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3. Bariatric surgery in a patient with cystic fibrosis and diabetes:A case report

Author

Bruijn, N. R.A., Wagenmakers, M. A.E.M., van Hoek, M., Apers, J. A., van der Eerden, M. M., Özcan, B., Bruijn, N. R.A., Wagenmakers, M. A.E.M., van Hoek, M., Apers, J. A., van der Eerden, M. M., and Özcan, B.

Abstract

Cystic fibrosis (CF) is incurable and chronic, causing severe multisystemic damage and long-term complications. The most prominent extrapulmonary long-term complication is CF-related diabetes, which is the most reported form of diabetes in individuals with cystic fibrosis. Here we present the first case of an individual with cystic fibrosis who developed type 2 diabetes due to obesity rather than CF-related diabetes. The type 2 diabetes went into remission due to extreme weight loss after gastric bypass surgery. To our knowledge, this case is also the first report describing the effect of bariatric surgery in a patient with CF. This case demonstrates that patients with CF may present with type 2 diabetes instead of CF-related diabetes. Differential diagnosis of these two types of diabetes is essential for optimal treatment and quality of life.

Published
2023

5. Perinatal outcome after selective fetal reduction in monochorionic twin pregnancies: A comparison of techniques over a 20‐year period.

Author

van Hoek, M. J. C., van Klink, J. M. M., Verweij, E. J. T., Middeldorp, J. M., Haak, M. C., Lopriore, E., and Slaghekke, F.

Abstract

Objective: To assess the perinatal outcome after fetal reduction in complicated monochorionic (MC) twin pregnancies by comparing different techniques. Methods: A retrospective cohort study at a national referral center comparing data between four techniques: interstitial laser coagulation, radiofrequency ablation (RFA), fetoscopic laser coagulation (FLC) and bipolar cord coagulation (BCC). The primary outcome was the mortality of the co‐twins. Secondary outcomes were preterm pre‐labor rupture of membranes (PPROM), gestational age at delivery and neonatal morbidity. Results: 259 MC twin pregnancies underwent selective fetal reduction: 29 IL, 64 RFA, 85 FLC and 81 BCC. The perinatal mortality rate was 29% and fetal demise of the co‐twins occurred in 19%. The lowest mortality rate was seen after BCC (17%, p = 0.012). PPROM occurred in 18% patients without significant differences between techniques. The mean gestational age at delivery in liveborn children was 35 weeks and did not differ between techniques. Severe cerebral injury and neonatal morbidity were reported in 4% and 14%, respectively, without significant differences between techniques. Conclusions: Selective fetal reductions in MC twins are precarious procedures with an increased risk of perinatal mortality of the co‐twins. Our results show the lowest mortality rates after BCC. However, high PPROM rates were seen irrespective of the technique. Key points: What is already known about this topic? Selective fetal reductions are precarious procedures and can be carried out using different techniques.It has been suggested that radiofrequency ablation has superior outcomes because of the smaller diameter of the instrument, resulting in fewer complications.To date, there is no international consensus on which technique for which the indication is ideal and has the best perinatal outcome. What does this study add? Selective fetal reductions in monochorionic twins have the lowest mortality rate of the co‐twin after bipolar cord coagulation and the highest after interstitial laser coagulation.High preterm pre‐labor rupture of membranes rates before 32 weeks gestational age was seen irrespective of the technique.The selection of the most ideal technique should be made per pregnancy, considering gestational age, indication and feasibility. [ABSTRACT FROM AUTHOR]

Published
2023
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12. Breakfast partly restores the anti-inflammatory function of high-density lipoproteins from patients with type 2 diabetes mellitus

Author

Lemmers, R. F.H., Martens, N. E.M.A., Maas, A. H., van Vark-van der Zee, L. C., Leijten, F. P.J., Groot-van Ruijven, C. M., van Hoek, M., Lieverse, A. G., Sijbrands, E. J.G., Haak, H. R., Leenen, P. J.M., Verhoeven, A. J.M., Dik, W. A., Mulder, M. T., Lemmers, R. F.H., Martens, N. E.M.A., Maas, A. H., van Vark-van der Zee, L. C., Leijten, F. P.J., Groot-van Ruijven, C. M., van Hoek, M., Lieverse, A. G., Sijbrands, E. J.G., Haak, H. R., Leenen, P. J.M., Verhoeven, A. J.M., Dik, W. A., and Mulder, M. T.

Published
2021

15. Automated quantification of river morphodynamics from satellite imagery for large multithreaded rivers

Author

Rawee, J., Huthoff, F., Augustijn, D.C.M., van Hoek, M., Uijttewaal, Wim, Franca, Mario J., Valero, Daniel, Chavarrias, Victor, Ylla Arbos, Claudia, Schielen, Ralph, Crosato, Alessandra, and Marine and Fluvial Systems

Abstract

In recent years, various studies have appeared on (automated) processing of river morphodynamics from satellite images. A key challenge in such approaches is to use appropriate and consistent methods to quantify eroded and deposited areas and channel migration rates. This is particularly important in highly dynamic multi-threaded rivers, where apparent bank lines can move significantly with changing water levels. To assure a consistent treatment of bank lines we use a methodology where channels are identified by detecting the vegetation boundary. We apply this methodology to a 250 km reach of the Ayeyarwady river (Myanmar) and extract metrics for eroded and deposited areas and channel migration. These morphological metrics are compared to hydrologic conditions, and significant correlations were found. It shows that the proposed method may help to classify and better understand river dynamics rivers of large multithreaded rivers.

