeffrey R
A1 - Olafsson, Isleifur
A1 - Padmanabhan, Sandosh
A1 - Penninx, Brenda W J H
A1 - Perls, Thomas
A1 - Peters, Annette
A1 - Pirastu, Mario
A1 - Pirastu, Nicola
A1 - Pistis, Giorgio
A1 - Polasek, Ozren
A1 - Ponte, Belen
A1 - Porteous, David J
A1 - Poulain, Tanja
A1 - Preuss, Michael H
A1 - Rabelink, Ton J
A1 - Raffield, Laura M
A1 - Raitakari, Olli T
A1 - Rettig, Rainer
A1 - Rheinberger, Myriam
A1 - Rice, Kenneth M
A1 - Rizzi, Federica
A1 - Robino, Antonietta
A1 - Rudan, Igor
A1 - Krajcoviechova, Alena
A1 - Cifkova, Renata
A1 - Rueedi, Rico
A1 - Ruggiero, Daniela
A1 - Ryan, Kathleen A
A1 - Saba, Yasaman
A1 - Salvi, Erika
A1 - Schmidt, Helena
A1 - Schmidt, Reinhold
A1 - Shaffer, Christian M
A1 - Smith, Albert V
A1 - Smith, Blair H
A1 - Spracklen, Cassandra N
A1 - Strauch, Konstantin
A1 - Stumvoll, Michael
A1 - Sulem, Patrick
A1 - Tajuddin, Salman M
A1 - Teren, Andrej
A1 - Thiery, Joachim
A1 - Thio, Chris H L
A1 - Thorsteinsdottir, Unnur
A1 - Toniolo, Daniela
A1 - Tönjes, Anke
A1 - Tremblay, Johanne
A1 - Uitterlinden, André G
A1 - Vaccargiu, Simona
A1 - van der Harst, Pim
A1 - van Duijn, Cornelia M
A1 - Verweij, Niek
A1 - Völker, Uwe
A1 - Vollenweider, Peter
A1 - Waeber, Gérard
A1 - Waldenberger, Melanie
A1 - Whitfield, John B
A1 - Wild, Sarah H
A1 - Wilson, James F
A1 - Yang, Qiong
A1 - Zhang, Weihua
A1 - Zonderman, Alan B
A1 - Bochud, Murielle
A1 - Wilson, James G
A1 - Pendergrass, Sarah A
A1 - Ho, Kevin
A1 - Parsa, Afshin
A1 - Pramstaller, Peter P
A1 - Psaty, Bruce M
A1 - Böger, Carsten A
A1 - Snieder, Harold
A1 - Butterworth, Adam S
A1 - Okada, Yukinori
A1 - Edwards, Todd L
A1 - Stefansson, Kari
A1 - Susztak, Katalin
A1 - Scholz, Markus
A1 - Heid, Iris M
A1 - Hung, Adriana M
A1 - Teumer, Alexander
A1 - Pattaro, Cristian
A1 - Woodward, Owen M
A1 - Vitart, Veronique
A1 - Köttgen, Anna
AB - 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.
VL - 51
IS - 10
ER -
TY - JOUR
T1 - Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline.
JF - Kidney Int
Y1 - 2020
A1 - Gorski, Mathias
A1 - Jung, Bettina
A1 - Li, Yong
A1 - Matias-Garcia, Pamela R
A1 - Wuttke, Matthias
A1 - Coassin, Stefan
A1 - Thio, Chris H L
A1 - Kleber, Marcus E
A1 - Winkler, Thomas W
A1 - Wanner, Veronika
A1 - Chai, Jin-Fang
A1 - Chu, Audrey Y
A1 - Cocca, Massimiliano
A1 - Feitosa, Mary F
A1 - Ghasemi, Sahar
A1 - Hoppmann, Anselm
A1 - Horn, Katrin
A1 - Li, Man
A1 - Nutile, Teresa
A1 - Scholz, Markus
A1 - Sieber, Karsten B
A1 - Teumer, Alexander
A1 - Tin, Adrienne
A1 - Wang, Judy
A1 - Tayo, Bamidele O
A1 - Ahluwalia, Tarunveer S
A1 - Almgren, Peter
A1 - Bakker, Stephan J L
A1 - Banas, Bernhard
A1 - Bansal, Nisha
A1 - Biggs, Mary L
A1 - Boerwinkle, Eric
A1 - Bottinger, Erwin P
A1 - Brenner, Hermann
A1 - Carroll, Robert J
A1 - Chalmers, John
A1 - Chee, Miao-Li
A1 - Chee, Miao-Ling
A1 - Cheng, Ching-Yu
A1 - Coresh, Josef
A1 - de Borst, Martin H
A1 - Degenhardt, Frauke
A1 - Eckardt, Kai-Uwe
A1 - Endlich, Karlhans
A1 - Franke, Andre
A1 - Freitag-Wolf, Sandra
A1 - Gampawar, Piyush
A1 - Gansevoort, Ron T
A1 - Ghanbari, Mohsen
A1 - Gieger, Christian
A1 - Hamet, Pavel
A1 - Ho, Kevin
A1 - Hofer, Edith
