3 research outputs found
Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index
- Author
- Adamo P. (Pio) d'
- Adan R. (R.)
- Alavere H. (Helene)
- Albrecht E. (Eva)
- Alexander G. (Graeme)
- Alfredsson L. (Lars)
- Amin N. (Najaf)
- Amin N. (Najaf)
- Anderson C.A. (Carl A)
- Ando T. (Tetsuya)
- Ang W.Q. (Wei)
- Antel J. (J.)
- Aspelund T. (T.)
- Aspelund T. (Thor)
- Atalay M. (Mustafa)
- Baker J.H. (Jessica H)
- Barrett J.C. (Jeffrey)
- Barroso I.E. (InĂȘs)
- Beijsterveldt C.E.M. (Toos) van
- Bencko V. (Vladimir)
- Benke K. (K.)
- Berenson G. (Gerald)
- Bergen A.W. (Andrew)
- Bergen N. (N.)
- Bergmann S.M. (Sven)
- Berrettini W. (Wade)
- Berry D. (Diane)
- Bierut L.J. (L. J.)
- Bierut L.J. (Laura)
- Blackburn H. (Hannah)
- Boerwinkle E. (E.)
- Boerwinkle E.A. (Eric)
- Boni C. (Claudette)
- Boomsma D.I. (Dorret)
- Boraska Perica V. (V.)
- Boyd H.A. (H. A.)
- Bradfield J.P. (Jonathan)
- Brandys M. (M.)
- Breen G. (Gerome)
- Breen G. (Gerome)
- Bruson A. (Alice)
- Bulik C.M. (C. M.)
- Burghardt R. (Roland)
- Buring J.E. (Julie)
- Busonero F.
- Busonero F. (F.)
- Byrne E.M. (E. M.)
- Byrne E.M. (Enda)
- BĂŒhren K. (Katharina)
- Carlberg L. (Laura)
- Chanock S.J. (S. J.)
- Chanock S.J. (Stephen)
- Charoen P. (Pimphen)
- Chasman D.I. (Daniel)
- Cichon S. (Sven)
- Clementi M. (Maurizio)
- Cohen-Woods S. (Sarah)
- Coin L. (Lachlan)
- Collier D.A. (David)
- Cone R.D. (Roger D)
- Conlon P. (Peter)
- Conlon P.J. (Peter J)
- Cooper C. (C.)
- Cooper C. (Charles)
- Cornelis M. (Marilyn)
- Corre T. (Tanguy)
- Couper D.J. (David)
- Cousminer D.L. (Diana)
- Coviello A.D. (Andrea)
- Crawford S. (Steve)
- Crisponi L. (Laura)
- Crow S. (Scott)
- Danner U.N. (Unna N)
- Das S. (Shikta)
- Davey Smith G. (G.)
- Davis O.S.P. (Oliver S.)
- de Geus E.J. (E. J.)
- de Kove C. (Carolien)
- De Zwaan M. (M.)
- Dedoussis G.V. (G. V.)
- Dedoussis G.V. (George)
- Degortes D. (Daniela)
- Deloukas P. (Panagiotis)
- Demerath E.W. (E. W.)
- Demerath E.W. (Ellen)
- DeSocio J.E. (Janiece E)
- Dick D.M. (Danielle)
- Dmitrzak-Weglarz M. (Monika)
- Docampo E. (Elisa)
- Dominiczak A. (Anna)
- Dominiczak A. (Anna)
- Duijn C.M. (Cornelia) van
- Duncanson A. (Audrey)
- Döring A. (Angela)
- Econs M.J. (M. J.)
- Econs M.J. (Michael)
- Edkins T. (Ted)
- Egberts K. (Karin)
- Ehrlich S.M. (Stefan)
- Eiriksdottir G. (Gudny)
- Elburg A.A. (Annemarie) van
- Elks C.E. (Cathy)
- Elliott P. (P.)
- Elliott P. (Paul)
- Esko T. (T.)
- Esko T. (TÔnu)
- Espeseth T. (Thomas)
- Estivill X. (Xavier)
- Evans D.M. (D. M.)
- Faire U. (Ulf) de
- Farmer A.E. (Anne E)
- Favaro A. (Angela)
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- Feenstra B. (Bjarke)
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- Föcker M. (M.)
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- Garcia M.E. (M.)
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- Geus E.J.C. (Eco) de
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- Gillman M.W. (Matthew W.)
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- Gorwood P. (Philip)
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- Gudbjartsson D.F. (Daniel)
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- Guxens Junyent M. (MĂČnica)
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- KilpelÀinen T.O. (Tuomas)
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- Middeldorp C.M. (Christel)
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- Parker A.N. (Alex)
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- Ritchie G.R.S. (Graham R.S.)
- Rivadeneira Ramirez F. (Fernando)
- Rivadeneira F. (F.)
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- Rodriguez A. (A.)
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- Rujescu D. (Dan)
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- Scherer S.W. (Stephen W)
- Scherer S.W. (Stephen)
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- Sladek R. (Rob)
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- Slof-Opât Landt M.C.T. (Margarita C. T.)
- Slopien A. (Agnieszka)
- Smith A.V. (Albert)
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- Smith A.V. (Davey)
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- Srinivasan S.R. (Sathanur)
- Steen V.M. (Vidar)
- Stephens J. (Jonathan)
- Stolk L. (Lisette)
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- Streeten E.A. (Elizabeth)
- Strengman E. (Eric)
- Strober M. (Michael)
- Sulem P. (Patrick)
- Sullivan P.F. (Patrick)
- Sunyer J. (J.)
- Sunyer J. (Jordi)
- Szatkiewicz J.P. (Jin P)
- Szeszenia-Dabrowska N. (Neonila)
- SĂžrensen T.I.A. (Thorkild)
- Taal H.R. (Rob)
- Tachmazidou I. (Ioanna)
- Taico C. (Chrysecolla)
- Tammesoo M.L. (M. L.)