Published
2020

27. Parental origin of sequence variants associated with complex diseases

Author

Voight, B.F., Raychaudhuri, S., Purcell, S., McCarroll, S.A., Segrè, A.V., Ardlie, K., Burtt, N.P., Crawford, G., Elliott, A.L., Green, T., Guiducci, C., Saxena, R., Daly, M.J., Florez, J.C., Altshuler, D., Meigs, J.B., Scott, L.J., Welch, R.P., Willer, C.J., Ganser, M., Jackson, A.U., Stringham, H.M., Abecasis, G.R., Boehnke, M., Steinthorsdottir, V., Thorleifsson, G., Kong, A., Walters, G.B., Thorsteinsdottir, U., Stefansson, K., Dina, C., Proença, C., Cauchi, S., Froguel, P., Zeggini, E., Bumpstead, S., Payne, F., Smith, N., Barroso, I., Ferreira, T., Elliott, K.S., Lindgren, C.M., Prokopenko, I., Rayner, N.W., Robertson, N.R., Morris, A.P., McCarthy, M.I., Huth, C., Grallert, H., Gieger, C., Klopp, N., Meitinger, T., Petersen, A.-K., Thorand, B., Wichmann, H.-E., Illig, T., Aulchenko, Y.S., Amin, N., Witteman, J., Hofman, A., Van Duijn, C.M., McCulloch, L.J., Bennett, A.J., Groves, C.J., Hassanali, N., Owen, K.R., Gloyn, A.L., Wu, G., Stein, L.D., Langenberg, C., Griffin, S., Wareham, N.J., Hoffmann, O.M., Hide, W.A., Dupuis, J., Qi, L., Kraft, P., Sun, Q., Hunter, D., Hu, F.B., Cornelis, M., VanDam, R., Van Hoek, M., Van Herpt, T., Sijbrands, E., Uitterlinden, A., Navarro, P., Balkau, B., Benediktsson, R., Sigurdsson, G., Blagieva, R., Boehm, B.O., Boerwinkle, E., Bonnycastle, L.L., Chines, P.S., Erdos, M.R., Morken, M.A., Narisu, N., Swift, A.J., Boström, K.B., Bravenboer, B., Charpentier, G., Couper, D.J., Doney, A.S.F., Morris, A.D., Palmer, C.N.A., Fox, C.S., Franklin, C.S., Rudan, I., Grarup, N., Hadjadj, S., Thomas Sparsø, [No Value], Campbell, H., Wilson, J.F., Hansen, T., Pedersen, O., Herder, C., Roden, M., Isomaa, B., Tuomi, T., Johnson, P.R.V., Jørgensen, T., Kao, W.H.L., Kuusisto, J., Laakso, M., Lauritzen, T., Li, M., Lieverse, A., Lyssenko, V., Nilsson, P., Groop, L., Marre, M., Midthjell, K., Platou, C., Hveem, K., Perry, J.R.B., Shields, B.M., Weedon, M.N., Frayling, T.M., Hattersley, A.T., Rathmann, W., Strassburger, K., Rocheleau, G., Sladek, R., Sampson, M.J., Shrader, P., Tichet, J., Bergman, R.N., Collins, F.S., Gyllensten, U., Hitman, G.A., Mohlke, K.L., Pramstaller, P.P., Tuomilehto, J., Walker, M., Watanabe, R.M., Pankow, J.S., and deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland. kong@decode.is

Subjects
Male, CCCTC-Binding Factor, Iceland, Mothers, Breast Neoplasms, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Fathers, Genomic Imprinting, 03 medical and health sciences, 0302 clinical medicine, Polymorphism (computer science), Humans, SNP, Genetic Predisposition to Disease, Allele, Alleles, 030304 developmental biology, Genetics, 0303 health sciences, Binding Sites, Multidisciplinary, Genome, Human, Chromosomes, Human, Pair 11, Haplotype, DNA Methylation, Pedigree, Repressor Proteins, Diabetes Mellitus, Type 2, Haplotypes, Carcinoma, Basal Cell, DNA methylation, Female, Human genome, Genomic imprinting, Chromosomes, Human, Pair 7, 030217 neurology & neurosurgery
Abstract

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site. info:eu-repo/grantAgreement/EC/FP7/218071

Published
2009
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28. The Lin28/let-7 axis regulates glucose metabolism