A1 - Holleczek, Bernd
A1 - Xian Foo, Valencia Hui
A1 - Hutri-Kähönen, Nina
A1 - Hwang, Shih-Jen
A1 - Ikram, M Arfan
A1 - Josyula, Navya Shilpa
A1 - Kähönen, Mika
A1 - Khor, Chiea-Chuen
A1 - Koenig, Wolfgang
A1 - Kramer, Holly
A1 - Krämer, Bernhard K
A1 - Kuhnel, Brigitte
A1 - Lange, Leslie A
A1 - Lehtimäki, Terho
A1 - Lieb, Wolfgang
A1 - Loos, Ruth J F
A1 - Lukas, Mary Ann
A1 - Lyytikäinen, Leo-Pekka
A1 - Meisinger, Christa
A1 - Meitinger, Thomas
A1 - Melander, Olle
A1 - Milaneschi, Yuri
A1 - Mishra, Pashupati P
A1 - Mononen, Nina
A1 - Mychaleckyj, Josyf C
A1 - Nadkarni, Girish N
A1 - Nauck, Matthias
A1 - Nikus, Kjell
A1 - Ning, Boting
A1 - Nolte, Ilja M
A1 - O'Donoghue, Michelle L
A1 - Orho-Melander, Marju
A1 - Pendergrass, Sarah A
A1 - Penninx, Brenda W J H
A1 - Preuss, Michael H
A1 - Psaty, Bruce M
A1 - Raffield, Laura M
A1 - Raitakari, Olli T
A1 - Rettig, Rainer
A1 - Rheinberger, Myriam
A1 - Rice, Kenneth M
A1 - Rosenkranz, Alexander R
A1 - Rossing, Peter
A1 - Rotter, Jerome I
A1 - Sabanayagam, Charumathi
A1 - Schmidt, Helena
A1 - Schmidt, Reinhold
A1 - Schöttker, Ben
A1 - Schulz, Christina-Alexandra
A1 - Sedaghat, Sanaz
A1 - Shaffer, Christian M
A1 - Strauch, Konstantin
A1 - Szymczak, Silke
A1 - Taylor, Kent D
A1 - Tremblay, Johanne
A1 - Chaker, Layal
A1 - van der Harst, Pim
A1 - van der Most, Peter J
A1 - Verweij, Niek
A1 - Völker, Uwe
A1 - Waldenberger, Melanie
A1 - Wallentin, Lars
A1 - Waterworth, Dawn M
A1 - White, Harvey D
A1 - Wilson, James G
A1 - Wong, Tien-Yin
A1 - Woodward, Mark
A1 - Yang, Qiong
A1 - Yasuda, Masayuki
A1 - Yerges-Armstrong, Laura M
A1 - Zhang, Yan
A1 - Snieder, Harold
A1 - Wanner, Christoph
A1 - Böger, Carsten A
A1 - Köttgen, Anna
A1 - Kronenberg, Florian
A1 - Pattaro, Cristian
A1 - Heid, Iris M
AB - Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m at follow-up among those with eGFRcrea 60 mL/min/1.73m or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
ER -
TY - JOUR
T1 - Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.
JF - Nat Commun
Y1 - 2020
A1 - Ntalla, Ioanna
A1 - Weng, Lu-Chen
A1 - Cartwright, James H
A1 - Hall, Amelia Weber
A1 - Sveinbjornsson, Gardar
A1 - Tucker, Nathan R
A1 - Choi, Seung Hoan
A1 - Chaffin, Mark D
A1 - Roselli, Carolina
A1 - Barnes, Michael R
A1 - Mifsud, Borbala
A1 - Warren, Helen R
A1 - Hayward, Caroline
A1 - Marten, Jonathan
A1 - Cranley, James J
A1 - Concas, Maria Pina
A1 - Gasparini, Paolo
A1 - Boutin, Thibaud
A1 - Kolcic, Ivana
A1 - Polasek, Ozren
A1 - Rudan, Igor
A1 - Araujo, Nathalia M
A1 - Lima-Costa, Maria Fernanda
A1 - Ribeiro, Antonio Luiz P
A1 - Souza, Renan P
A1 - Tarazona-Santos, Eduardo
A1 - Giedraitis, Vilmantas
A1 - Ingelsson, Erik
A1 - Mahajan, Anubha
A1 - Morris, Andrew P
A1 - del Greco M, Fabiola
A1 - Foco, Luisa
A1 - Gögele, Martin
A1 - Hicks, Andrew A
A1 - Cook, James P
A1 - Lind, Lars
A1 - Lindgren, Cecilia M
A1 - Sundström, Johan
A1 - Nelson, Christopher P
A1 - Riaz, Muhammad B
A1 - Samani, Nilesh J
A1 - Sinagra, Gianfranco
A1 - Ulivi, Sheila
A1 - Kähönen, Mika
A1 - Mishra, Pashupati P
A1 - Mononen, Nina
A1 - Nikus, Kjell
A1 - Caulfield, Mark J
A1 - Dominiczak, Anna