- Tenconi E. (Elena)
- Teo Y.Y. (Y. Y.)
- Teo Y.Y. (Yik Ying)
- Thiering E. (Elisabeth)
- Thornton L.M. (Laura)
- Thorsteinsdottir U. (Unnur)
- Tiesler C. (C.)
- Tikkanen E. (Emmi)
- Timpson N.J. (Nicholas)
- Toniolo D. (Daniela)
- Tortorella A. (Alfonso)
- Tozzi F. (Federica)
- Trace S.E. (Sara E)
- Treasure J. (Janet)
- Tryggvadottir L. (Laufey)
- Tschop M. (Matthias)
- Tschöp M.H. (M. H.)
- Tsitsika A. (Artemis)
- Tsitsika A. (Artemis)
- Tyrer J. (J.)
- Tziouvas K. (Konstantinos)
- Uda M. (M.)
- Uitterlinden A.G. (André)
- Ulivi S. (Shelia)
- ValcĂĄrcel B. (Beatriz)
- van Dam R.M. (R. M.)
- Vannberg F.O. (Frederik O)
- Versini A. (Audrey)
- Visser J.A. (Jenny)
- Volckmar A.-L. (A. L.)
- Vollenweider P. (Peter)
- Waeber G. (GĂ©rard)
- Wagner G. (Gudrun)
- Wareham N.J. (Nick)
- Warrington M. (M.)
- Warrington N.M. (Nicole)
- Waterworth D. (Dawn)
- Weedon M.N. (Michael)
- White S.J. (Stefan)
- Whittaker P. (Pamela)
- Wichmann H.E. (Heinz Erich)
- Widen E.
- Widen E. (E.)
- Willemsen G.A.H.M. (Gonneke)
- Wilson J.F. (J. F.)
- Wingerden S. (Sophie) van
- Winkler T.W. (Thomas W.)
- Woodside D.B. (D Blake)
- Wright A.F. (Alan)
- Yaghootkar H. (H.)
- Yilmaz Z. (Zeynep)
- Young L. (L.)
- Zeggini E. (Eleftheria)
- Zerwas S. (Stephanie)
- Zgaga L. (L.)
- Zhai G. (G.)
- Zhao J.H. (J. H.)
- Zhuang W.V. (W. V.)
- Zipfel S. (S.)
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/02/2017
- Field of study
The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 Ă 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 Ă 10-06/Pfemales: 3.45 Ă 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation
Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals
- Author
- Abecasis G.R. (Goncalo R.)
- Abecasis G.R. (Goncalo R.)
- Abecasis G.R. (Gonçalo R.)
- Abecasis G.R. (Gonçalo)
- Adair L.S. (Linda)
- Allison M.A. (Matthew)
- Altshuler D. (David)
- Altshuler D. (David)
- Amin N. (Najaf)
- An P. (Ping)
- Ardlie K.G. (Kristin)
- Ardlie K.G. (Kristin)
- Ariyurek Y. (Yavuz)
- Aulchenko Y.S. (Yurii S.)
- Aulchenko Y.S. (Yurii S.)
- Aulchenko Y.S. (Yurii)
- Bacquer O.L. (Olivier)
- Balkau B. (Beverley)
- Balkau B. (Beverley)
- Ballantyne C. (Christie)
- Ballantyne C.M. (Christie M.)
- Ballantyne C.M. (Christie M.)
- Bandinelli S. (Stefania)
- Bandinelli S. (Stefania)
- Barbalic M. (maja)
- Barroso I.
- Barroso I.E. (InĂȘs)
- Barroso I.E. (InĂȘs)
- Barter P. (Phil)
- Beekman M. (Marian)
- Beilby J.P. (John)
- Ben-Shlomo Y.
- Benediktsson R. (Rafn)
- Benediktsson R. (Rafn)
- Bennett A.J. (Amanda)
- Bennett A.J. (Amanda)
- Bergman R.N. (Richard N.)
- Bergman R.N. (Richard N.)
- Bergman R.N. (Richard N.)
- Bergmann S.M. (Sven)
- Bidulescu A. (Aurelian)
- Bis J.C. (Joshua)
- Blagieva R. (Roza)
- Bochud M. (Murielle)
- Boehm B.O. (Bernhard)
- Boehnke M. (Michael)
- Boehnke M. (Michael)
- Boehnke M. (Michael)
- Boekholdt S.M. (Matthijs)
- Boerwinkle E. (Eric)
- Boerwinkle E. (Eric)
- Boerwinkle E.A. (Eric)
- Bonnefond A. (Amélie)
- Bonnycastle L.L. (Lori L.)
- Bonnycastle L.L. (Lori L.)
- Bonnycastle L.L. (Lori)
- Boomsma D.I. (Dorret I)
- Boomsma D.I. (Dorret I.)
- Boomsma D.I. (Dorret)
- Borch-Johnsen K.
- Borecki I.B. (Ingrid B)
- Borja J.B. (Judith)
- Boström K.B. (Kristina Bengtsson)
- Bouatia-Naji N. (Nabila)
- Bravenboer B. (Bert)
- Brunner E. (Eric)
- Buchanan T.A. (Thomas)
- Bumpstead S. (Suzannah)
- Bumpstead S. (Suzannah)
- Burtt N.P. (Noël P.)
- Burtt N.P. (Noël)
- Buxbaum S.G. (Sarah)
- Böhringer S. (Stefan)
- Böttcher Y. (Yvonne)
- Campbell H. (Harry)
- Campbell H. (Harry)
- Campbell H. (Harry)
- Cao A. (Antonio)
- Carlson O.D. (Olga)
- Cauchi S. (Stephane)
- Caulfield M. (Mark)
- Caulfield M.J. (Mark J.)
