8 research outputs found
Meta-analysis of type 2 Diabetes in African Americans Consortium
- Author
- Abboud H.
- Abecasis G.R.
- Adeyemo A.
- Adler S.
- Ahmadi K.R.
- Ainali C.
- Altshuler D.
- Amin N.
- An P.
- Arar N.
- Ardlie K.
- Armstrong L.L.
- Aulchenko Y.S.
- Avila P.C.
- Balkau B.
- Barrett A.
- Barroso I.
- Basford M.
- Bataille V.
- Bayton P.
- Becker D.M.
- Bell J.T.
- Benediktsson R.
- Bengtsson Boström K.
- Bennett A.J.
- Berg R.
- Bergman R.N.
- Bielak L.F.
- Bielinski S.
- Bielinski S.J.
- Blagieva R.
- Blot W.J.
- Bobelu A.
- Boehm B.O.
- Boehnke M.
- Boerwinkle E.
- Boerwinkle E.
- Bonnycastle L.L.
- Borecki I.B.
- Bottinger E.P.
- Bowden D.W.
- Bowden D.W.
- Bravenboer B.
- Briggs J.P.
- Brooks G.
- Brown Trinidad S.
- Budgett M.
- Buil A.
- Bumpstead S.
- Burke W.
- Burtt N.P.
- Cai Q.
- Campbell H.
- Carlson C.
- Carrell D.
- Cauchi S.
- Chakraborty R.
- Charpentier G.
- Chen B.H.
- Chen G.
- Chen L.
- Chen W.-M.
- Chen Y.D.I.
- Chines P.S.
- Chisholm R.L.
- Choudary V.
- Churchill L.R.
- Chute C.
- Clayton E.
- Collins F.S.
- Collins-Schramm H.E.
- Comeau M.E.
- Coresh J.
- Cornelis M.
- Cornfield D.
- Correa A.
- Couper D.
- Couper D.J.
- Crane P.
- Crawford D.
- Crawford D.C.
- Crawford G.
- Cummings S.R.
- Daly M.J.
- Darbar D.
- de Andrade M.
- Deloukas P.
- Denny J.C.
- Dermitzakis E.T.
- di Meglio P.
- Dimas A.S.
- Dina C.
- Ding K.
- Doney A.S.F.
- Doumatey A.
- Duggirala R.
- Dunston G.M.
- Dupuis J.
- Durbin R.
- Edwards S.
- Elliott A.L.
- Elliott K.S.
- Elston R.C.
- Erdos M.R.
- Evans D.S.
- Evans M.K.
- Ferreira T.
- Fink N.
- Florez J.C.
- Fondran C.
- Fornage M.
- Fost N.
- Fox C.S.
- Franklin C.S.
- Frayling T.M.
- Freedman B.I.
- Freedman B.I.
- Froguel P.
- Ganser M.
- Garcia C.
- Geoffrey Hayes M.
- Getz-Fradley L.
- Gieger C.
- Glass D.
- Gloyn A.L.
- Goddard K.
- Gonzalez J.
- Goodarzi M.O.
- Gottesman O.
- Goyes C.
- Grallert H.
- Grarup N.
- Green T.
- Greenland P.
- Griffin S.
- Groop L.
- Groves C.J.
- Grundberg E.
- Grundberg E.
- Guiducci C.
- Guo X.
- Guo X.
- Gyllensten U.
- Hadjadj S.
- Haines J.L.
- Hansen T.
- Hanson R.
- Hanson R.L.
- Hart G.
- Hart L.
- Hassanali N.
- Hassanali N.
- Hattersley A.T.
- Havens Ramirez A.
- Hayes M.G.
- Hedman Å.K.
- Henriksen J.
- Herder C.
- Hide W.A.
- Hitman G.A.
- Hofman A.
- Hofmann O.M.
- Horvath A.
- Hsueh W.-C.
- Hu F.B.
- Humbert L.
- Humowiecki J.
- Hunter D.J.