A1 - Padmanabhan, Sandosh
A1 - Montasser, May E
A1 - O'Connell, Jeff R
A1 - Ryan, Kathleen
A1 - Shuldiner, Alan R
A1 - Aeschbacher, Stefanie
A1 - Conen, David
A1 - Risch, Lorenz
A1 - Thériault, Sébastien
A1 - Hutri-Kähönen, Nina
A1 - Lehtimäki, Terho
A1 - Lyytikäinen, Leo-Pekka
A1 - Raitakari, Olli T
A1 - Barnes, Catriona L K
A1 - Campbell, Harry
A1 - Joshi, Peter K
A1 - Wilson, James F
A1 - Isaacs, Aaron
A1 - Kors, Jan A
A1 - van Duijn, Cornelia M
A1 - Huang, Paul L
A1 - Gudnason, Vilmundur
A1 - Harris, Tamara B
A1 - Launer, Lenore J
A1 - Smith, Albert V
A1 - Bottinger, Erwin P
A1 - Loos, Ruth J F
A1 - Nadkarni, Girish N
A1 - Preuss, Michael H
A1 - Correa, Adolfo
A1 - Mei, Hao
A1 - Wilson, James
A1 - Meitinger, Thomas
A1 - Müller-Nurasyid, Martina
A1 - Peters, Annette
A1 - Waldenberger, Melanie
A1 - Mangino, Massimo
A1 - Spector, Timothy D
A1 - Rienstra, Michiel
A1 - van de Vegte, Yordi J
A1 - van der Harst, Pim
A1 - Verweij, Niek
A1 - Kääb, Stefan
A1 - Schramm, Katharina
A1 - Sinner, Moritz F
A1 - Strauch, Konstantin
A1 - Cutler, Michael J
A1 - Fatkin, Diane
A1 - London, Barry
A1 - Olesen, Morten
A1 - Roden, Dan M
A1 - Benjamin Shoemaker, M
A1 - Gustav Smith, J
A1 - Biggs, Mary L
A1 - Bis, Joshua C
A1 - Brody, Jennifer A
A1 - Psaty, Bruce M
A1 - Rice, Kenneth
A1 - Sotoodehnia, Nona
A1 - De Grandi, Alessandro
A1 - Fuchsberger, Christian
A1 - Pattaro, Cristian
A1 - Pramstaller, Peter P
A1 - Ford, Ian
A1 - Wouter Jukema, J
A1 - Macfarlane, Peter W
A1 - Trompet, Stella
A1 - Dörr, Marcus
A1 - Felix, Stephan B
A1 - Völker, Uwe
A1 - Weiss, Stefan
A1 - Havulinna, Aki S
A1 - Jula, Antti
A1 - Sääksjärvi, Katri
A1 - Salomaa, Veikko
A1 - Guo, Xiuqing
A1 - Heckbert, Susan R
A1 - Lin, Henry J
A1 - Rotter, Jerome I
A1 - Taylor, Kent D
A1 - Yao, Jie
A1 - de Mutsert, Renée
A1 - Maan, Arie C
A1 - Mook-Kanamori, Dennis O
A1 - Noordam, Raymond
A1 - Cucca, Francesco
A1 - Ding, Jun
A1 - Lakatta, Edward G
A1 - Qian, Yong
A1 - Tarasov, Kirill V
A1 - Levy, Daniel
A1 - Lin, Honghuang
A1 - Newton-Cheh, Christopher H
A1 - Lunetta, Kathryn L
A1 - Murray, Alison D
A1 - Porteous, David J
A1 - Smith, Blair H
A1 - Stricker, Bruno H
A1 - Uitterlinden, Andre
A1 - van den Berg, Marten E
A1 - Haessler, Jeffrey
A1 - Jackson, Rebecca D
A1 - Kooperberg, Charles
A1 - Peters, Ulrike
A1 - Reiner, Alexander P
A1 - Whitsel, Eric A
A1 - Alonso, Alvaro
A1 - Arking, Dan E
A1 - Boerwinkle, Eric
A1 - Ehret, Georg B
A1 - Soliman, Elsayed Z
A1 - Avery, Christy L
A1 - Gogarten, Stephanie M
A1 - Kerr, Kathleen F
A1 - Laurie, Cathy C
A1 - Seyerle, Amanda A
A1 - Stilp, Adrienne
A1 - Assa, Solmaz
A1 - Abdullah Said, M
A1 - Yldau van der Ende, M
A1 - Lambiase, Pier D
A1 - Orini, Michele
A1 - Ramirez, Julia
A1 - Van Duijvenboden, Stefan
A1 - Arnar, David O
A1 - Gudbjartsson, Daniel F
A1 - Holm, Hilma
A1 - Sulem, Patrick
A1 - Thorleifsson, Gudmar
A1 - Thorolfsdottir, Rosa B
A1 - Thorsteinsdottir, Unnur
A1 - Benjamin, Emelia J
A1 - Tinker, Andrew
A1 - Stefansson, Kari
A1 - Ellinor, Patrick T
A1 - Jamshidi, Yalda
A1 - Lubitz, Steven A
A1 - Munroe, Patricia B
AB - The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.