- Cavalcanti-Proença C. (Christine)
- Chambers J. (John)
- Chambers J.C. (John C.)
- Charpentier G. (Guillaume)
- Charpentier G. (Guillaume)
- Chasman D.I. (Daniel)
- Chen I. (Ida)
- Chen Y.-D.I. (Yii-Der Ida)
- Chen Y.D.I. (Yii-Der Ida)
- Chines P.S. (Peter S.)
- Chines P.S. (Peter)
- Cho Y.S. (Yoon Shin)
- Clarke R. (Robert)
- Coassin S. (Stefan)
- Coin L. (Lachlan)
- Collins F.S. (Francis S.)
- Collins F.S. (Francis S.)
- Collins F.S. (Francis)
- Cooper C. (Charles)
- Cooper C. (Cyrus)
- Cooper M.N. (Matthew)
- Cornelis M. (Marilyn)
- Cornelis M. (Marilyn)
- Couper D.J. (David J.)
- Couper D.J. (David)
- Crawford G. (Gabe)
- Crawford G. (Gabe)
- Crawford G. (Gabriel)
- Crisponi L. (Laura)
- Croteau-Chonka D.C. (Damien)
- Daly M.J. (Mark)
- Dam R.M. (Rob) van
- Dastani Z. (Zari)
- Day I.N.M. (Ian)
- Dedoussis G.V. (George)
- Dehghan A. (Abbas)
- Deloukas P. (Panagiotis)
- Deloukas P. (Panagiotis)
- Delplanque J. (Jerome)
- DIAGRAM+ Consortium
- Dina C. (Christian)
- Dina C. (Christian)
- Dominiczak A. (Anna)
- Dominiczak A.F. (Anna F.)
- Doney A.S.F. (Alex S. F.)
- Doney A.S.F. (Alex)
- Duijn C.M. (Cornelia) van
- Duncan B.B. (Bruce)
- Dupuis J. (Josée)
- Dupuis J. (Josée)
- Dupuis J. (Josée)
- Döring A. (Angela)
- Ebrahim S. (Shanil)
- Egan J.M. (Josephine)
- Egan J.M. (Josephine)
- Ejebe K.G. (Kenechi)
- Elliott A.L. (Amanda)
- Elliott A.L. (Amanda)
- Elliott K.S. (Katherine)
- Elliott P. (Paul)
- Erdmann J. (Jeanette)
- Erdmann J. (Jeanette)
- Erdos M.R. (Michael)
- Erdos M.R. (Michael)
- Evans D.M. (David)
- Faire U. (Ulf) de
- Fedson A.C. (Annette)
- Feitosa M.F. (Mary Furlan)
- Ferreira T. (Teresa)
- Ferrucci L. (Luigi)
- Ferrucci L. (Luigi)
- Fischer-Rosinsky A. (Antje)
- Florez J.C. (Jose C.)
- Florez J.C. (Jose)
- Florez J.C. (Jose)
- Forouhi N.G. (Nita)
- Fouchier S.W. (Sigrid)
- Fox C.S. (Caroline)
- Fox C.S. (Caroline)
- Franklin C.S. (Christopher)
- Franklin C.S. (Christopher)
- Franks P.W. (Paul)
- Frants R. (Rune)
- Frants R.R. (Rune)
- Franzosi M.
- Frayling T.M. (Timothy M.)
- Frayling T.M. (Timothy M.)
- Frayling T.M. (Timothy M.)
- Frayling T.M. (Timothy)
- Froguel P. (Philippe)
- Froguel P. (Philippe)
- Fuchsberger C. (Christian)
- Gabriel S.B. (Stacey)
- Galan P. (Pilar)
- Ganser M. (Martha)
- Garcia M.E. (M.)
- Geus E.J.C. (Eco) de
- Gieger C. (Christian)
- Gieger C. (Christian)
- Gieger C. (Christian)
- Gieger C. (Christian)
- Glazer N.L. (Nicole)
- GLGC Investigators
- Gloyn A.L. (Anna L.)
- Gloyn A.L. (Anna)
- Go M.J. (Min Jin)
- Goel A. (Anuj)
- Gonzalez E. (Elena)
- Goodarzi M. (Mark)
- Graessler J. (JĂŒrgen)
- Grallert H. (Harald)
- Grallert H. (Harald)
- Grarup N. (Niels)
- Grarup N. (Niels)
- Green T. (Todd)
- Greenwood C.M.T. (Celia)
- Griffin S. (Simon)
- Grimsby J. (Jonna)
- Groop L. (Leif)
- Groop L. (Leif)
- Groop L. (Leif)
- Groves C.J. (Christopher)
- Groves C.J. (Christopher)
- Grundy S.M. (Scott)
- Gudnason V. (Vilmundur)
- Guiducci C. (Candace)
- Guiducci C. (Candace)
- Guo X. (Xiuqing)
- Guo X. (Xiuqing)
- Gwilliam R. (Rhian)
- Gyllensten U. (Ulf)
- Gyllensten U. (Ulf)
- Gyllensten U. (Ulf)
- Hadjadj S. (Samy)
- Hadjadj S. (Samy)
- Haeften T.W. (Timon) van
- Hagen K. (Knut)
- Hall A.S. (Alistair)
- Hallmans G. (Göran)
- Hammond N. (Naomi)
- Hamsten A. (Anders)
- Han X. (Xijing)
- Hansen T. (Torben)
- Haritunians T. (Talin)
- Harris T.B. (Tamara B.)
- Harris T.B. (Tamara)
- Hartikainen A.L.
- Hassanali N. (Neelam)
- Hassanali N. (Neelam)
- Hastie N. (Nick)
- Hattersley A.T. (Andrew)
- Haun M. (Margot)
- Havulinna A.S. (Aki)
- Hayward C.