- Huth C.
- Hveem K.
- Ialacci S.
- Igo R.P.
- Illig T.
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- Ingram-Drake L.
- Ipp E.
- Isomaa B.
- Iyengar S.
- Iyengar S.K.
- Jackson A.U.
- Jarvik G.
- Jensen R.A.
- Johnson P.R.V.
- Jones L.
- Jr.
- Jr.
- Juan R.
- Jun G.
- Jørgensen T.
- Kabagambe E.K.
- Kao L.
- Kao W.H.L.
- Kao W.H.L.
- Kasinath B.S.
- Keene K.L.
- Kho A.N.
- Kibbe W.A.
- Kimmel P.L.
- Kitchner T.
- Klag M.
- Klopp N.
- Knowler W.C.
- Knowles D.
- Koenig B.
- Kong A.
- Kraft P.
- Kraja A.
- Kramp K.
- Krestyaninova M.
- Kullo I.
- Kuusisto J.
- Laakso M.
- Langefeld C.D.
- LaPage J.
- Larson E.B.
- Lauritzen T.
- Law M.
- Lemke A.A.
- Li J.
- Li M.
- Li1 H.
- Lieverse A.
- Lifton R.P.
- Lindgren C.M.
- Lindgren C.M.
- Linneman J.
- Liu J.
- Liu S.
- Liu Y.
- Long J.
- Long Y.
- Loos R.J.F.
- Lovelace R.
- Lowe C.E.
- Lowe W.L.
- Lowe W.L.
- Lu Y.
- Ludman E.
- Luethe C.
- Lyssenko V.
- Malia Fullerton S.
- Malin B.A.
- Marre M.
- Masys D.R.
- Mathias R.A.
- Mccarroll S.A.
- Mccarroll S.A.
- Mccarthy M.I.
- McCarthy M.I.
- McCarty C.A.
- Mcculloch L.J.
- McDavid A.
- McKnight B.
- Mead L.
- Meduri E.
- Meigs J.B.
- Meitinger T.
- Midthjell K.
- Miller A.
- Min J.L.
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- Montgomery S.B.
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- Morris A.D.
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- Mudgal P.
- Mychaleckyj J.C.
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- Narisu N.
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- Nayak U.
- Nelson R.G.
- Nestle F.O.
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- Nica A.C.
- Nilsson P.
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- Olson J.
- Owen K.R.
- O’Brien S.J.
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- Pacheco J.A.
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- Pahl M.
- Palbicki J.
- Palmer C.N.A.
- Palmer N.D.
- Pankow J.S.
- Pankow J.S.
- Parekh R.
- Parts L.
- Patel S.R.
- Pathak J.
- Payne F.
- Pedersen O.
- Peissig P.
- Perry J.R.B.
- Petersen A.-K.
- Peyser P.A.
- Phillips L.M.
- Pickens A.
- Plaetke R.
- Platou C.
- Potter S.
- Pramstaller P.P.
- Proença C.
- Prokopenko I.
- Province M.A.
- Psaty B.M.
- Pulley J.
- Qi L.
- Raffel L.J.
- Rasmussen L.
- Rasmussen-Torvik L.J.
- Rasooly R.
- Rathmann W.
- Raychaudhuri S.
- Rayner N.W.
- Reeser J.
- Rice K.
- Rich S.S.
- Rich S.S.
- Ritchie M.
- Ritchie M.D.
- Robertson N.R.
- Rocheleau G.
- Roden D.M.
- Roden M.
- Rotimi C.N.
- Rotter J.
- Rotter J.I.
- Rudan I.
- Saad M.F.
- Sale M.M.
- Sampson M.J.
- Sartorio V.
- Satko S.C.
- Savova G.
- Saxena R.
- Scavini M.
- Schelling J.
- Schildcrout J.S.
- Scott L.J.
- Sedor J.R.
- Sedor J.R.
- Segrè A.V.
- Sehgal A.
- Sekowska M.