VL - 11
IS - 1
ER -
TY - JOUR
T1 - Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals.
JF - Commun Biol
Y1 - 2022
A1 - Winkler, Thomas W
A1 - Rasheed, Humaira
A1 - Teumer, Alexander
A1 - Gorski, Mathias
A1 - Rowan, Bryce X
A1 - Stanzick, Kira J
A1 - Thomas, Laurent F
A1 - Tin, Adrienne
A1 - Hoppmann, Anselm
A1 - Chu, Audrey Y
A1 - Tayo, Bamidele
A1 - Thio, Chris H L
A1 - Cusi, Daniele
A1 - Chai, Jin-Fang
A1 - Sieber, Karsten B
A1 - Horn, Katrin
A1 - Li, Man
A1 - Scholz, Markus
A1 - Cocca, Massimiliano
A1 - Wuttke, Matthias
A1 - van der Most, Peter J
A1 - Yang, Qiong
A1 - Ghasemi, Sahar
A1 - Nutile, Teresa
A1 - Li, Yong
A1 - Pontali, Giulia
A1 - Günther, Felix
A1 - Dehghan, Abbas
A1 - Correa, Adolfo
A1 - Parsa, Afshin
A1 - Feresin, Agnese
A1 - de Vries, Aiko P J
A1 - Zonderman, Alan B
A1 - Smith, Albert V
A1 - Oldehinkel, Albertine J
A1 - De Grandi, Alessandro
A1 - Rosenkranz, Alexander R
A1 - Franke, Andre
A1 - Teren, Andrej
A1 - Metspalu, Andres
A1 - Hicks, Andrew A
A1 - Morris, Andrew P
A1 - Tönjes, Anke
A1 - Morgan, Anna
A1 - Podgornaia, Anna I
A1 - Peters, Annette
A1 - Körner, Antje
A1 - Mahajan, Anubha
A1 - Campbell, Archie
A1 - Freedman, Barry I
A1 - Spedicati, Beatrice
A1 - Ponte, Belen
A1 - Schöttker, Ben
A1 - Brumpton, Ben
A1 - Banas, Bernhard
A1 - Krämer, Bernhard K
A1 - Jung, Bettina
A1 - Åsvold, Bjørn Olav
A1 - Smith, Blair H
A1 - Ning, Boting
A1 - Penninx, Brenda W J H
A1 - Vanderwerff, Brett R
A1 - Psaty, Bruce M
A1 - Kammerer, Candace M
A1 - Langefeld, Carl D
A1 - Hayward, Caroline
A1 - Spracklen, Cassandra N
A1 - Robinson-Cohen, Cassianne
A1 - Hartman, Catharina A
A1 - Lindgren, Cecilia M
A1 - Wang, Chaolong
A1 - Sabanayagam, Charumathi
A1 - Heng, Chew-Kiat
A1 - Lanzani, Chiara
A1 - Khor, Chiea-Chuen
A1 - Cheng, Ching-Yu
A1 - Fuchsberger, Christian
A1 - Gieger, Christian
A1 - Shaffer, Christian M
A1 - Schulz, Christina-Alexandra
A1 - Willer, Cristen J
A1 - Chasman, Daniel I
A1 - Gudbjartsson, Daniel F
A1 - Ruggiero, Daniela
A1 - Toniolo, Daniela
A1 - Czamara, Darina
A1 - Porteous, David J
A1 - Waterworth, Dawn M
A1 - Mascalzoni, Deborah
A1 - Mook-Kanamori, Dennis O
A1 - Reilly, Dermot F
A1 - Daw, E Warwick
A1 - Hofer, Edith
A1 - Boerwinkle, Eric
A1 - Salvi, Erika
A1 - Bottinger, Erwin P
A1 - Tai, E-Shyong
A1 - Catamo, Eulalia
A1 - Rizzi, Federica
A1 - Guo, Feng
A1 - Rivadeneira, Fernando
A1 - Guilianini, Franco
A1 - Sveinbjornsson, Gardar
A1 - Ehret, Georg
A1 - Waeber, Gérard
A1 - Biino, Ginevra
A1 - Girotto, Giorgia
A1 - Pistis, Giorgio
A1 - Nadkarni, Girish N
A1 - Delgado, Graciela E
A1 - Montgomery, Grant W
A1 - Snieder, Harold
A1 - Campbell, Harry
A1 - White, Harvey D
A1 - Gao, He
A1 - Stringham, Heather M
A1 - Schmidt, Helena
A1 - Li, Hengtong
A1 - Brenner, Hermann
A1 - Holm, Hilma
A1 - Kirsten, Holgen
A1 - Kramer, Holly
A1 - Rudan, Igor
A1 - Nolte, Ilja M