- Hayward C. (Caroline)
- Heath S.C. (Simon)
- Heemst D. (Diana) van
- Hegele R.A. (Robert)
- Heid I.M. (Iris)
- Heid I.M. (Iris)
- Hengstenberg C. (Christian)
- Henneman P. (Peter)
- Henneman P. (Peter)
- Hercberg S. (Serge)
- Herder C. (Christian)
- Herder C. (Christian)
- Herpt T.W. (Thijs) van
- Hicks A.A. (Andrew A.)
- Hicks A.A. (Andrew)
- Hide W.A. (Winston)
- Hillman D.R. (David)
- Hingorani A. (Aroon)
- Hitman G.A. (Graham)
- Hivert M.-F. (Marie-France)
- Hoek M. (Mandy) van
- Hofman A.
- Hofman A. (Albert)
- Hofman A. (Albert)
- Hofman A. (Albert)
- Hofmann O.M. (Oliver)
- Holm H. (Hilma)
- Hottenga J.J. (Jouke Jan)
- Hottenga J.J. (Jouke Jan)
- Hovingh G.K. (Kees)
- Hu F.B. (Frank B)
- Hu F.B. (Frank B.)
- Hu F.B. (Frank)
- Hui J. (Jennie)
- Hung J. (Joe)
- Hunter D.J. (David)
- Huth C. (Cornelia)
- Hveem K. (Kristian)
- Igl W. (Wilmar)
- Illig T. (Thomas)
- Illig T. (Thomas)
- Ingelsson E. (Erik)
- Ingelsson E. (Erik)
- Ingelsson E. (Erik)
- Isaacs A. (Aaron)
- Isaacs A.J. (Aaron)
- Isomaa B. (Bo)
- Isomaa B. (Bo)
- Jackson A.U. (Anne)
- Jackson A.U. (Anne)
- Jarvelin M.-R. (Marjo-Riitta)
- Jarvelin M.-R. (Marjo-Riitta)
- Jarvelin M.-R. (Marjo-Riitta)
- Johansen C.T. (Christopher)
- Johansson A. (Ă sa)
- Johnson P.R.V. (Paul R. V.)
- Johnson P.R.V. (Paul)
- Johnson T. (Toby)
- Johnson T. (Toby)
- Johnson T. (Toby)
- Jorgensen T. (Torben)
- Jorgensen T. (Torben)
- Jula A. (Antti)
- Jula A. (Antti)
- Kaakinen M. (Marika)
- Kanaya A. (Alka)
- Kanoni S. (Stavroula)
- Kanoni S. (Stavroula)
- Kao W.H.L. (W. H. Linda)
- Kao W.H.L. (Wen H. L.)
- Kao W.H.L. (Wen)
- Kao W.H.L. (Wen)
- Kaplan L. (Lee)
- Kaprio J. (Jaakko)
- Kapur K. (Karen)
- Karpe F. (Fredrik)
- Kastelein J.J.P. (John)
- Katsareli E. (Efi)
- Kedenko L. (Lyudmyla)
- Kesaniemi Y.A. (Antero)
- Khaw K.-T. (Kay-Tee)
- Khaw K.T.
- Kim Y-J. (Yong-Jin)
- Kim Y.J.
- Kivimaki M. (Mika)
- Kizer J.R. (Jorge)
- Klopp N. (Norman)
- Klopp N. (Norman)
- Kloppenburg M. (Margreet)
- Knight B. (Beatrice)
- Kong A. (Augustine)
- Kong A. (Augustine)
- Kooner J. (Jaspal)
- Koseki M. (Masahiro)
- Koskinen S. (Seppo)
- Kovacs P. (Peter)
- Kraft P. (Peter)
- Kristiansson K. (Kati)
- Kronenberg F. (Florian)
- Kronenberg F. (Florian)
- Kumari M. (Meena)
- Kuusisto J. (Johanna)
- Kuzawa C.W. (Christopher W.)
- Kuzawa C.W. (Christopher)
- Kyvik K.O. (Kirsten O.)
- Kyvik K.O. (Kirsten Ohm)
- KÀhönen M. (Mika)
- König I.R. (Inke)
- Laakso M. (Markku)
- Laakso M. (Markku)
- Laakso M. (Markku)
- Laaksonen R. (Reijo)
- Ladouceur M. (Martin)
- Lajunen T. (Taina)
- Lakatta E.G. (Edward G.)
- Lamina C. (Claudia)
- Lamina C. (Claudia)
- Lange L.A. (Leslie)
- Lange L.A. (Leslie)
- Langenberg C. (Claudia)
- Langenberg C. (Claudia)
- Langenberg C. (Claudia)
- Langenberg C. (Claudia)
- Lathrop G. (GMark)
- Launer L.J. (Lenore J.)
- Lauritzen T. (Torsten)
- Lawlor D.A. (Debbie)
- Lecoeur C. (CĂ©cile)
- Lee J.-Y. (Jong-Young)
- LehtimÀki T. (Terho)
- Lettre G. (Guillaume)
- Li M. (Man)
- Li M. (Man)
- Li X. (Xiaohui)
- Li X. (Xiaohui)
- Li Y. (Yun)
- Lieverse A.G. (Aloysius)
- Lindgren C.M. (Cecilia M.)
- Lindgren C.M. (Cecilia)
- Liu C.-T. (Ching-Ti)
- Liu Y. (YongMei)
- Lohman K. (Kurt)
- Lokki M.L.
- Loo B.-M. (Britt-Marie)
- Loos R.J.F. (Ruth)
- Loos R.J.F. (Ruth)
- Loos R.J.F. (Ruth)
- Luan J. (Jianâan)
- Luan J. (Jianâan)
- Luben R.N. (Robert)
- Lucas G. (Gavin)
- Lyssenko V. (Valeriya)
- Lyssenko V. (Valeriya)
- LyytikÀinen L.-P. (Leo-Pekka)
- MAGIC Consortium
- Magnusson P.K. (Patrik)
- Magnusson P.K.E. (Patrik K. E.)