- Seldin M.F.
- Sewemaenewa J.
- Shah V.
- Shields B.M.
- Shin S.-Y.
- Shrader P.
- Shriner D.
- Shu X.-O.
- Sigurdsson G.
- Sijbrands E.
- Sili I.
- Sims M.
- Singleton A.B.
- Siscovick D.S.
- Sladek R.
- Slaughter M.
- Small K.S.
- Smith M.E.
- Smith M.W.
- Snively B.M.
- Soranzo N.
- Spangler L.
- Sparsø T.
- Spector T.D.
- Spielman R.
- Starren J.
- Stefansson K.
- Stein L.D.
- Steinthorsdottir V.
- Stem M.
- Strassburger K.
- Stringham H.M.
- Sun Q.
- Sun Y.V.
- Surdulescu G.
- Swift A.J.
- Taylor H.A.
- Taylor K.
- The MAGIC investigators
- Thompson M.
- Thompson W.K.
- Thorand B.
- Thorleifsson G.
- Thorsteinsdottir U.
- Tichet J.
- Tsaprouni L.
- Tsoka S.
- Tuomi T.
- Tuomilehto J.
- Uitterlinden A.
- Vaidya D.
- van Dam R.M.
- van duijn C.M.
- van Haeften T.W.
- van Herpt T.
- van Hoek M.
- van Vliet-Ostaptchouk J.V.
- Viverette S.
- Voight B.F.
- Wagenknecht L.
- Walker B.
- Walker M.
- Walters G.B.
- Wareham N.J.
- Warnock D.
- Warren S.
- Waseta B.
- Watanabe R.M.
- Waudby C.
- Weedon M.N.
- Wei L.
- Welch R.P.
- Whitehead T.
- Wichmann H.-E.
- Wijmenga C.
- Wilk A.
- Wilke R.A.
- Willer C.J.
- Wilson J.F.
- Wilson J.G.
- Winkler C.
- Witteman J.
- Wolf W.A.
- Wu G.
- Wu J.
- Xu H.
- Yanek L.R.
- Yang L.
- Yang T.-P.
- Young R.
- Zager P.
- Zaletel E.
- Zeggini E.
- Zhao W.
- Zheng W.
- Zonderman A.B.
- Zondervan K.T.
- Publication venue
- Publication date
- 01/01/2014
- Field of study
Get PDFType 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR) = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe
The Pathology and Chemistry of a Case of Gargoylism
- Author
- Publication venue
- 'BMJ'
- Publication date
- Field of study
No full textAntigen recognition by T-cells and its suppression. Significance and origin of rosette-forming cells.
- Author
- ADA G.L.
- ANDERSSON B.
- ARGYRIS B.F.
- BACH C.
- BACH J.F.
- BACH J.F.
- BACH J.F.
- BACH M.A.
- BARTH R.F.
- BASTEN A.
- BERENBAUM M.C.
- BIozzI G.
- BLOMGREN H.
- BRODY T.
- BYRT P.
- CINADER B.
- CLAMAN H.N.
- COHEN J.J.
- CRuCHAUD S.
- DARDENNE M.
- DELRIEU F.
- ELSON C.J.
- GOLDSTEIN A.
- Grabar P.
- GREAVFs M.F.
- HUMPHREY J.H.
- ISAKOVId K.
- J F Bach
- JERNE N.K.
- KENNEDY J.C.
- LANCE E.M.
- LIACoPOULOs P.
- MAHIEU P.
- MAKELA O.
- MAKINODAN T.
- MARTIN N.J.
- MASON S.
- MILLER J.F.A.P.
- MITCHISON N.A.
- MOLLER G.
- MONACO A.P.
- MULLER J.Y.
- NISBET N.W.
- NossAL G.J.V.
- NOTA N.R.
- PAPERMASTER B.W.
- PERRUDET-BADOUX A.
- PLAYFAIR J.H.L.
- PLOTZ P.H.
- QUINT J.