A1 - Tzoulaki, Ioanna
A1 - Olafsson, Isleifur
A1 - Martins, Jade
A1 - Cook, James P
A1 - Wilson, James F
A1 - Halbritter, Jan
A1 - Felix, Janine F
A1 - Divers, Jasmin
A1 - Kooner, Jaspal S
A1 - Lee, Jeannette Jen-Mai
A1 - O'Connell, Jeffrey
A1 - Rotter, Jerome I
A1 - Liu, Jianjun
A1 - Xu, Jie
A1 - Thiery, Joachim
A1 - Arnlöv, Johan
A1 - Kuusisto, Johanna
A1 - Jakobsdottir, Johanna
A1 - Tremblay, Johanne
A1 - Chambers, John C
A1 - Whitfield, John B
A1 - Gaziano, John M
A1 - Marten, Jonathan
A1 - Coresh, Josef
A1 - Jonas, Jost B
A1 - Mychaleckyj, Josyf C
A1 - Christensen, Kaare
A1 - Eckardt, Kai-Uwe
A1 - Mohlke, Karen L
A1 - Endlich, Karlhans
A1 - Dittrich, Katalin
A1 - Ryan, Kathleen A
A1 - Rice, Kenneth M
A1 - Taylor, Kent D
A1 - Ho, Kevin
A1 - Nikus, Kjell
A1 - Matsuda, Koichi
A1 - Strauch, Konstantin
A1 - Miliku, Kozeta
A1 - Hveem, Kristian
A1 - Lind, Lars
A1 - Wallentin, Lars
A1 - Yerges-Armstrong, Laura M
A1 - Raffield, Laura M
A1 - Phillips, Lawrence S
A1 - Launer, Lenore J
A1 - Lyytikäinen, Leo-Pekka
A1 - Lange, Leslie A
A1 - Citterio, Lorena
A1 - Klaric, Lucija
A1 - Ikram, M Arfan
A1 - Ising, Marcus
A1 - Kleber, Marcus E
A1 - Francescatto, Margherita
A1 - Concas, Maria Pina
A1 - Ciullo, Marina
A1 - Piratsu, Mario
A1 - Orho-Melander, Marju
A1 - Laakso, Markku
A1 - Loeffler, Markus
A1 - Perola, Markus
A1 - de Borst, Martin H
A1 - Gögele, Martin
A1 - Bianca, Martina La
A1 - Lukas, Mary Ann
A1 - Feitosa, Mary F
A1 - Biggs, Mary L
A1 - Wojczynski, Mary K
A1 - Kavousi, Maryam
A1 - Kanai, Masahiro
A1 - Akiyama, Masato
A1 - Yasuda, Masayuki
A1 - Nauck, Matthias
A1 - Waldenberger, Melanie
A1 - Chee, Miao-Li
A1 - Chee, Miao-Ling
A1 - Boehnke, Michael
A1 - Preuss, Michael H
A1 - Stumvoll, Michael
A1 - Province, Michael A
A1 - Evans, Michele K
A1 - O'Donoghue, Michelle L
A1 - Kubo, Michiaki
A1 - Kähönen, Mika
A1 - Kastarinen, Mika
A1 - Nalls, Mike A
A1 - Kuokkanen, Mikko
A1 - Ghanbari, Mohsen
A1 - Bochud, Murielle
A1 - Josyula, Navya Shilpa
A1 - Martin, Nicholas G
A1 - Tan, Nicholas Y Q
A1 - Palmer, Nicholette D
A1 - Pirastu, Nicola
A1 - Schupf, Nicole
A1 - Verweij, Niek
A1 - Hutri-Kähönen, Nina
A1 - Mononen, Nina
A1 - Bansal, Nisha
A1 - Devuyst, Olivier
A1 - Melander, Olle
A1 - Raitakari, Olli T
A1 - Polasek, Ozren
A1 - Manunta, Paolo
A1 - Gasparini, Paolo
A1 - Mishra, Pashupati P
A1 - Sulem, Patrick
A1 - Magnusson, Patrik K E
A1 - Elliott, Paul
A1 - Ridker, Paul M
A1 - Hamet, Pavel
A1 - Svensson, Per O
A1 - Joshi, Peter K
A1 - Kovacs, Peter
A1 - Pramstaller, Peter P
A1 - Rossing, Peter
A1 - Vollenweider, Peter
A1 - van der Harst, Pim
A1 - Dorajoo, Rajkumar
A1 - Sim, Ralene Z H
A1 - Burkhardt, Ralph
A1 - Tao, Ran
A1 - Noordam, Raymond
A1 - Mägi, Reedik
A1 - Schmidt, Reinhold
A1 - de Mutsert, Renée
A1 - Rueedi, Rico
A1 - van Dam, Rob M
A1 - Carroll, Robert J
A1 - Gansevoort, Ron T