Author

Zhu H, Shyh Chang N, Segrè AV, Shinoda G, Shah SP, Einhorn WS, Takeuchi A, Engreitz JM, Hagan JP, Kharas MG, Urbach A, Thornton JE, Triboulet R, Gregory RI, DIAGRAM Consortium, MAGIC Investigators, Altshuler D, Daley G.Q. Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, McCulloch LJ, Ferreira T, Grallert H, Amin N, Wu G, Willer CJ, Raychaudhuri S, McCarroll SA, Langenberg C, Hofmann OM, Dupuis J, Qi L, van Hoek M, Navarro P, Ardlie K, Balkau B, Benediktsson R, Bennett AJ, Blagieva R, Boerwinkle E, Bonnycastle LL, Boström KB, Bravenboer B, Bumpstead S, Burtt NP, Charpentier G, Chines PS, Cornelis M, Couper DJ, Crawford G, Doney AS, Elliott KS, Elliott AL, Erdos MR, Fox CS, Franklin CS, Ganser M, Gieger C, Grarup N, Green T, Griffin S, Groves CJ, Guiducci C, Hadjadj S, Hassanali N, Herder C, Isomaa B, Jackson AU, Johnson PR, Jørgensen T, Kao WH, Klopp N, Kong A, Kraft P, Kuusisto J, Lauritzen T, Li M, Lieverse A, Lindgren CM, Lyssenko V, Marre M, Meitinger T, Midthjell K, Morken MA, Narisu N, Nilsson P, Owen KR, Payne F, Perry JR, Petersen AK, Platou C, Proença C, Prokopenko I, Rathmann W, Rayner NW, Robertson NR, Rocheleau G, Roden M, Sampson MJ, Saxena R, Shields BM, Shrader P, Sigurdsson G, Sparsø T, Strassburger K, Stringham HM, Sun Q, Swift AJ, Thorand B, Tichet J, Tuomi T, van Dam RM, van Haeften TW, van Herpt T, van Vliet Ostaptchouk JV, Walters GB, Weedon MN, Wijmenga C, Witteman J, Bergman RN, Cauchi S, Collins FS, Gloyn AL, Gyllensten U, Hansen T, Hide WA, Hitman GA, Hofman A, Hunter DJ, Hveem K, Laakso M, Mohlke KL, Morris AD, Palmer CN, Pramstaller PP, Rudan I, Sijbrands E, Stein LD, Tuomilehto J, Uitterlinden A, Walker M, Wareham NJ, Watanabe RM, Abecasis GR, Boehm BO, Campbell H, Daly MJ, Hattersley AT, Hu FB, Meigs JB, Pankow JS, Pedersen O, Wichmann HE, Barroso I, Florez JC, Frayling TM, Groop L, Sladek R, Thorsteinsdottir U, Wilson JF, Illig T, Froguel P, van Duijn CM, Stefansson K, Boehnke M, McCarthy MI, Soranzo N, Wheeler E, Glazer NL, Bouatia Naji N, Mägi R, Randall J, Johnson T, Elliott P, Rybin D, Henneman P, Dehghan A, Hottenga JJ, Song K, Goel A, Egan JM, Lajunen T, Doney A, Voight BF, Kanoni S, Cavalcanti Proença C, Kumari M, Timpson NJ, Zabena C, Ingelsson E, An P, O'Connell J, Luan J, Elliott A, Roccasecca RM, Pattou F, Sethupathy P, Ariyurek Y, Barter P, Beilby JP, Ben Shlomo Y, Bergmann S, Bochud M, Bonnefond A, Borch Johnsen K, Böttcher Y, Brunner E, Bumpstead SJ, Chen YD, Chines P, Clarke R, Coin LJ, Cooper MN, Crisponi L, Day IN, de Geus EJ, Delplanque J, Fedson AC, Fischer Rosinsky A, Forouhi NG, Frants R, Franzosi MG, Galan P, Goodarzi MO, Graessler J, Grundy S, Gwilliam R, Hallmans G, Hammond N, Han X, Hartikainen AL, Hayward C, Heath SC, Hercberg S, Hicks AA, Hillman DR, Hingorani AD, Hui J, Hung J, Jula A, Kaakinen M, Kaprio J, Kesaniemi YA, Kivimaki M, Knight B, Koskinen S, Kovacs P, Kyvik KO, Lathrop GM, Lawlor DA, Le Bacquer O, Lecoeur C, Li Y, Mahley R, Mangino M, Manning AK, Martínez Larrad MT, McAteer JB, McPherson R, Meisinger C, Melzer D, Meyre D, Mitchell BD, Mukherjee S, Naitza S, Neville MJ, Oostra BA, Orrù M, Pakyz R, Pattaro C, Pearson D, Peden JF, Pedersen NL, Perola M, Pfeiffer AF, Pichler I, Polasek O, Posthuma D, Potter SC, Pouta A, Province MA, Psaty BM, Rice K, Ripatti S, Rivadeneira F, Rolandsson O, Sandbaek A, Sandhu M, Sanna S, Sayer AA, Scheet P, Seedorf U, Sharp SJ, Shields B, Sigurðsson G, Sijbrands EJ, Silveira A, Simpson L, Singleton A, Smith NL, Sovio U, Swift A, Syddall H, Syvänen AC, Tanaka T, Tönjes A, Uitterlinden AG, van Dijk KW, Varma D, Visvikis Siest S, Vitart V, Vogelzangs N, Waeber G, Wagner PJ, Walley A, Ward KL, Watkins H, Wild SH, Willemsen G, Witteman JC, Yarnell JW, Zelenika D, Zethelius B, Zhai G, Zhao JH, Zillikens MC, Borecki IB, Loos RJ, Meneton P, Magnusson PK, Nathan DM, Williams GH, Silander K, Salomaa V, Smith GD, Bornstein SR, Schwarz P, Spranger J, Karpe F, Shuldiner AR, Cooper C, Dedoussis GV, Serrano Ríos M, Lind L, Palmer LJ, Franks PW, Ebrahim S, Marmot M, Wright AF, Stumvoll M, Hamsten A, Buchanan TA, Valle TT, Rotter JI, Siscovick DS, Penninx BW, Boomsma DI, Deloukas P, Spector TD, Ferrucci L, Cao A, Scuteri A, Schlessinger D, Uda M, Ruokonen A, Jarvelin MR, Waterworth DM, Vollenweider P, Peltonen L, Mooser V, Barroso I., PAOLISSO, Giuseppe, Zhu, H, Shyh Chang, N, Segrè, Av, Shinoda, G, Shah, Sp, Einhorn, W, Takeuchi, A, Engreitz, Jm, Hagan, Jp, Kharas, Mg, Urbach, A, Thornton, Je, Triboulet, R, Gregory, Ri, Diagram, Consortium, Magic, Investigator, Altshuler, D, Voight BF, Daley G. Q., Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Y, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Langenberg, C, Hofmann, Om, Dupuis, J, Qi, L, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Boström, Kb, Bravenboer, B, Bumpstead, S, Burtt, Np, Charpentier, G, Chines, P, Cornelis, M, Couper, Dj, Crawford, G, Doney, A, Elliott, K, Elliott, Al, Erdos, Mr, Fox, C, Franklin, C, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, Au, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Narisu, N, Nilsson, P, Owen, Kr, Payne, F, Perry, Jr, Petersen, Ak, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, Rayner, Nw, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Swift, Aj, Thorand, B, Tichet, J, Tuomi, T, van Dam, Rm, van Haeften, Tw, van Herpt, T, van Vliet Ostaptchouk, Jv, Walters, Gb, Weedon, Mn, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Collins, F, Gloyn, Al, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Laakso, M, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Walker, M, Wareham, Nj, Watanabe, Rm, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Meigs, Jb, Pankow, J, Pedersen, O, Wichmann, He, Barroso, I, Florez, Jc, Frayling, Tm, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Froguel, P, van Duijn, Cm, Stefansson, K, Boehnke, M, Mccarthy, Mi, Soranzo, N, Wheeler, E, Glazer, Nl, Bouatia Naji, N, Mägi, R, Randall, J, Johnson, T, Elliott, P, Rybin, D, Henneman, P, Dehghan, A, Hottenga, Jj, Song, K, Goel, A, Egan, Jm, Lajunen, T, Voight, Bf, Kanoni, S, Cavalcanti Proença, C, Kumari, M, Timpson, Nj, Zabena, C, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, Roccasecca, Rm, Pattou, F, Sethupathy, P, Ariyurek, Y, Barter, P, Beilby, Jp, Ben Shlomo, Y, Bergmann, S, Bochud, M, Bonnefond, A, Borch Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, Sj, Chen, Yd, Clarke, R, Coin, Lj, Cooper, Mn, Crisponi, L, Day, In, de Geus, Ej, Delplanque, J, Fedson, Ac, Fischer Rosinsky, A, Forouhi, Ng, Frants, R, Franzosi, Mg, Galan, P, Goodarzi, Mo, Graessler, J, Grundy, S, Gwilliam, R, Hallmans, G, Hammond, N, Han, X, Hartikainen, Al, Hayward, C, Heath, Sc, Hercberg, S, Hicks, Aa, Hillman, Dr, Hingorani, Ad, Hui, J, Hung, J, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, Ya, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, Ko, Lathrop, Gm, Lawlor, Da, Le Bacquer, O, Lecoeur, C, Li, Y, Mahley, R, Mangino, M, Manning, Ak, Martínez Larrad, Mt, Mcateer, Jb, Mcpherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, Bd, Mukherjee, S, Naitza, S, Neville, Mj, Oostra, Ba, Orrù, M, Pakyz, R, Paolisso, Giuseppe, Pattaro, C, Pearson, D, Peden, Jf, Pedersen, Nl, Perola, M, Pfeiffer, Af, Pichler, I, Polasek, O, Posthuma, D, Potter, Sc, Pouta, A, Province, Ma, Psaty, Bm, Rice, K, Ripatti, S, Rivadeneira, F, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, Aa, Scheet, P, Seedorf, U, Sharp, Sj, Shields, B, Sigurðsson, G, Sijbrands, Ej, Silveira, A, Simpson, L, Singleton, A, Smith, Nl, Sovio, U, Swift, A, Syddall, H, Syvänen, Ac, Tanaka, T, Tönjes, A, Uitterlinden, Ag, van Dijk, Kw, Varma, D, Visvikis Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, Pj, Walley, A, Ward, Kl, Watkins, H, Wild, Sh, Willemsen, G, Witteman, Jc, Yarnell, Jw, Zelenika, D, Zethelius, B, Zhai, G, Zhao, Jh, Zillikens, Mc, Borecki, Ib, Loos, Rj, Meneton, P, Magnusson, Pk, Nathan, Dm, Williams, Gh, Silander, K, Salomaa, V, Smith, Gd, Bornstein, Sr, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, Ar, Cooper, C, Dedoussis, Gv, Serrano Ríos, M, Lind, L, Palmer, Lj, Franks, Pw, Ebrahim, S, Marmot, M, Wright, Af, Stumvoll, M, Hamsten, A, Buchanan, Ta, Valle, Tt, Rotter, Ji, Siscovick, D, Penninx, Bw, Boomsma, Di, Deloukas, P, Spector, Td, Ferrucci, L, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, Mr, Waterworth, Dm, Vollenweider, P, Peltonen, L, Mooser, V, and Barroso, I.

