Genetic loci influencing kidney function and chronic kidney disease
John C. Chambers,Weihua Zhang,Graham M. Lord,Graham M. Lord,Pim van der Harst,Debbie A Lawlor,Joban Sehmi,Daniel P. Gale,Mark N. Wass,Kourosh R. Ahmadi,Stephan J. L. Bakker,Jacqui Beckmann,Henk J. G. Bilo,Murielle Bochud,Morris J. Brown,Mark J. Caulfield,John M. C. Connell,H. Terence Cook,Ioana Cotlarciuc,George Davey Smith,Ranil de Silva,Guohong Deng,Olivier Devuyst,Lambert D Dikkeschei,Nada Dimkovic,Mark Dockrell,Anna F. Dominiczak,Shah Ebrahim,Thomas Eggermann,Martin Farrall,Luigi Ferrucci,Jürgen Floege,Nita G. Forouhi,Ron T. Gansevoort,Xijin Han,Bo Hedblad,Jaap J. Homan van der Heide,Bouke G. Hepkema,Maria P. Hernandez-Fuentes,Maria P. Hernandez-Fuentes,Elina Hyppönen,Toby Johnson,Paul E. de Jong,Nanne Kleefstra,Vasiliki Lagou,Marta Lapsley,Yun Li,Ruth J. F. Loos,Jian'an Luan,Karin Luttropp,Céline Maréchal,Olle Melander,Patricia B. Munroe,Louise Nordfors,Afshin Parsa,Leena Peltonen,Leena Peltonen,Leena Peltonen,Brenda W.J.H. Penninx,Brenda W.J.H. Penninx,Brenda W.J.H. Penninx,Esperanza Perucha,Esperanza Perucha,Anneli Pouta,Inga Prokopenko,Paul Roderick,Aimo Ruokonen,Nilesh J. Samani,Serena Sanna,Martin Schalling,David Schlessinger,Georg Schlieper,Marc A. Seelen,Alan R. Shuldiner,Marketa Sjögren,Johannes H. Smit,Johannes H. Smit,Johannes H. Smit,Harold Snieder,Nicole Soranzo,Tim D. Spector,Peter Stenvinkel,Michael J.E. Sternberg,R. Swaminathan,Toshiko Tanaka,L.J. Ubink-Veltmaat,Manuela Uda,Peter Vollenweider,Chris Wallace,Dawn M. Waterworth,Klaus Zerres,Gérard Waeber,Nicholas J. Wareham,Patrick H. Maxwell,Mark I. McCarthy,Marjo-Riitta Järvelin,Vincent Mooser,Gonçalo R. Abecasis,Liz Lightstone,James Scott,Gerjan Navis,Paul Elliott,Jaspal S. Kooner +102 more
TLDR
Using genome-wide association, common variants at 2p12–p13, 6q26, 17q23 and 19q13 associated with serum creatinine associated with chronic kidney disease are identified.Abstract:
Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.read more
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An integrated map of genetic variation from 1,092 human genomes
Gonçalo R. Abecasis,Adam Auton,Lisa D. Brooks,Mark A. DePristo,Richard Durbin,Robert E. Handsaker,Robert E. Handsaker,Hyun Min Kang,Gabor T. Marth,Gil McVean +9 more
TL;DR: It is shown that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites.