A1 - Loos, Ruth J F
A1 - Felicita, Sala Cinzia
A1 - Sedaghat, Sanaz
A1 - Padmanabhan, Sandosh
A1 - Freitag-Wolf, Sandra
A1 - Pendergrass, Sarah A
A1 - Graham, Sarah E
A1 - Gordon, Scott D
A1 - Hwang, Shih-Jen
A1 - Kerr, Shona M
A1 - Vaccargiu, Simona
A1 - Patil, Snehal B
A1 - Hallan, Stein
A1 - Bakker, Stephan J L
A1 - Lim, Su-Chi
A1 - Lucae, Susanne
A1 - Vogelezang, Suzanne
A1 - Bergmann, Sven
A1 - Corre, Tanguy
A1 - Ahluwalia, Tarunveer S
A1 - Lehtimäki, Terho
A1 - Boutin, Thibaud S
A1 - Meitinger, Thomas
A1 - Wong, Tien-Yin
A1 - Bergler, Tobias
A1 - Rabelink, Ton J
A1 - Esko, Tõnu
A1 - Haller, Toomas
A1 - Thorsteinsdottir, Unnur
A1 - Völker, Uwe
A1 - Foo, Valencia Hui Xian
A1 - Salomaa, Veikko
A1 - Vitart, Veronique
A1 - Giedraitis, Vilmantas
A1 - Gudnason, Vilmundur
A1 - Jaddoe, Vincent W V
A1 - Huang, Wei
A1 - Zhang, Weihua
A1 - Wei, Wen Bin
A1 - Kiess, Wieland
A1 - März, Winfried
A1 - Koenig, Wolfgang
A1 - Lieb, Wolfgang
A1 - Gào, Xīn
A1 - Sim, Xueling
A1 - Wang, Ya Xing
A1 - Friedlander, Yechiel
A1 - Tham, Yih-Chung
A1 - Kamatani, Yoichiro
A1 - Okada, Yukinori
A1 - Milaneschi, Yuri
A1 - Yu, Zhi
A1 - Stark, Klaus J
A1 - Stefansson, Kari
A1 - Böger, Carsten A
A1 - Hung, Adriana M
A1 - Kronenberg, Florian
A1 - Köttgen, Anna
A1 - Pattaro, Cristian
A1 - Heid, Iris M
KW - Creatinine
KW - Diabetes Mellitus
KW - Diabetic Nephropathies
KW - Genome-Wide Association Study
KW - Glomerular Filtration Rate
KW - Humans
KW - Kidney
AB - Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (n = 178,691, n = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
VL - 5
IS - 1
ER -
TY - JOUR
T1 - Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies.
JF - Kidney Int
Y1 - 2022
A1 - Gorski, Mathias
A1 - Rasheed, Humaira
A1 - Teumer, Alexander
A1 - Thomas, Laurent F
A1 - Graham, Sarah E
A1 - Sveinbjornsson, Gardar
A1 - Winkler, Thomas W
A1 - Günther, Felix
A1 - Stark, Klaus J
A1 - Chai, Jin-Fang
A1 - Tayo, Bamidele O
A1 - Wuttke, Matthias
A1 - Li, Yong
A1 - Tin, Adrienne
A1 - Ahluwalia, Tarunveer S
A1 - Arnlöv, Johan
A1 - Åsvold, Bjørn Olav
A1 - Bakker, Stephan J L
A1 - Banas, Bernhard
A1 - Bansal, Nisha
A1 - Biggs, Mary L
A1 - Biino, Ginevra
A1 - Böhnke, Michael
A1 - Boerwinkle, Eric
A1 - Bottinger, Erwin P
A1 - Brenner, Hermann
A1 - Brumpton, Ben
A1 - Carroll, Robert J
A1 - Chaker, Layal
A1 - Chalmers, John
A1 - Chee, Miao-Li
A1 - Chee, Miao-Ling
A1 - Cheng, Ching-Yu
A1 - Chu, Audrey Y
A1 - Ciullo, Marina
A1 - Cocca, Massimiliano
A1 - Cook, James P
A1 - Coresh, Josef
A1 - Cusi, Daniele
A1 - de Borst, Martin H
A1 - Degenhardt, Frauke
A1 - Eckardt, Kai-Uwe
A1 - Endlich, Karlhans
A1 - Evans, Michele K
A1 - Feitosa, Mary F
A1 - Franke, Andre
A1 - Freitag-Wolf, Sandra
A1 - Fuchsberger, Christian
A1 - Gampawar, Piyush
A1 - Gansevoort, Ron T
A1 - Ghanbari, Mohsen
A1 - Ghasemi, Sahar
A1 - Giedraitis, Vilmantas