- RAFF M.C.
- retardee). BACH
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- REYES F.
- S DAvImE A.J.
- SCHLESINGER M.
- SCHLESINGER M.
- SEGAL S.
- SINGHAL S.K.
- TAUB R.N.
- TAYLOR R.B.
- ToRluoINm G.
- UHR J.W.
- WARNER N.L.
- WIGZELL H.
- WIGZELL H.
- WILSON D.B.
- WORTIS H.H.
- Publication venue
- 'BMJ'
- Publication date
- Field of study
No full textParabiosis in Immunobiology
- Author
- Anderson R. E.
- Ashikawa K.
- Austin CM.
- Bach F. H.
- Bach F.H.
- Bach M.L.
- Bain G. O.
- Barnes D.W.H.
- Barnes D.W.H.
- Bichel J.
- Billingham R. E.
- Billingham R.E.
- Binhammer R. T.
- Binhammer R. T.
- Binhammer R. T.
- Binhammer R.T.
- Braverman I. M.
- Braverman L M.
- Brent L.
- Brent L.
- Brent L.
- Briggs G.W.
- Brumby M.
- Bumet F.M.
- Burnet F. M.
- Carter T.C.
- Chang T.S.
- Cohn Z. A.
- Cornelius E. A.
- Cornelius E. A.
- Cornelius E. A.
- Cornelius E. A.
- Cornelius E. A.
- Dalmasso A. P.
- Damashek W.
- Davis W.E.
- Demant P.
- Dresser D. W.
- Dyke D. C.
- Eichwald E. J.
- Eichwald E. J.
- Eichwald E. J.
- Eichwald E. J.
- Eichwald E.J.
- Elves M.W.
- Elves M.W.
- Feldman J.D.
- Feldmann H.
- Festenstein H.
- Festenstein H.
- Festenstein H.
- Finerty J.C.
- Finerty J.C.
- Fleming D. G.
- Ford C. E.
- Ford C.E.
- Ford W.L.
- Franklin E. C.
- Furth R.
- Girond J.P.
- Good R. A.
- Graff R.J.
- Granger G. A.
- Guttman R. D.
- Hall C. E.
- Hardin C.A.
- Harris J.E.
- Hasek M.
- Hasek M.
- Hayashi T.
- Heslop B.F.
- Hilgard H. R.
- Howard J.G.
- Jaffe W. P.
- Janigan D. T.
- Kilbridge T. M.
- Kinsky R. G.
- Kitamura H.
- Lance E. M.
- Leader article
- Leonard L.
- Leonard L.
- Leonard L.
- Levey R. H.
- Levey R.H.
- Lillie F. R.
- MacGillivray M. H.
- Mansur G. P.
- Marco A. T.
- Mariani T.
- Martinez C.
- Martinez C.
- McBride R. A.
- McBride R. A.
- Miller J. F. A. P.
- Miller J. F. A. P.
- Miller J.F. P. A.
- Moore D.B.
- Myburgh J.A.
- Naeye R. L.
- Nakic B.
- Nakic B.
- Nakic B.
- Nakic B.
- Nisbet N. W.
- Nisbet N.W.
- Nisbet N.W.
- Owen R. D.
- Pope R. S.
- Pope R. S.
- Pope R. S.
- Rodey G.E.
- Roser B.
- Rubin B. A.
- Ryan G.B.
- Rychlikova M.
- Salaman J. R.
- Shapiro E. C.
- Simonsen M.
- Simonsen M.
- Simonsen M.
- Skowron-Cendrzak A.
- Skowron-Cendrzak A.
- Skowron-Cendrzak A.
- Snell G. D.
- Snell G. D.
- Snell G.D.
- Sodicoff M.
- Strober S.
- Talal N.
- Tokuda S.
- Tyler R. W.
- Voisin G. A.
- Voisin G. A.
- Volkman A.
- Walford R. L.
- Walford R. L.
- Walford R. L.
- Wilson D. B.