Published
2011

30. Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis

Author

Stahl, E. A., Wegmann, D., Trynka, G., Gutierrez Achury, J., Do, R., Voight, B. F., Kraft, P., Chen, R., Kallberg, H. J., F. A. S., Replication, D. G., Consortium, M. a., Genetics, M. I., Kathiresan, S., Wijmenga, C., Gregersen, P. K., Alfredsson, L., Siminovitch, K. A., Worthington, J., P. I. W., Raychaudhuri, S., Plenge, R. M., Voight, Bf, Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Ys, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Langenberg, C, Hofmann, Om, Dupuis, J, Qi, L, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Boström, Kb, Bravenboer, B, Bumpstead, S, Burtt, Np, Charpentier, G, Chines, Ps, Cornelis, M, Couper, Dj, Crawford, G, Doney, As, Elliott, Ks, Elliott, Al, Erdos, Mr, Fox, Cs, Franklin, Cs, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, Au, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Narisu, N, Nilsson, P, Owen, Kr, Payne, F, Perry, Jr, Petersen, Ak, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, Rayner, Nw, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Swift, Aj, Thorand, B, Tichet, J, Tuomi, T, van Dam RM, van Haeften TW, van Herpt, T, van Vliet Ostaptchouk JV, Walters, Gb, Weedon, Mn, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Collins, Fs, Gloyn, Al, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Laakso, M, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Walker, M, Wareham, Nj, Watanabe, Rm, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Meigs, Jb, Pankow, Js, Pedersen, O, Wichmann, He, Barroso, I, Florez, Jc, Frayling, Tm, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Froguel, P, van Duijn CM, Stefansson, K, Altshuler, D, Boehnke, M, Mccarthy, Mi, Kathiresan, S, Williams, G, Nathan, Dm, Macrae, Ca, O'Donnell, Cj, Ardissino, D, Merlini, Pa, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Ferrario, M, Fetiveau, R, Marziliano, N, Casari, G, Galli, M, Ribichini, Flavio Luciano, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Mannucci, Pm, Schwartz, Sm, Siscovick, Ds, Yee, J, Friedlander, Y, Elosua, R, Marrugat, J, Lucas, G, Subirana, I, Sala, J, Ramos, R, Salomaa, V, Havulinna, As, Peltonen, L, Melander, O, Berglund, G, Hirschhorn, Jn, Asselta, R, Duga, S, Spreafico, M, Musunuru, K, Purcell, S, Surti, A, Gianniny, L, Mirel, D, Parkin, M, Burtt, N, Gabriel, Sb, Stahl, Ea, Wegmann, D, Trynka, G, Gutierrez achury, J, Do, R, Voight, Bf, Kraft, P, Che, R, Kallberg, H, Kurreeman, F, Diabetes Genetics Replication And Meta analysis Consortium: Myocardial Infarction Genetics, Consortium, Casari, GIORGIO NEVIO, Kathiresan, S, Wijmenga, C, Gregersen, Pk, Alfredsson, L, Siminovitch, Ka, Worthington, J, De Bakker, Pi, Raychaudhuri, S, Plenge, Rm, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Subjects
Multifactorial Inheritance, SUSCEPTIBILITY LOCI, GENETIC SUSCEPTIBILITY, Genome-wide association study, Single-nucleotide polymorphism, Disease, HEART-DISEASE, Biology, VARIANTS, Polymorphism, Single Nucleotide, Article, Arthritis, Rheumatoid, COMMON SNPS, Missing heritability problem, MISSING HERITABILITY, Rheumatoid, Genetic model, Genetic predisposition, Diabetes Mellitus, Humans, genetics, Genetic Predisposition to Disease, Human height, Polymorphism, GENOME-WIDE ASSOCIATION, Arthritis, genetics, Bayes Theorem, Cardiovascular Diseases, genetics, Case-Control Studies, Celiac Disease, genetics, Diabetes Mellitus, Type 2, genetics, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Genetics, CELIAC-DISEASE, Bayes Theorem, RISK LOCI, Genetic architecture, Celiac Disease, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Genetic Loci, Case-Control Studies, HUMAN HEIGHT, Genome-Wide Association Study
Abstract

The genetic architectures of common, complex diseases are largely uncharacterized. We modeled the genetic architecture underlying genome-wide association study (GWAS) data for rheumatoid arthritis and developed a new method using polygenic risk-score analyses to infer the total liability-scale variance explained by associated GWAS SNPs. Using this method, we estimated that, together, thousands of SNPs from rheumatoid arthritis GWAS explain an additional 20% of disease risk (excluding known associated loci). We further tested this method on datasets for three additional diseases and obtained comparable estimates for celiac disease (43% excluding the major histocompatibility complex), myocardial infarction and coronary artery disease (48%) and type 2 diabetes (49%). Our results are consistent with simulated genetic models in which hundreds of associated loci harbor common causal variants and a smaller number of loci harbor multiple rare causal variants. These analyses suggest that GWAS will continue to be highly productive for the discovery of additional susceptibility loci for common diseases.

Published
2012

31. Management of urban development: Example of the transformation of two Dutch former port areas

Author

Van Hoek, M. and Wigmans, G.

Subjects
organizing capacity, integral vision, city marketing, urban management
Abstract

The more traditional approach of developing cities through government lead town planning has been gradually shifting to a more entrepreneurial approach of strategic management of both public and private initiatives in the urban environment. This approach combines aspects of governance, urban planning, economic development, financial management, social planning and marketing and leads to a more integrated strategic decision making process in which both public and private sector are involved. It is the task of urban management to improve the attractiveness of the city and its relative competitive position by developing and implementing an integrated strategy. This integrated strategy can be seen as a way to realise the objective of strengthening the economical, social and cultural situation of the urban region, which, in its turn, can be reached by taking into account all relevant factors that can influence the development process. The ability to develop and implement an integral urban development vision largely depends on achieving sufficient organising capacity. This organising capacity indicates the organisational possibilities that an urban region possess in order to be able to develop and implement an integral strategy. Organising capacity is the ability to enlist all actors involved, and with their help generate new ideas and develop and implement a policy designed to respond to fundamental developments and create conditions for sustainable economic growth.An important aspect of modern urban management is city marketing. In city marketing attention is focused on the urban functions and their target groups: the potential users of these functions. In urban management, on the contrary, stakeholders have a key position. City marketing and urban management can be seen as the‘ invisible hand’ of market coordination versus the‘ visible hand’ of government regulation. This implies that co-ordination and regulation can be considered as decentralised tasks of urban management.