A1 - Gieger, Christian
A1 - Gudbjartsson, Daniel F
A1 - Hallan, Stein
A1 - Hamet, Pavel
A1 - Hishida, Asahi
A1 - Ho, Kevin
A1 - Hofer, Edith
A1 - Holleczek, Bernd
A1 - Holm, Hilma
A1 - Hoppmann, Anselm
A1 - Horn, Katrin
A1 - Hutri-Kähönen, Nina
A1 - Hveem, Kristian
A1 - Hwang, Shih-Jen
A1 - Ikram, M Arfan
A1 - Josyula, Navya Shilpa
A1 - Jung, Bettina
A1 - Kähönen, Mika
A1 - Karabegović, Irma
A1 - Khor, Chiea-Chuen
A1 - Koenig, Wolfgang
A1 - Kramer, Holly
A1 - Krämer, Bernhard K
A1 - Kuhnel, Brigitte
A1 - Kuusisto, Johanna
A1 - Laakso, Markku
A1 - Lange, Leslie A
A1 - Lehtimäki, Terho
A1 - Li, Man
A1 - Lieb, Wolfgang
A1 - Lind, Lars
A1 - Lindgren, Cecilia M
A1 - Loos, Ruth J F
A1 - Lukas, Mary Ann
A1 - Lyytikäinen, Leo-Pekka
A1 - Mahajan, Anubha
A1 - Matias-Garcia, Pamela R
A1 - Meisinger, Christa
A1 - Meitinger, Thomas
A1 - Melander, Olle
A1 - Milaneschi, Yuri
A1 - Mishra, Pashupati P
A1 - Mononen, Nina
A1 - Morris, Andrew P
A1 - Mychaleckyj, Josyf C
A1 - Nadkarni, Girish N
A1 - Naito, Mariko
A1 - Nakatochi, Masahiro
A1 - Nalls, Mike A
A1 - Nauck, Matthias
A1 - Nikus, Kjell
A1 - Ning, Boting
A1 - Nolte, Ilja M
A1 - Nutile, Teresa
A1 - O'Donoghue, Michelle L
A1 - O'Connell, Jeffrey
A1 - Olafsson, Isleifur
A1 - Orho-Melander, Marju
A1 - Parsa, Afshin
A1 - Pendergrass, Sarah A
A1 - Penninx, Brenda W J H
A1 - Pirastu, Mario
A1 - Preuss, Michael H
A1 - Psaty, Bruce M
A1 - Raffield, Laura M
A1 - Raitakari, Olli T
A1 - Rheinberger, Myriam
A1 - Rice, Kenneth M
A1 - Rizzi, Federica
A1 - Rosenkranz, Alexander R
A1 - Rossing, Peter
A1 - Rotter, Jerome I
A1 - Ruggiero, Daniela
A1 - Ryan, Kathleen A
A1 - Sabanayagam, Charumathi
A1 - Salvi, Erika
A1 - Schmidt, Helena
A1 - Schmidt, Reinhold
A1 - Scholz, Markus
A1 - Schöttker, Ben
A1 - Schulz, Christina-Alexandra
A1 - Sedaghat, Sanaz
A1 - Shaffer, Christian M
A1 - Sieber, Karsten B
A1 - Sim, Xueling
A1 - Sims, Mario
A1 - Snieder, Harold
A1 - Stanzick, Kira J
A1 - Thorsteinsdottir, Unnur
A1 - Stocker, Hannah
A1 - Strauch, Konstantin
A1 - Stringham, Heather M
A1 - Sulem, Patrick
A1 - Szymczak, Silke
A1 - Taylor, Kent D
A1 - Thio, Chris H L
A1 - Tremblay, Johanne
A1 - Vaccargiu, Simona
A1 - van der Harst, Pim
A1 - van der Most, Peter J
A1 - Verweij, Niek
A1 - Völker, Uwe
A1 - Wakai, Kenji
A1 - Waldenberger, Melanie
A1 - Wallentin, Lars
A1 - Wallner, Stefan
A1 - Wang, Judy
A1 - Waterworth, Dawn M
A1 - White, Harvey D
A1 - Willer, Cristen J
A1 - Wong, Tien-Yin
A1 - Woodward, Mark
A1 - Yang, Qiong
A1 - Yerges-Armstrong, Laura M
A1 - Zimmermann, Martina
A1 - Zonderman, Alan B
A1 - Bergler, Tobias
A1 - Stefansson, Kari
A1 - Böger, Carsten A
A1 - Pattaro, Cristian
A1 - Köttgen, Anna
A1 - Kronenberg, Florian
A1 - Heid, Iris M
AB - Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
ER -
TY - JOUR
T1 - X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements.