- Mahley R. (Robert)
- Mangino M. (Massimo)
- Mangino M. (Massimo)
- Manning A.K. (Alisa K.)
- Manning A.K. (Alisa)
- Marmot M. (Michael)
- Marre M. (Michel)
- Marroni F. (Fabio)
- Martin N.G. (Nicholas)
- Martinez-Larrad M.T. (Maria Teresa)
- Masson D. (David)
- McArdle W.L. (Wendy)
- McAteer J.B. (Jarred)
- McCarroll S.A. (Steve)
- McCarroll S.A. (Steven)
- McCarthy M.I. (Mark I.)
- McCarthy M.I. (Mark I.)
- McCarthy M.I. (Mark)
- McCulloch L.J. (Laura J.)
- McCulloch L.J. (Laura)
- McPherson R. (Ruth)
- Meigs J.B. (James B.)
- Meigs J.B. (James)
- Meigs J.B. (James)
- Meisinger C. (Christa)
- Meitinger T. (Thomas)
- Meitinger T. (Thomas)
- Meitinger T. (Thomas)
- Melander O. (Olle)
- Melzer D. (David)
- Meneton P. (Pierre)
- Meulenbelt I. (Ingrid)
- Meyre D. (David)
- Midthjell K. (Kristian)
- Mitchell B.D. (Braxton)
- Mohlke K.L. (Karen L.)
- Mohlke K.L. (Karen L.)
- Mohlke K.L. (Karen L.)
- Mohlke K.L. (Karen)
- Mooser V. (Vincent)
- Mooser V. (Vincent)
- Mooser V.E. (Vincent E.)
- Morken M.A. (Mario A.)
- Morken M.A. (Mario)
- Morris A.D. (Andrew D.)
- Morris A.D. (Andrew)
- Morris A.P. (Andrew P.)
- Morris A.P. (Andrew P.)
- Morris A.P. (Andrew)
- Mukherjee S. (Sutapa)
- Munroe P. (Patricia)
- Musani S. (Solomon)
- Musunuru K. (Kiran)
- MuTHER Consortium
- MĂ€gi R. (Reedik)
- Naitza S. (Silvia)
- Narisu N. (Narisu)
- Narisu N. (Narisu)
- Nathan D.M. (David)
- Navarro P. (Pau)
- Navarro P. (Pau)
- Neville M.J. (Matthew)
- Nickerson D.A. (Deborah A.)
- Nickerson D.A. (Deborah)
- Nieminen M.S. (Markku)
- Nilsson P. (Peter)
- Nuotio M.-L. (Marja-Liisa)
- Oostra B.A. (Ben A.)
- Oostra B.A. (Ben)
- Oostra B.A. (Ben)
- Ordovas J.M. (Jose M.)
- Ordovas J.M. (Jose)
- Orho-Melander M. (Marju)
- OrrĂč M. (Marco)
- Owen K.R. (Katharine)
- OâConnell J. (Jeffrey)
- Pakyz R. (Ruth)
- Palmer C. (Cameron)
- Palmer C.N.A. (Colin N. A.)
- Palmer C.N.A. (Colin)
- Pankow J.S. (James S.)
- Pankow J.S. (James)
- Paolisso G. (Giuseppe)
- Pare G. (Guillame)
- Park T. (Taesung)
- Parker A.N. (Alex)
- Pattaro C. (Cristian)
- Pattaro C. (Cristian)
- Pattou F. (François)
- Paulweber B. (Bernhard)
- Payne F. (Felicity)
- Payne F. (Felicity)
- Pearson D. (Daniel)
- Peden J. (John)
- Pedersen N.L. (Nancy)
- Pedersen O. (Oluf)
- Pedersen O. (Oluf)
- Peloso G.M. (Gina)
- Peltonen L. (Leena Johanna)
- Penninx B.W.J.H.
- Penninx B.W.J.H. (Brenda W. J. H.)
- Penninx B.W.J.H. (Brenda)
- Perola M. (Markus)
- Perola M. (Markus)
- Perola M. (Markus)
- Perry J.R.B. (John R. B.)
- Perry J.R.B. (John R. B.)
- Perry J.R.B. (John)
- Petersen A.K.
- Pfeiffer A.F.H. (Andreas)
- Pichler I. (Irene)
- Pichler I. (Irene)
- Platou C.P. (Carl)
- Polasek O. (Ozren)
- Posthuma D. (Danielle)
- Potter S.C. (Simon)
- Pouta A. (Anneli)
- Pramstaller P.P. (Peter P.)
- Pramstaller P.P. (Peter P.)
- Pramstaller P.P. (Peter Paul)
- Pramstaller P.P. (Peter Paul)
- Proença C. (Christine)
- Prokopenko I. (Inga)
- Prokopenko I. (Inga)
- Province M.A. (Mike)
- Psaty B.M. (Bruce M.)
- Psaty B.M. (Bruce)
- Qi L. (Lu)
- Qi L. (Lu)
- Quertermous T. (Thomas)
- Quertermous T. (Thomas)
- Rader D.J. (Daniel)
- Raitakari O. (Olli)
- Randall J.C. (Joshua)
- Rasmussen-Torvik L.J. (Laura)
- Rathmann W. (Wolfgang)
- Rathmann W. (Wolfgang)
- Raychaudhuri S. (Soumya)
- Rayner N.W. (Nigel W.)
- Rayner N.W. (Nigel William)
- Redline S. (Susan)
- Reilly M.P. (Muredach P.)