Published
2011

32. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

Author

Strawbridge, Rj, Dupuis, J, Prokopenko, I, Barker, A, Ahlqvist, E, Rybin, D, Petrie, Jr, Travers, Me, Bouatia Naji, N, Dimas, As, Nica, A, Wheeler, E, Chen, H, Voight, Bf, Taneera, J, Kanoni, S, Peden, Jf, Turrini, F, Gustafsson, S, Zabena, C, Almgren, P, Barker, Dj, Barnes, D, Dennison, Em, Eriksson, Jg, Eriksson, P, Eury, E, Folkersen, L, Fox, Cs, Frayling, Tm, Goel, A, Gu, Hf, Horikoshi, M, Isomaa, B, Jackson, Au, Jameson, Ka, Kajantie, E, Kerr Conte, J, Kuulasmaa, T, Kuusisto, J, Loos, Rj, Luan, J, Makrilakis, K, Manning, Ak, Martínez Larrad MT, Narisu, N, Nastase Mannila, M, Ohrvik, J, Osmond, C, Pascoe, L, Payne, F, Sayer, Aa, Sennblad, B, Silveira, A, Stancáková, A, Stirrups, K, Swift, Aj, Syvänen, Ac, Tuomi, T, van 't Hooft FM, Walker, M, Weedon, Mn, Xie, W, Zethelius, B, Diagram, Consortium, Giant, Consortium, Muther, Consortium, Cardiogram, Consortium, C4d, Consortium, Ongen, H, Mälarstig, A, Hopewell, Jc, Saleheen, D, Chambers, J, Parish, S, Danesh, J, Kooner, J, Ostenson, Cg, Lind, L, Cooper, Cc, Serrano Ríos, M, Ferrannini, E, Forsen, Tj, Clarke, R, Franzosi, Mg, Seedorf, U, Watkins, H, Froguel, P, Johnson, P, Deloukas, P, Collins, Fs, Laakso, M, Dermitzakis, Et, Boehnke, M, Mccarthy, Mi, Wareham, Nj, Groop, L, Pattou, F, Gloyn, Al, Dedoussis, Gv, Lyssenko, V, Meigs, Jb, Barroso, I, Watanabe, Rm, Ingelsson, E, Langenberg, C, Hamsten, A, Voight BF, Florez J. C., Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Ys, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Hofmann, Om, Qi, L, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Bengtsson Boström, K, Bravenboer, B, Bumpstead, S, Burtt, P, Charpentier, G, Chines, Ps, Cornelis, M, Couper, Dj, Crawford, G, Doney, As, Elliott, Ks, Elliott, Al, Erdos, Mr, Franklin, Cs, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Nilsson, P, Owen, Kr, Perry, Jr, Petersen, K, Platou, C, Proença, C, Rathmann, W, William Rayner, N, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Thorand, B, Tichet, J, van Dam RM, van Haeften TW, van Herpt, T, van Vliet JV, Bragi Walters, G, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Pankow, Js, Pedersen, O, Wichmann, E, Florez, Jc, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Stefansson, K, Altshuler, D, Speliotes, Ek, Berndt, Si, Monda, Kl, Allen, Hl, Mägi, R, Randall, Jc, Vedantam, S, Winkler, Tw, Workalemahu, T, Heid, Im, Wood, Ar, Weyant, Rj, Estrada, K, Liang, L, Nemesh, J, Park, Jh, Kilpeläinen, To, Yang, J, Esko, T, Feitosa, Mf, Kutalik, Z, Mangino, M, Scherag, A, Smith, Av, Welch, R, Zhao, Jh, Aben, Kk, Absher, Dm, Dixon, Al, Fisher, E, Glazer, Nl, Goddard, Me, Heard Costa NL, Hoesel, V, Hottenga, Jj, Johansson, Å, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, Mf, Myers, Rh, Peters, Mj, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Timpson, Nj, Tyrer, Jp, van Wingerden, S, White, Cc, Wiklund, F, Barlassina, C, Chasman, Di, Cooper, Mn, Jansson, Jo, Lawrence, Rw, Pellikka, N, Shi, J, Thiering, E, Alavere, H, Alibrandi, Mt, Arnold, Am, Aspelund, T, Atwood, Ld, Balmforth, Aj, Ben Shlomo, Y, Bergmann, S, Biebermann, H, Blakemore, Ai, Boes, T, Bornstein, Sr, Brown, Mj, Buchanan, Ta, Busonero, F, Cappuccio, Fp, Cavalcanti Proença, C, Ida Chen YD, Chen, Cm, Coin, L, Connell, J, Day, In, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Facheris, Mf, Felix, Sb, Fischer Posovszky, P, Folsom, Ar, Friedrich, N, Freimer, Nb, Fu, M, Gaget, S, Gejman, Pv, Geus, Ej, Gjesing, Ap, Goyette, P, Grässler, J, Greenawalt, Dm, Gudnason, V, Hartikainen, Al, Hall, As, Havulinna, As, Hayward, C, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hinney, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Jacobs, Kb, Jarick, I, Jewell, E, John, U, Jousilahti, P, Jula, A, Kaakinen, M, Kaplan, Lm, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, Jw, Kolcic, I, König, Ir, Koskinen, S, Kovacs, P, Kvaløy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, Lj, Lecoeur, C, Terho, L, Lettre, G, Liu, J, Lokki, Ml, Lorentzon, M, Luben, Rn, Ludwig, B, Magic, Manunta, P, Marek, D, Martin, Ng, Mcardle, Wl, Mccarthy, A, Mcknight, B, Melander, O, Meyre, D, Montgomery, Gw, Mulic, R, Ngwa, Js, Nelis, M, Neville, Mj, Nyholt, Dr, O'Donnell, Cj, O'Rahilly, S, Ong, Kk, Oostra, B, Paré, G, Parker, An, Perola, M, Pichler, I, Pietiläinen, Kh, Platou, Cg, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, Nw, Ridderstråle, M, Rief, W, Ruokonen, A, Rzehak, P, Salomaa, V, Sanders, Ar, Sandhu, Ms, Sanna, S, Saramies, J, Savolainen, Mj, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, Ds, Smit, Jh, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Tammesoo, Ml, Tardif, Jc, Teder Laving, M, Teslovich, Tm, Thompson, Jr, Thomson, B, Tönjes, A, van Meurs JB, van Ommen GJ, Vatin, V, Viikari, J, Visvikis Siest, S, Vitart, V, Vogel, Ci, Waite, Ll, Wallaschofski, H, Walters, Gb, Widen, E, Wiegand, S, Wild, Sh, Willemsen, G, Witte, Dr, Witteman, Jc, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, Jp, Farooqi, Is, Hebebrand, J, Huikuri, Hv, James, Al, Kähönen, M, Levinson, Df, Macciardi, F, Nieminen, Ms, Ohlsson, C, Palmer, Lj, Ridker, Pm, Stumvoll, M, Beckmann, Js, Boeing, H, Dorret, I. B., Caulfield, Mj, Chanock, Sj, Cupples, La, Smith, Gd, Erdmann, J, Grönberg, H, Hall, P, Harris, Tb, Hayes, Rb, Heinrich, J, Jarvelin, Mr, Kaprio, J, Karpe, F, Khaw, Kt, Kiemeney, La, Krude, H, Lawlor, Da, Metspalu, A, Munroe, Pb, Ouwehand, Wh, Penninx, Bw, Peters, A, Quertermous, T, Reinehr, T, Rissanen, A, Samani, Nj, Schwarz, Pe, Shuldiner, Ar, Spector, Td, Uda, M, Valle, Tt, Wabitsch, M, Waeber, G, Shaun, P, Eric, E. S., Peter, M. V., Assimes, Tl, Borecki, Ib, Groop, Lc, Haritunians, T, Kaplan, Rc, O'Connell, Jr, Peltonen, L, Schlessinger, D, Strachan, Dp, van Duijn CM, Barroso, H, North, Ke, Hirschhorn, Jn, Nica, Ac, Parts, L, Glass, D, Nisbet, J, Barrett, A, Sekowska, M, Travers, M, Potter, S, Grundberg, E, Small, K, Hedman, Åk, Bataille, V, Bell, Jt, Surdulescu, G, Ingle, C, Nestle, Fo, di Meglio, P, Min, Jl, Wilk, A, Hammond, Cj, Yang, Tp, Montgomery, Sb, Zondervan, Kt, Durbin, R, Ahmadi, K, Reilly, Mp, Holm, H, Stewart, Af, Barbalic, M, Absher, D, Aherrahrou, Z, Allayee, H, Anand, Ss, Andersen, K, Anderson, Jl, Ardissino, D, Ball, Sg, Barnes, Ta, Becker, Dm, Becker, Lc, Berger, K, Bis, Jc, Boekholdt, Sm, Braund, Ps, Burnett, Ms, Buysschaert, I, Cardiogenics, Carlquist, Jf, Chen, L, Cichon, S, Codd, V, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, Jm, Diemert, P, Do, R, Doering, A, Eifert, S, El Mokhtari NE, Ellis, Sg, Engert, Jc, Epstein, Se, de Faire, U, Fischer, M, Freyer, J, Gigante, B, Girelli, Domenico, Gretarsdottir, S, Gulcher, Jr, Halperin, E, Hammond, N, Hazen, Sl, Horne, Bd, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kastelein, Jj, Kolovou, G, Laaksonen, R, Lambrechts, D, Leander, K, Lieb, W, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meisinger, C, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Münzel, T, Musunuru, K, Nahrstaedt, J, Nelson, Cp, Nöthen, Mm, Olivieri, Oliviero, Patel, Rs, Patterson, Cc, Peyvandi, F, Qu, L, Quyyumi, Aa, Rader, Dj, Rallidis, Ls, Rice, C, Rosendaal, Fr, Rubin, D, Sampietro, Ml, Schadt, E, Schäfer, A, Schillert, A, Schrezenmeir, J, Schwartz, Sm, Sivananthan, M, Sivapalaratnam, S, Smith, A, Smith, Tb, Snoep, Jd, Spertus, Ja, Stark, K, Stoll, M, Tang, Wh, Tennstedt, S, Thorgeirsson, G, Tomaszewski, M, Uitterlinden, Ag, van Rij AM, Wells, Ga, Wichmann, He, Wild, Ps, Willenborg, C, Wright, Bj, Ye, S, Zeller, T, Cambien, F, Goodall, Ah, März, W, Blankenberg, S, Roberts, R, Mcpherson, R, Nilesh, J. S., Medical Research Council (MRC), Nica, Alexandra, Ongen, Halit, Dermitzakis, Emmanouil, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Vascular Medicine, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Scherag, Andre (Beitragende*r), Hinney, Anke (Beitragende*r), Scherag, S. (Beitragende*r), Vogel, C (Beitragende*r), Hebebrand, Johannes (Beitragende*r), University of Groningen, Wheeler, Eleanor [0000-0002-8616-6444], Barnes, Daniel [0000-0002-3781-7570], Luan, Jian'an [0000-0003-3137-6337], Johnson, Kathleen [0000-0002-6823-3252], Danesh, John [0000-0003-1158-6791], Wareham, Nicholas [0000-0003-1422-2993], Barroso, Ines [0000-0001-5800-4520], Langenberg, Claudia [0000-0002-5017-7344], and Apollo - University of Cambridge Repository