JF - Nat Commun
Y1 - 2024
A1 - Scholz, Markus
A1 - Horn, Katrin
A1 - Pott, Janne
A1 - Wuttke, Matthias
A1 - Kühnapfel, Andreas
A1 - Nasr, M Kamal
A1 - Kirsten, Holger
A1 - Li, Yong
A1 - Hoppmann, Anselm
A1 - Gorski, Mathias
A1 - Ghasemi, Sahar
A1 - Li, Man
A1 - Tin, Adrienne
A1 - Chai, Jin-Fang
A1 - Cocca, Massimiliano
A1 - Wang, Judy
A1 - Nutile, Teresa
A1 - Akiyama, Masato
A1 - Åsvold, Bjørn Olav
A1 - Bansal, Nisha
A1 - Biggs, Mary L
A1 - Boutin, Thibaud
A1 - Brenner, Hermann
A1 - Brumpton, Ben
A1 - Burkhardt, Ralph
A1 - Cai, Jianwen
A1 - Campbell, Archie
A1 - Campbell, Harry
A1 - Chalmers, John
A1 - Chasman, Daniel I
A1 - Chee, Miao Ling
A1 - Chee, Miao Li
A1 - Chen, Xu
A1 - Cheng, Ching-Yu
A1 - Cifkova, Renata
A1 - Daviglus, Martha
A1 - Delgado, Graciela
A1 - Dittrich, Katalin
A1 - Edwards, Todd L
A1 - Endlich, Karlhans
A1 - Michael Gaziano, J
A1 - Giri, Ayush
A1 - Giulianini, Franco
A1 - Gordon, Scott D
A1 - Gudbjartsson, Daniel F
A1 - Hallan, Stein
A1 - Hamet, Pavel
A1 - Hartman, Catharina A
A1 - Hayward, Caroline
A1 - Heid, Iris M
A1 - Hellwege, Jacklyn N
A1 - Holleczek, Bernd
A1 - Holm, Hilma
A1 - Hutri-Kähönen, Nina
A1 - Hveem, Kristian
A1 - Isermann, Berend
A1 - Jonas, Jost B
A1 - Joshi, Peter K
A1 - Kamatani, Yoichiro
A1 - Kanai, Masahiro
A1 - Kastarinen, Mika
A1 - Khor, Chiea Chuen
A1 - Kiess, Wieland
A1 - Kleber, Marcus E
A1 - Körner, Antje
A1 - Kovacs, Peter
A1 - Krajcoviechova, Alena
A1 - Kramer, Holly
A1 - Krämer, Bernhard K
A1 - Kuokkanen, Mikko
A1 - Kähönen, Mika
A1 - Lange, Leslie A
A1 - Lash, James P
A1 - Lehtimäki, Terho
A1 - Li, Hengtong
A1 - Lin, Bridget M
A1 - Liu, Jianjun
A1 - Loeffler, Markus
A1 - Lyytikäinen, Leo-Pekka
A1 - Magnusson, Patrik K E
A1 - Martin, Nicholas G
A1 - Matsuda, Koichi
A1 - Milaneschi, Yuri
A1 - Mishra, Pashupati P
A1 - Mononen, Nina
A1 - Montgomery, Grant W
A1 - Mook-Kanamori, Dennis O
A1 - Mychaleckyj, Josyf C
A1 - März, Winfried
A1 - Nauck, Matthias
A1 - Nikus, Kjell
A1 - Nolte, Ilja M
A1 - Noordam, Raymond
A1 - Okada, Yukinori
A1 - Olafsson, Isleifur
A1 - Oldehinkel, Albertine J
A1 - Penninx, Brenda W J H
A1 - Perola, Markus
A1 - Pirastu, Nicola
A1 - Polasek, Ozren
A1 - Porteous, David J
A1 - Poulain, Tanja
A1 - Psaty, Bruce M
A1 - Rabelink, Ton J
A1 - Raffield, Laura M
A1 - Raitakari, Olli T
A1 - Rasheed, Humaira
A1 - Reilly, Dermot F
A1 - Rice, Kenneth M
A1 - Richmond, Anne
A1 - Ridker, Paul M
A1 - Rotter, Jerome I
A1 - Rudan, Igor
A1 - Sabanayagam, Charumathi
A1 - Salomaa, Veikko
A1 - Schneiderman, Neil
A1 - Schöttker, Ben
A1 - Sims, Mario
A1 - Snieder, Harold
A1 - Stark, Klaus J
A1 - Stefansson, Kari
A1 - Stocker, Hannah
A1 - Stumvoll, Michael
A1 - Sulem, Patrick
A1 - Sveinbjornsson, Gardar
A1 - Svensson, Per O
A1 - Tai, E-Shyong
A1 - Taylor, Kent D
A1 - Tayo, Bamidele O
A1 - Teren, Andrej
A1 - Tham, Yih-Chung
A1 - Thiery, Joachim
A1 - Thio, Chris H L
A1 - Thomas, Laurent F
A1 - Tremblay, Johanne
A1 - Tönjes, Anke
A1 - van der Most, Peter J
A1 - Vitart, Veronique
A1 - Völker, Uwe
A1 - Wang, Ya Xing
A1 - Wang, Chaolong
A1 - Wei, Wen Bin
A1 - Whitfield, John B
A1 - Wild, Sarah H
A1 - Wilson, James F
A1 - Winkler, Thomas W
A1 - Wong, Tien-Yin
A1 - Woodward, Mark
A1 - Sim, Xueling
A1 - Chu, Audrey Y
A1 - Feitosa, Mary F
A1 - Thorsteinsdottir, Unnur
A1 - Hung, Adriana M
A1 - Teumer, Alexander
A1 - Franceschini, Nora
A1 - Parsa, Afshin
A1 - Köttgen, Anna
A1 - Schlosser, Pascal
A1 - Pattaro, Cristian
KW - Androgens
KW - Chromosomes, Human, X
KW - Female
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Humans
KW - Kidney
KW - Male
KW - Polymorphism, Single Nucleotide
KW - Response Elements
KW - Tetraspanins
AB - X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.
VL - 15
IS - 1
ER -