- Rice K.M. (Kenneth)
- Richards J.B. (J. Brent)
- Ricketts S.L. (Sally)
- Ridker P.M. (Paul)
- Rieder M. (Mark)
- Rieder M. (Mark)
- Ripatti S. (Samuli)
- Ripatti S. (Samuli)
- Rivadeneira Ramirez F. (Fernando)
- Roberts R. (Robert)
- Robertson N.R. (Neil)
- Roccasecca R.M.
- Rocheleau G. (Ghislain)
- Rocheleau G. (Ghislain)
- Roden M. (Michael)
- Roden M. (Michael)
- Rolandsson O. (Olov)
- Rose L.M. (Lynda)
- Rotter J.I. (Jerome I)
- Rudan I. (Igor)
- Rudan I. (Igor)
- Rudan I. (Igor)
- Ruokonen A. (Aimo)
- Ruokonen A. (Aimo)
- Rybin D. (Denis)
- Sabatti C. (Chiara)
- Saharinen J. (Juha)
- Salomaa V. (Veikko)
- Salomaa V. (Veikko)
- Salomaa V. (Veikko)
- Samani N.J. (Nilesh)
- Samani N.J. (Nilesh)
- Sampson M.J. (Michael J)
- Sampson M.J. (Michael)
- Sandbaek A. (Annelli)
- Sandhu M. (Manjinder)
- Sandhu M.S. (Manjinder)
- Sanna S. (Serena)
- Sanna S. (Serena)
- Sattar N. (Naveed)
- Saxena R. (Richa)
- Saxena R. (Richa)
- Sayer A.A.
- Schadt E.E. (Eric E.)
- Schadt E.E. (Eric)
- Scheet P. (Paul)
- Schlessinger D. (David)
- Schlessinger D. (David)
- Schunkert H. (Heribert)
- Schwarz P.E.H. (Peter)
- Scott L.J. (Laura J.)
- Scott L.J. (Laura)
- Scott R.A. (Robert)
- Scuteri A. (Angelo)
- Scuteri A. (Angelo)
- Scuteri A. (Angelo)
- Seedorf U. (Udo)
- SegrĂš A.V. (Ayellet)
- Seielstad M. (Mark)
- Semple R.K. (Robert K.)
- Serrano-RĂos M. (Manuel)
- Sethupathy P. (Praveen)
- Sharp S.J. (Stephen)
- Shields B.M. (Beverley)
- Shields B.M. (Beverley)
- Shrader P. (Peter)
- Shrader P. (Peter)
- Shuldiner A.R. (Alan)
- Sigurdsson G. (Gunnar)
- Sigursson G. (Gunnar)
- Sijbrands E. (Eric)
- Sijbrands E.J.G. (Eric J. G.)
- Sijbrands E.J.G. (Eric)
- Silander K. (Kaisa)
- Silander K. (Kaisa)
- Silveira A. (Angela)
- Sim X. (Xueling)
- Sim X. (Xueling)
- Simpson L. (Laila)
- Singleton A. (Andrew)
- Sinisalo J. (Juha)
- Siscovick D.S. (David)
- Siscovick D.S. (David)
- Sladek R. (Rob)
- Sladek R. (Rob)
- Slagboom P.E. (Eline)
- Small K.S. (Kerrin)
- Smith A.V. (Albert Vernon)
- Smith A.V. (Albert)
- Smith A.V. (Davey)
- Smith A.V. (Davey)
- Smith G.D. (George Davey)
- Smith J.D. (Joshua D.)
- Smith N.L. (Nicholas)
- Song K. (Kijoung)
- Soranzo N. (Nicole)
- Soranzo N. (Nicole)
- Sovio U. (Ulla)
- SparsĂž T. (Thomas)
- SparsĂž T. (Thomas)
- Spector T.D. (Tim D.)
- Spector T.D. (Timothy D.)
- Spector T.D. (Timothy)
- Spranger J. (Joachim)
- St Pourcain B. (Beate)
- Stefansson K. (Kari)
- Stefansson K. (Kari)
- Stein L.D. (Lincoln)
- Steinthorsdottir V. (Valgerdur)
- Steinthorsdottir V. (Valgerdur)
- Strachan D.P. (David)
- Strassburger K. (Klaus)
- Stringham H.M. (Heather M.)
- Stringham H.M. (Heather M.)
- Stringham H.M. (Heather)
- Stumvoll M. (Michael)
- Stylianou I.M. (Ioannis M.)
- Stylianou I.M. (Ioannis)
- Sun Q. (Qi)
- Surakka I. (Ida)
- Swift A.J. (Amy)
- Swift A.J. (Amy)
- Syddall H. (Holly)
- SyvÀnen A.C.
- Tai E.-S. (E-Shyong)
- Tai E.S. (Shyong)
- Tall A.R. (Alan R.)
- Tanaka T. (Toshiko)
- Taylor H.A. (Herman A.)
- Taylor H.A. (Herman)
- Teslovich T.M. (Tanya M.)
- Teslovich T.M. (Tanya M.)
- Thompson J.R. (John)
- Thompson J.R. (John)
- Thorand B. (Barbara)
- Thorand B. (Barbara)
- Thorleifsson G. (Gudmar)
- Thorleifsson G. (Gudmar)
- Thorleifsson G. (Gudmar)
- Thorsteinsdottir U. (Unnur)
- Thorsteinsdottir U. (Unnur)
- Thorsteinsdottir U. (Unnur)
- Thorsteinsdottir U. (Unnur)
- Tichet J. (Jean)
- Tichet J. (Jean)
- Timpson N.J. (Nicholas J.)
- Timpson N.J. (Nicholas)
- Tracy R.P. (Russell)
- Tuomi T. (Tiinamaija)
- Tuomi T. (Tiinamaija)
- Tuomilehto J. (Jaakko)
- Tuomilehto J. (Jaakko)
- Tuomilehto J. (Jaakko)
- Tönjes A. (Anke)
- Uda M. (Manuela)
- Uda M. (Manuela)
- Uh H.-W. (Hae-Won)
- Uitterlinden A. (Andre)
- Uitterlinden A.G. (Andre G.)