Subjects
Male, Netherlands Twin Register (NTR), endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Medizin, Genome-wide association study, Type 2 diabetes, CORONARY HEART-DISEASE, Fasting/blood, 0302 clinical medicine, Insulin, Glucose homeostasis, ddc:576.5, Genome-wide, Diabetes Mellitus, Type 2/blood/genetics/metabolism, CARDIoGRAM Consortium, POPULATION, Proinsulin, RISK, Genetics, 0303 health sciences, INSULIN SENSITIVITY, 11 Medical And Health Sciences, Fasting, Polymorphism, Single Nucleotide/genetics, OBESITY, Female, type 2 diabetes, Life Sciences & Biomedicine, hormones, hormone substitutes, and hormone antagonists, Insulin processing, Adult, medicine.medical_specialty, endocrine system, ENDOCRINOLOGY & METABOLISM, SUSCEPTIBILITY LOCI, Genotype, 030209 endocrinology & metabolism, DIAGRAM Consortium, Biology, C4D Consortium, Polymorphism, Single Nucleotide, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, Insulin resistance, BETA-CELL FUNCTION, SDG 3 - Good Health and Well-being, Internal medicine, GIANT Consortium, Internal Medicine, medicine, Humans, METAANALYSIS, 030304 developmental biology, Science & Technology, Genome, Human, Hormonal regulation [IGMD 6], Genetic Variation, nutritional and metabolic diseases, proinsulin, medicine.disease, Proinsulin/blood, TCF7L2, Endocrinology, Diabetes Mellitus, Type 2, MuTHER Consortium, GLUCOSE-HOMEOSTASIS, Insulin/blood
Abstract

OBJECTIVE Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-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 × 10−4), improved β-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.