- Yunis E. J.
- Zaleski M.
- Zaleski M.
- Publication venue
- 'Wiley'
- Publication date
- Field of study
No full textRegulation of Delayed Type Hypersensitivity to Host Histocompatibility Antigens during Graft-versus-Host Reactions
- Author
- Ahmed A.
- Altmann D.M.
- Argyris B.F.
- Bach B.A.
- Bekkum D.W.
- Bekkum D.W.
- Benner R.
- Benner R.
- Bianchi A.T.J.
- Bianchi A.T.J.
- Bianchi A.T.J.
- Bianchi A.T.J.
- Blanden R.V.
- Bloom B.R.
- Boak J.L.
- Borland A.
- Brent L.
- Bril H.
- Bril H.
- Bril H.
- Bril H.
- Bril H.
- Cantor H.
- Cheung H.T
- Colizzi V.
- Elkins W.L.
- Elkins W.L.
- Festenstein H.
- Gershon R.K.
- Gershon R.K.
- Gill H.K.
- Grebe S.C.
- Guiot H.F.L.
- Haile-Pannenko O.
- Halle-Pannenko O.
- Hamilton B.L.
- Holan V.
- Howard J.G.
- Huber B.
- Jadus M.R.
- Jadus M.R.
- Jones T.D.
- Komgold R.
- Kubota E.
- Kwast Th.H.
- Lagrange PH.
- Liew F.Y.
- Liew F.Y.
- Mason D.W.
- Miller S.D.
- Mowat A.Me.I.
- Nelson D.S.
- Nisbet N.W.
- Okazaki H.
- Okunewick J.P.
- Pattengale P.
- Pickel K.
- Pritchard L.L.
- Raff M.C.
- Raff M.C.
- Rose W.C
- Schreier M.H.
- Schreier M.H.
- Shand F.L.
- Simonsen M.
- Simpson E.
- Smith F.
- Smith K.A.
- Sprent J.
- Storb R.
- Sy M.S.
- Vriesendorp H.M.
- Waal L.P.
- Widmer M.B.
- Winchurch R.A.
- Wolters E.A.J.
- Wolters E.A.J.
- Wolters E.A.J.
- Zurcher C.
- Publication venue
- 'Wiley'
- Publication date
- Field of study
No full textPolitical Communication Theory and Research: An Overview
- Author
- ABELSON H.I.
- ALMOND G.
- American Institute for Political Communication
- ATKIN C.
- BARBER J.D.
- BAUER R.A.
- BECKER L.B.
- BELL D.V.J.
- BERELSON B.R.
- BLANCHARD R.O.
- BLUMER H.
- BLUMLER J.G.
- BRODY R.A.
- BRYCE J.
- BURKE K.
- BURKE K.
- CAMPBELL A.
- CAMPBELL A.
- CAMPBELL A.
- CAREY J.W.
- CAREY J.W.
- CHAFFEE S.
- CHITTICK W.O.
- COBB R.W.
- CZUDNOWSKI M.M.
- DAHL R.A.
- DAVISON W.P.
- DENNIS J.
- DEUTSCH K.W.
- DEUTSCH K.W.
- DEVINE D.J.
- DEWEY J.
- DOOB L.W.
- DOOB L.W.
- DOWNS A.
- DUNCAN H.D.
- DYE T.R.
- EASTON D.
- EASTON D.
- EDELMAN M.
- EDELSTEIN A.S.
- ELAZAR D.J.
- ELDERSVELD S.J.
- ELLUL J.
- EPSTEIN E.J.
- ETZONI A.
- FAGEN R.R.
- GORDON G.
- GRABER D.A.
- GRABER D.A.
- GUSFIELD J.R.
- HAWLEY W.D.
- HESS R.D.
- HIMMELSTRAND J.
- HOYER S.
- JENNINGS M.K.
- KAID L.L.
- KATZ E.
- KATZ E.
- KATZ E.
- KATZ E.