- Uitterlinden A.G. (André)
- Valle T.T. (Timo T.)
- van Duijn C. (Cornelia)
- van Duijn C.M. (Cornelia M.)
- van Duijn C.M. (Cornelia M.)
- van Hoek M. (Mandy)
- Varma D. (Dhiraj)
- Viikari J. (Jorma)
- Visvikis-Siest S. (Sophie)
- Vitart V. (Veronique)
- Vitart V. (Veronique)
- Vliet-Ostaptchouk J.V. (Jana) van
- Vogelzangs N. (Nicole)
- Voight B.F. (Benjamin F.)
- Voight B.F. (Benjamin F.)
- Voight B.F. (Benjamin)
- Vollenweider P. (Peter)
- Vollenweider P. (Peter)
- Vollenweider P. (Peter)
- Waeber G. (GĂ©rard)
- Waeber G. (GĂ©rard)
- Wagner P.J. (Peter)
- Walker M. (Mark)
- Walley A. (Andrew)
- Walters G. (GBragi)
- Walters G.B. (Bragi)
- Ward K.L. (Kim L.)
- Wareham N.J. (Nick J.)
- Wareham N.J. (Nick)
- Wareham N.J. (Nick)
- Watanabe R.M. (Richard M.)
- Watanabe R.M. (Richard)
- Waterworth D. (Dawn)
- Waterworth D. (Dawn)
- Waterworth D.M. (Dawn)
- Watkins H. (Hugh)
- Weedon M.N. (Michael)
- Weedon M.N. (Michael)
- Welch R.P. (Ryan)
- Wheeler E. (Eleanor)
- Whitfield J. (John)
- Wichmann H.-E. (H.-Erich)
- Wichmann H.E. (H. Erich)
- Wichmann H.E. (Heinz Erich)
- Wichmann H.E. (Heinz Erich)
- Wijmenga C. (Cisca)
- Wild S.H. (Sarah)
- Willems van Dijk J.A.P. (Ko)
- Willems S.M. (Sara)
- Willems-vanDijk K. (Ko)
- Willemsen G.
- Willemsen G.A.H.M. (Gonneke)
- Willer C.J. (Cristen J.)
- Willer C.J. (Cristen)
- Williams G.H. (Gordon)
- Wilson J.F. (James F.)
- Wilson J.F. (James)
- Wilson J.G. (James G.)
- Winkler T.W. (Thomas W.)
- Witteman J. (Jacqueline)
- Witteman J.C.M. (Jacqueline C. M.)
- Witteman J.C.M. (Jacqueline)
- Witteman J.C.M. (Jaqueline C. M.)
- Wong T.Y. (Tien Y.)
- Wood A.R. (Andrew)
- Wright A.F. (Alan)
- Wright A.F. (Alan)
- Wu G. (Guanming)
- Wu Y. (Ying)
- Yarnell J.W.G. (John W.)
- Yuan X. (Xin)
- Zabena C. (Carina)
- Zee R.Y.L. (Robert)
- Zeggini E. (Eleftheria)
- Zeggini E. (Eleftheria)
- Zelenika D. (Diana)
- Zethelius B. (Björn)
- Zhai G. (Guangju)
- Zhang W. (Weihua)
- Zhao J.H. (Jing Hua)
- Zhao J.H. (Jing Hua)
- Zhao J.H. (Jing Hua)
- Ziegler A. (Andreas)
- Zillikens M.C. (Carola)
- Zwart J-A. (John-Anker)
- Ădonnell C.J. (Christopher)
- Publication venue
- Publication date
- 01/01/2012
- Field of study
Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5Ă10â8- 1.2 Ă10â43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3Ă10â4). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3Ă10â3, n = 22,044), increased triglycerides (p = 2.6Ă10â14, n = 93,440), increased waist-to-hip ratio (p = 1.8Ă10â5, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4Ă10â3, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL- cholesterol concentrations (p = 4.5Ă10â13, n = 96,748) and decreased BMI (p = 1.4Ă10â4, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance
Genome-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)
- Anand S.S. (Sonia)
- Andersen K.K. (Karl)
- Ardissino D. (Diego)
- Ardlie K.G. (Kristin)
- Armitage J. (Jane)
- Arnold A.M. (Alice)
- Aspelund T. (Thor)
- Assimes T.L. (Themistocles)
- Assmann G. (Gerd)
- Aulchenko Y.S. (Yurii)
- Azhar M. (Muhammad)
- Balkau B. (Beverley)
- Ball S.G. (Stephen G.)
- Barbalic M. (maja)
- Barker A.M. (Adam)
- Barlassina C. (Christina)
- Barlera S. (Simona)
- Barnes D. (Daniel)
- Barnes T.A. (Timothy)
- Barrett A. (Angela)
- Barroso I.E. (InĂȘs)
- Bataille V. (Veronique)
- Becker D.M. (Diane)
- Becker L.C. (Lewis)
- Beckmann J.S. (Jacques)
- Beckmann J.S. (Jacques)
- Beilby J.P. (John)
- Bell J.T. (Jordana)
- Ben-Shlomo Y.
- Ben-Shlomo Y. (Yoav)
- Bennett A.J. (Amanda)
- Berger K. (Klaus)
- Bergman R.N. (Richard N.)
- Bergmann S.M. (Sven)
- Berndt S.I. (Sonja)
- Biebermann H. (Heike)
- Bis J.C. (Joshua)
- Blagieva R. (Roza)
- Blakemore A.I.F. (Alexandra)
- Blankenberg S. (Stefan)
- Boehm B.O. (Bernhard)
- Boehm B.O. (Bernhard)
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- Boeing H. (Heiner)
- Boeing H. (Heiner)
- Boekholdt S.M. (Matthijs)
- Boerwinkle E.A. (Eric)
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- Bonnycastle L.L. (Lori)
- Boomsma D.I. (Dorret)
- Borecki I.B. (Ingrid)
- Bornstein S.R. (Stefan R.)