Published
2011
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33. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

Author

Strawbridge, R.J. Dupuis, J. Prokopenko, I. Barker, A. Ahlqvist, E. Rybin, D. Petrie, J.R. Travers, M.E. Bouatia-Naji, N. Dimas, A.S. Nica, A.C. Wheeler, E. Chen, H. Voight, B.F. Taneera, J. Kanoni, S. Peden, J.F. Turrini, F. Gustafsson, S. Zabena, C. Almgren, P. Barker, D.J.P. Barnes, D. Dennison, E.M. Eriksson, J.G. Eriksson, P. Eury, E. Folkersen, L. Fox, C.S. Frayling, T.M. Goel, A. Gu, H.F. Horikoshi, M. Isomaa, B. Jackson, A.U. Jameson, K.A. Kajantie, E. Kerr-Conte, J. Kuulasmaa, T. Kuusisto, J. Loos, R.J.F. Luan, J. Makrilakis, K. Manning, A.K. Martínez-Larrad, M.T. Narisu, N. Mannila, M.N. Öhrvik, J. Osmond, C. Pascoe, L. Payne, F. Sayer, A.A. Sennblad, B. Silveira, A. Stančcáková, A. Stirrups, K. Swift, A.J. Syvänen, A.-C. Tuomi, T. Van't Hooft, F.M. Walker, M. Weedon, M.N. Xie, W. Zethelius, B. Scott, L.J. Steinthorsdottir, V. Morris, A.P. Dina, C. Welch, R.P. Zeggini, E. Huth, C. Aulchenko, Y.S. Thorleifsson, G. Mcculloch, L.J. Ferreira, T. Grallert, H. Amin, N. Wu, G. Willer, C.J. Raychaudhuri, S. McCarroll, S.A. Hofmann, O.M. Qi, L. Segre, A.V. Van Hoek, M. Navarro, P. Ardlie, K. Balkau, B. Benediktsson, R. Bennett, A.J. Blagieva, R. Boerwinkle, E. Bonnycastle, L.L. Bostrom, K.B. Bravenboer, B. Bumpstead, S. Burtt, N.P. Charpentier, G. Chines, P.S. Cornelis, M. Couper, D.J. Crawford, G. Doney, A.S.F. Elliott, K.S. Elliott, A.L. Erdos, M.R. Franklin, C.S. Ganser, M. Gieger, C. Grarup, N. Green, T. Griffin, S. Groves, C.J. Guiducci, C. Hadjadj, S. Hassanali, N. Herder, C. Johnson, P.R.V. Jorgensen, T. Kao, W.H.L. Klopp, N. Kong, A. Kraft, P. Lauritzen, T. Li, M. Lieverse, A. Lindgren, C.M. Lyssenko, V. Marre, M. Meitinger, T. Midthjell, K. Morken, M.A. Nilsson, P. Owen, K.R. Perry, J.R.B. Petersen, A.-K. Platou, C. Proenca, C. Rathmann, W. Rayner, N.W. Robertson, N.R. Rocheleau, G. Roden, M. Sampson, M.J. Saxena, R. Shields, B.M. Shrader, P. Sigurdsson, G. Sparso, T. Strassburger, K. Stringham, H.M. Sun, Q. Thorand, B. Tichet, J. Van Dam, R.M. Van Haeften, T.W. Van Herpt, T. Van Vliet-Ostaptchouk, J.V. Walters, G.B. Wijmenga, C. Witteman, J.C.M. Bergman, R.N. Cauchi, S. Collins, F.S. Gloyn, A.L. Gyllensten, U. Hansen, T. Hide, W.A. Hitman, G.A. Hofman, A. Hunter, D.J. Hveem, K. Laakso, M. Mohlke, K.L. Morris, A.D. Palmer, C.N.A. Pramstaller, P.P. Rudan, I. Sijbrands, E. Stein, L.D. Tuomilehto, J. Uitterlinden, A.G. Wareham, N.J. Watanabe, R.M. Abecasis, G.R. Boehm, B.O. Campbell, H. Daly, M.J. Hattersley, A.T. Hu, F.B. Meigs, J.B. Pankow, J.S. Pedersen, O. Wichmann, H.-E. Barroso, I. Groop, L. Sladek, R. Thorsteinsdottir, U. Wilson, J.F. Illig, T. Froguel, P. Van Duijn, C.M. Stefansson, K. Altshuler, D. Boehnke, M. McCarthy, M.I. Speliotes, E.K. Berndt, S.I. Monda, K.L. Allen, H.L. Magi, R. Randall, J.C. Vedantam, S. Winkler, T.W. Workalemahu, T. Heid, I.M. Wood, A.R. Weyant, R.J. Estrada, K. Liang, L. Nemesh, J. Park, J.-H. Kilpelainen, T.O. Yang, J. Esko, T. Feitosa, M.F. Kutalik, Z. Mangino, M. Scherag, A. Smith, A.V. Zhao, J.H. Aben, K.K. Absher, D.M. Dixon, A.L. Fisher, E. Glazer, N.L. Goddard, M.E. Heard-Costa, N.L. Hoesel, V. Hottenga, J.-J. Johansson, A. Johnson, T. Ketkar, S. Lamina, C. Li, S. Moffatt, M.F. Myers, R.H. Peters, M.J. Preuss, M. Ripatti, S. Rivadeneira, F. Sandholt, C. Timpson, N.J. Tyrer, J.P. Van Wingerden, S. White, C.C. Wiklund, F. Barlassina, C. Chasman, D.I. Cooper, M.N. Jansson, J.-O. Lawrence, R.W. Pellikka, N. Shi, J. Thiering, E. Alavere, H. Alibrandi, M.T.S. Arnold, A.M. Aspelund, T. Atwood, L.D. Balmforth, A.J. Ben-Shlomo, Y. Bergmann, S. Biebermann, H. Blakemore, A.I.F. Boes, T. Bornstein, S.R. Brown, M.J. Buchanan, T.A. Busonero, F. Cappuccio, F.P. Cavalcanti-Proenca, C. Chen, Y.-D.I. Chen, C.-M. Clarke, R. Coin, L. Connell, J. Day, I.N.M. Den Heijer, M. Duan, J. Ebrahim, S. Elliott, P. Elosua, R. Eiriksdottir, G. Facheris, M.F. Felix, S.B. Fischer-Posovszky, P. Folsom, A.R. Friedrich, N. Freimer, N.B. Fu, M. Gaget, S. Gejman, P.V. Geus, E.J.C. Gjesing, A.P. Goyette, P. Grasler, J. Greenawalt, D.M. Gudnason, V. Hartikainen, A.