- KESSEL J.H.
- KESSEL J.H.
- KLAPP O.E.
- KLAPPER J. T.
- KRIEGHBAUM H.
- LASSWELL H.D.
- LASSWELL H.D.
- LAZARSFELD P.
- LIPPMANN W.
- LUTTBEG N.R.
- McCOMBS M.
- McGUIRE W.J.
- MEAD G.H.
- MENDELSOHN H.
- MILLER G.A.
- MINOW N.W.
- MUELLER C.
- MUELLER J.E.
- NAPOLITAN J.
- NIMMO D.
- NIMMO D.
- NISBET R.
- PATTERSON T.E.
- POMPER G.
- RIVERS W.
- RIVERS W.
- ROBINSON W.P.
- ROSENAU J.N.
- ROSENGREN K.E.
- ROSHCO B.
- ROSTEN L.C.
- ROTHSCHILD M.L.
- ROURKE F.E.
- SAPIR E.
- SCHILLER H.I.
- SEARS D.O.
- SEIDEN M.H.
- SEYMOUR-URE C.
- SIGAL L.V.
- STEPHENSON W.
- STOGDILL R.M
- TUNSTALL J.
- VERBA S.
- WASBY S.L.
- WEISS W.
- WOLFENSTEIN E.V.
- WYCKOFF G.
- Publication venue
- 'Informa UK Limited'
- Publication date
- Field of study
No full textGenome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes
- Author
- Abecasis G. (Goncalo)
- Abecasis G.R. (Gonçalo)
- Abecasis G.R. (Gonçalo)
- Aben K.K.H. (Katja)
- Absher D. (Devin)
- Absher D. (Devin)
- Aherrahrou Z. (Zouhair)
- Ahlqvist E. (Emma)
- Ahmadi K.R. (Kourosh)
- Ahmed N. (Nabeel)
- Alavere H. (Helene)
- Alibrandi M.T.S. (Maria)
- Allayee H. (Hooman)
- Allen H.L.
- Almgren P. (Peter)
- Altshuler D. (David)
- Amin N. (Najaf)
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- Wingerden S. (Sophie) van
- Winkler T.W. (Thomas W.)
- Witte D.R. (Daniel R.)
- Witte D.R. (Deniel)
- Witteman J. (Jacqueline)
- Witteman J.C.M. (Jacqueline)
- Witteman J.C.M. (Jaqueline C.M.)
- Wood A.R. (Andrew)
- Workalemahu T. (Tsegaselassie)
- Wright A.F. (Alan)
- Wright B.J. (Benjamin)
- Wu G. (Guanming)
- Xie W. (Weijia)
- Xu J. (Jianfeng)
- Yang J. (Jian)
- Yang J. (Joanna)
- Yang T.-P. (Tsun-Po)
- Ye S. (Shu)
- Zabena C. (Carina)
- Zaidi M.A. (Aghar)
- Zaman K.S. (Khan Shah)
- Zeggini E. (Eleftheria)
- Zeller T. (Tanja)
- Zethelius B. (Björn)
- Zgaga L. (Lina)
- Zhang Q. (Qunyuan)
- Zhang W. (Weihua)
- Zhao J.H. (Jing Hua)
- Ziegler A. (Andreas)
- Ziegler A. (Andreas)
- Zillikens M.C. (Carola)
- Zitting P. (Paavo)
- Zondervan K.T. (Krina T.)
- Zondervan K.T. (Krina)
- Zwart J-A. (John-Anker)
- Öhrvik J. (John)
- Östenson C.-G. (Claes-Göran)
- Publication venue
- Publication date
- 01/10/2011
- Field of study
Get PDFOBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS - We have conducted a meta-analysis of genome-wide association tests of ;2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS - Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10-8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/ C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 3 10-4), improved b-cell function (P = 1.1 × 10-5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10-6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS - We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis
A Bibliography of Australian Paediatrics 1846–1900 PART III
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- Publication date
- Field of study
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