- Bornstein S.R. (Stefan)
- Boström K.B. (Kristina Bengtsson)
- Bouatia-Naji N. (Nabila)
- Bowman L.
- Braund P.S. (Peter)
- Bravenboer B. (Bert)
- Buchanan T.A. (Thomas)
- Bumpstead S. (Suzannah)
- Burnett M.S.
- Burtt N.P. (Noël)
- Busonero F.
- Buysschaert I. (Ian)
- Cambien F. (François)
- Campbell H. (Harry)
- Cappuccio F.P. (Francesco P.)
- Cappuccio F.P. (Francesco)
- Carlquist J.F. (John)
- Cauchi S. (Stephane)
- Caulfield M. (Mark)
- Cavalcanti-Proença C. (Christine)
- Chambers J.C. (John C.)
- Chambers J.C. (John)
- Chanock S.J. (Stephen)
- Charpentier G. (Guillaume)
- Chasman D.I. (Daniel)
- Chatterjee N. (Nilanjan)
- Chen C.-M. (Chih-Mei)
- Chen H. (Han)
- Chen L. (Li)
- Chines P.S. (Peter)
- Cichon S. (Sven)
- Clarke R.
- Clarke R. (Robert)
- Codd V. (Veryan)
- Coin L. (Lachlan)
- Coin L. (Lachlan)
- Collins F.S. (Francis S.)
- Collins F.S. (Francis)
- Collins F.S. (Francis)
- Connell J. (John)
- Cooper C. (Charles)
- Cooper C.C. (Cyrus C.)
- Cooper M.N. (Matthew N.)
- Cooper M.N. (Matthew)
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- Couper D.J. (David)
- Crawford G. (Gabe)
- Cupples L.A. (Adrienne)
- Daly M.J. (Mark)
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- Danesh J. (John)
- Davies R.W. (Robert)
- Day I.N.M. (Ian N.M.)
- Day I.N.M. (Ian)
- Dedoussis G.V. (George)
- Dedoussis G.V. (George)
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- Dehghan A. (Abbas)
- Deloukas P. (Panagiotis)
- Demissie S. (Serkalem)
- Den Heijer M. (Martin)
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- Dermitzakis E.T. (Emmanouil T.)
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- Dupuis J. (Josée)
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- Hayes R.B. (Richard)
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- Heinrich J. (Joachim)
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- Johnson P.R.V. (Paul R.V.)
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- Kaplan L. (Lee)
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- Tammesoo M.L.
- Taneera J. (Jalal)
- Tang W. (W.)
- Tardif J.-C. (Jean-Claude)
- Tennstedt S. (Stephanie)
- Teslovich T.M. (Tanya M.)
- Thiering E. (Eelisabeth)
- Thiering E. (Elisabeth)
- Thompson J.R. (John)
- Thomson B. (Brian)
- Thorand B. (Barbara)
- Thorand B. (Barbara)
- Thorgeirsson G. (Gudmundur)
- Thorleifsson G. (Gudmar)
- Thorsteinsdottir U. (Unnur)
- Tichet J. (Jean)
- Timpson N.J. (Nicholas)
- Tognoni G.
- Tomaszewski M. (Maciej)
- Travers M.E. (Mary E.)
- Travers M.E. (Mary)
- Tuomi T. (Tiinamaija)
- Tuomilehto J. (Jaakko)
- Turrini F. (Fabiola)
- Tyrer J.P. (Jonathan)
- Tönjes A. (Anke)
- Uda M. (Manuela)
- Uitterlinden A.G. (André)
- Valle T.T. (Timo T.)
- Van Dam R.M. (Rob M.)
- van't Hooft F. (Ferdinand)
- Van't Hooft F. (Ferdinand)
- Vatin V. (Vincent)
- Vedantam S. (Sailaja)
- Visscher P.M. (Peter M.)
- Visscher P.M. (Peter)
- Vitart V. (Veronique)
- Vliet-Ostaptchouk J.V. (Jana) van
- Voight B.F. (Benjamin)
- Wabitsch M. (Martin)
- Waeber G. (GĂ©rard)
- Waite L. (Lindsay)
- Walker M. (Mark)
- Wallaschofski H. (Henri)
- Walters G.B. (Bragi)
- Wareham N.J. (Nicholas J.)
- Wareham N.J. (Nick)
- Watanabe R.M. (Richard)
- Watkins H. (Hugh)
- Weedon M.N. (Michael)
- Weedon M.N. (Michael)
- Welch R. (Ryan)
- Welch R.P. (Ryan)
- Wells G.A. (George)
- Weyant R.J. (Robert)
- Wheeler E. (Eleanor)
- White C.C. (Charles)
- Wichmann H.-E. (H-Erich)
- Wichmann H.E. (Heinz Erich)
- Widen E. (Elisabeth)
- Wiegand S. (Susanna)
- Wijmenga C. (Cisca)
- Wiklund F. (Fredrik)
- Wild P.S. (Philipp)
- Wild S.H. (Sarah)
- Wilk A. (Alicja)
- Willemsen G.A.H.M. (Gonneke)
- Willenborg C. (Christina)
- Willer C.J. (Cristen)
- Wilson J.F. (James F.)
- 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)
- Ăhrvik J. (John)
- Ăstenson C.-G. (Claes-Göran)
- Publication venue
- Publication date
- 01/10/2011
- Field of study
OBJECTIVE - 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 Ă 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 Ă 10-5), and lower risk of T2D (odds ratio 0.88; P = 7.8 Ă 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