Journal ArticleDOI
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk
Georg Ehret,Georg Ehret,Georg Ehret,Patricia B. Munroe,Kenneth Rice,Murielle Bochud,Andrew D. Johnson,Daniel I. Chasman,Albert V. Smith,Martin D. Tobin,Germaine C. Verwoert,Shih-Jen Hwang,Vasyl Pihur,Peter Vollenweider,Paul F. O'Reilly,Najaf Amin,Jennifer L. Bragg-Gresham,Alexander Teumer,Nicole L. Glazer,Lenore J. Launer,Jing Hua Zhao,Yurii S. Aulchenko,Simon Heath,Siim Sõber,Afshin Parsa,Jian'an Luan,Pankaj Arora,Abbas Dehghan,Feng Zhang,Gavin Lucas,Andrew A. Hicks,Anne U. Jackson,John F. Peden,Toshiko Tanaka,Sarah H. Wild,Igor Rudan,Igor Rudan,Wilmar Igl,Yuri Milaneschi,Alex Parker,Cristiano Fava,Cristiano Fava,John C. Chambers,John C. Chambers,Ervin R. Fox,Meena Kumari,Min Jin Go,Pim van der Harst,Wen Hong Linda Kao,Marketa Sjögren,D. G. Vinay,Myriam Alexander,Yasuharu Tabara,Sue Shaw-Hawkins,Peter H. Whincup,Yongmei Liu,Gang Shi,Johanna Kuusisto,Bamidele O. Tayo,Mark Seielstad,Mark Seielstad,Xueling Sim,Khanh-Dung H. Nguyen,Terho Lehtimäki,Giuseppe Matullo,Ying Wu,Tom R. Gaunt,N. Charlotte Onland-Moret,Mark E. Cooper,Carl G. P. Platou,Elin Org,Rebecca Hardy,Santosh Dahgam,Jutta Palmen,Veronique Vitart,Peter S. Braund,Peter S. Braund,Tatiana Kuznetsova,Cuno S.P.M. Uiterwaal,Adebowale Adeyemo,Walter Palmas,Harry Campbell,Barbara Ludwig,Maciej Tomaszewski,Maciej Tomaszewski,Ioanna Tzoulaki,Ioanna Tzoulaki,Nicholette D. Palmer,Thor Aspelund,Melissa Garcia,Yen Pei C. Chang,Jeffrey R. O'Connell,Nanette I. Steinle,Diederick E. Grobbee,Dan E. Arking,Sharon L.R. Kardia,Alanna C. Morrison,Dena G. Hernandez,Samer S. Najjar,Samer S. Najjar,Wendy L. McArdle,David Hadley,David Hadley,Morris J. Brown,John M. C. Connell,Aroon D. Hingorani,Ian N. M. Day,Debbie A Lawlor,John Beilby,Robert W. Lawrence,Robert Clarke,Jemma C. Hopewell,Halit Ongen,Albert W. Dreisbach,Yali Li,J. Hunter Young,Joshua C. Bis,Mika Kähönen,Jorma Viikari,Linda S. Adair,Nanette R. Lee,Ming-Huei Chen,Matthias Olden,Cristian Pattaro,Judith A. Hoffman Bolton,Anna Köttgen,Anna Köttgen,Sven Bergmann,Sven Bergmann,Vincent Mooser,Nish Chaturvedi,Timothy M. Frayling,Muhammad Islam,Tazeen H. Jafar,Jeanette Erdmann,Smita R. Kulkarni,Stefan R. Bornstein,Jürgen Grässler,Leif Groop,Benjamin F. Voight,Johannes Kettunen,Philip Howard,Andrew M. Taylor,Simonetta Guarrera,Fulvio Ricceri,Valur Emilsson,Andrew S. Plump,Inês Barroso,Inês Barroso,Kay-Tee Khaw,Alan B. Weder,Steven C. Hunt,Yan V. Sun,Richard N. Bergman,Francis S. Collins,Lori L. Bonnycastle,Laura J. Scott,Heather M. Stringham,Leena Peltonen,Markus Perola,Erkki Vartiainen,Stefan Martin Brand,Jan A. Staessen,Thomas J. Wang,Thomas J. Wang,Paul Burton,Paul Burton,María Soler Artigas,Yanbin Dong,Harold Snieder,Harold Snieder,Xiaoling Wang,Haidong Zhu,Kurt Lohman,Megan E. Rudock,Susan R. Heckbert,Susan R. Heckbert,Nicholas L. Smith,Nicholas L. Smith,Nicholas L. Smith,Kerri L. Wiggins,Ayo P. 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Humphries,John Danesh,Asif Rasheed,Anuj Goel,Anders Hamsten,Hugh Watkins,Stephan J. L. Bakker,Wiek H. van Gilst,C. S. Janipalli,K. Radha Mani,Chittaranjan S. Yajnik,Albert Hofman,Francesco U.S. Mattace-Raso,Ben A. Oostra,Ayse Demirkan,Aaron Isaacs,Fernando Rivadeneira,Edward G. Lakatta,Marco Orrù,Angelo Scuteri,Mika Ala-Korpela,Mika Ala-Korpela,Antti J. Kangas,Leo-Pekka Lyytikäinen,Pasi Soininen,Pasi Soininen,Taru Tukiainen,Taru Tukiainen,Taru Tukiainen,Peter Würtz,Peter Würtz,Peter Würtz,Rick Twee-HeeOng,Rick Twee-HeeOng,Marcus Dörr,Heyo K. Kroemer,Uwe Völker,Henry Völzke,Pilar Galan,Serge Hercberg,Mark Lathrop,Diana Zelenika,Panos Deloukas,Massimo Mangino,Tim D. Spector,Guangju Zhai,James F. Meschia,Mike A. Nalls,Pankaj Sharma,Janoš Terzić,M.V. Kranthi Kumar,Matthew Denniff,Ewa Zukowska-Szczechowska,Lynne E. Wagenknecht,F. Gerald R. Fowkes,Fadi J. Charchar,Peter Schwarz,Caroline Hayward,Xiuqing Guo,Charles N. Rotimi,Michiel L. Bots,Eva Brand,Nilesh J. Samani,Nilesh J. 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Rotter,Rainer Rettig,Manuela Uda,David P. Strachan,Jacqueline C. M. Witteman,Anna-Liisa Hartikainen,Jacques S. Beckmann,Eric Boerwinkle,Ramachandran S. Vasan,Ramachandran S. Vasan,Michael Boehnke,Martin G. Larson,Martin G. Larson,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Bruce M. Psaty,Bruce M. Psaty,Gonçalo R. Abecasis,Aravinda Chakravarti,Paul Elliott,Cornelia M. van Duijn,Christopher Newton-Cheh,Christopher Newton-Cheh,Daniel Levy,Mark J. Caulfield,Toby Johnson +391 more
TL;DR: A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function, and these findings suggest potential novel therapeutic pathways for cardiovascular disease prevention.
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Human metabolic individuality in biomedical and pharmaceutical research
Karsten Suhre,So-Youn Shin,Ann-Kristin Petersen,Robert P. Mohney,David Meredith,Brigitte Wägele,Elisabeth Altmaier,Panos Deloukas,Jeanette Erdmann,Elin Grundberg,Elin Grundberg,Christopher J Hammond,Martin Hrabé de Angelis,Gabi Kastenmüller,Anna Köttgen,Florian Kronenberg,Massimo Mangino,Christa Meisinger,Thomas Meitinger,Hans-Werner Mewes,Michael V. Milburn,Cornelia Prehn,Johannes Raffler,Janina S. Ried,Werner Römisch-Margl,Nilesh J. Samani,Kerrin S. Small,H.-Erich Wichmann,Guangju Zhai,Thomas Illig,Tim D. Spector,Jerzy Adamski,Nicole Soranzo,Christian Gieger +33 more
TL;DR: A comprehensive analysis of genotype-dependent metabolic phenotypes using a genome-wide association study with non-targeted metabolomics to identify genetic loci associated with blood metabolite concentrations and generates many new hypotheses for biomedical and pharmaceutical research.
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Evolving importance of kidney disease: from subspecialty to global health burden
Kai-Uwe Eckardt,Josef Coresh,Olivier Devuyst,Richard J. Johnson,Anna Köttgen,Andrew S. Levey,Adeera Levin +6 more
TL;DR: Strong, graded, and consistent associations exist between clinical prognosis and two hallmarks of chronic kidney disease: reduced glomerular filtration rate and increased urinary albumin excretion.
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Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.
TL;DR: In this paper, the authors carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations.
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