-L. Hall, A.S. Havulinna, A.S. Hayward, C. Heath, A.C. Hengstenberg, C. Hicks, A.A. Hinney, A. Homuth, G. Hui, J. Igl, W. Iribarren, C. Jacobs, K.B. Jarick, I. Jewell, E. John, U. Jousilahti, P. Jula, A. Kaakinen, M. Kaplan, L.M. Kathiresan, S. Kettunen, J. Kinnunen, L. Knowles, J.W. Kolcic, I. König, I.R. Koskinen, S. Kovacs, P. Kvaloy, K. Laitinen, J. Lantieri, O. Lanzani, C. Launer, L.J. Lecoeur, C. Lehtimaki, T. Lettre, G. Liu, J. Lokki, M.-L. Lorentzon, M. Luben, R.N. Ludwig, B. Manunta, P. Marek, D. Martin, N.G. McArdle, W.L. McCarthy, A. McKnight, B. Melander, O. Meyre, D. Montgomery, G.W. Mulic, R. Ngwa, J.S. Nelis, M. Neville, M.J. Nyholt, D.R. O'Donnell, C.J. O'Rahilly, S. Ong, K.K. Oostra, B. Pare, G. Parker, A.N. Perola, M. Pichler, I. Pietilainen, K.H. Platou, C.G.P. Polasek, O. Pouta, A. Rafelt, S. Raitakari, O. Rayner, N.W. Ridderstrale, M. Rief, W. Ruokonen, A. Rzehak, P. Salomaa, V. Sanders, A.R. Sandhu, M.S. Sanna, S. Saramies, J. Savolainen, M.J. Scherag, S. Schipf, S. Schreiber, S. Schunkert, H. Silander, K. Sinisalo, J. Siscovick, D.S. Smit, J.H. Soranzo, N. Sovio, U. Stephens, J. Surakka, I. Tammesoo, M.-L. Tardif, J.-C. Teder-Laving, M. Teslovich, T.M. Thompson, J.R. Thomson, B. Tonjes, A. Van Meurs, J.B.J. Van Ommen, G.-J. Vatin, V. Viikari, J. Visvikis-Siest, S. Vitart, V. Vogel, C.I.G. Waite, L.L. Wallaschofski, H. Widen, E. Wiegand, S. Wild, S.H. Willemsen, G. Witte, D.R. Xu, J. Zhang, Q. Zgaga, L. Ziegler, A. Zitting, P. Beilby, J.P. Farooqi, I.S. Hebebrand, J. Huikuri, H.V. James, A.L. Kahonen, M. Levinson, D.F. Macciardi, F. Nieminen, M.S. Ohlsson, C. Palmer, L.J. Ridker, P.M. Stumvoll, M. Beckmann, J.S. Boeing, H. Boomsma, D.I. Caulfield, M.J. Chanock, S.J. Cupples, L.A. Smith, G.D. Erdmann, J. Gronberg, H. Hall, P. Harris, T.B. Hayes, R.B. Heinrich, J. Jarvelin, M.-R. Kaprio, J. Karpe, F. Khaw, K.-T. Kiemeney, L.A. Krude, H. Lawlor, D.A. Metspalu, A. Munroe, P.B. Ouwehand, W.H. Penninx, B.W. Peters, A. Quertermous, T. Reinehr, T. Rissanen, A. Samani, N.J. Schwarz, P.E.H. Shuldiner, A.R. Spector, T.D. Uda, M. Valle, T.T. Wabitsch, M. Waeber, G. Watkins, H. Wright, A.F. Zillikens, M.C. Chatterjee, N. Purcell, S. Schadt, E.E. Visscher, P.M. Assimes, T.L. Borecki, I.B. Deloukas, P. Haritunians, T. Kaplan, R.C. O'Connell, J.R. Peltonen, L. Schlessinger, D. Strachan, D.P. North, K.E. Hirschhorn, J.N. Ingelsson, E. Parts, L. Glass, D. Nisbet, J. Barrett, A. Sekowska, M. Potter, S. Grundberg, E. Small, K. Hedman, A.K. Bataille, V. Bell, J.T. Surdulescu, G. Ingle, C. Nestle, F.O. Di Meglio, P. Min, J.L. Wilk, A. Hammond, C.J. Yang, T.-P. Montgomery, S.B. Zondervan, K.T. Durbin, R. Ahmadi, K. Dermitzakis, E.T. Reilly, M.P. Holm, H. Stewart, A.F.R. Barbalic, M. Aherrahrou, Z. Allayee, H. Anand, S.S. Andersen, K. Anderson, J.L. Ardissino, D. Ball, S.G. Barnes, T.A. Becker, D.M. Becker, L.C. Berger, K. Bis, J.C. Boekholdt, S.M. Braund, P.S. Burnett, M.S. Buysschaert, I. Carlquist, J.F. Chen, L. Codd, V. Davies, R.W. Cichon, S. Dedoussis, G.V. Demissie, S. Dehghan, A. Devaney, J.M. Diemert, P. Do, R. Doering, A. Eifert, S. El Mokhtari, N.E. Ellis, S.G. Engert, J.C. Epstein, S.E. De Faire, U. Fischer, M. Freyer, J. Gigante, B. Girelli, D. Gretarsdottir, S. Gulcher, J.R. Halperin, E. Hammond, N. Hazen, S.L. Horne, B.D. Jones, G.T. Jukema, J.W. Kaiser, M.A. Kastelein, J.J.P. Kolovou, G. Laaksonen, R. Lambrechts, D. Leander, K. Li, M. Lieb, W. Loley, C. Lotery, A.J. Mannucci, P.M. Maouche, S. Martinelli, N. McKeown, P.P. Meisinger, C. Merlini, P.A. Mooser, V. Morgan, T. Mühleisen, T.W. Muhlestein, J.B. Münzel, T. Musunuru, K. Nahrstaedt, J. Nelson, C.P. Nöthen, M.M. Olivieri, O. Patel, R.S. Patterson, C.C. Peyvandi, F. Qu, L. Quyyumi, A.A. Rader, D.J. Rallidis, L.S. Rice, C. Rosendaal, F.R. Rubin, D. Sampietro, M.L. Sandhu, M.S. Schadt, E. Schäfer, A. Schillert, A. Schrezenmeir, J. Schwartz, S.M. Sivananthan, M. Sivapalaratnam, S. Smith, T.B. Snoep, J.D. Spertus, J.A. Stark, K. Stoll, M. Wilson Tang, W.H. Tennstedt, S. Thorgeirsson, G. Tomaszewski, M. Van Rij, A.M. Wells, G.A. Wild, P.S. Willenborg, C. Wright, B.J. Ye, S. Zeller, T. Cambien, F. Goodall, A.H. Marz, W. Blankenberg, S. Roberts, R. McPherson, R. Hopewell, J.C. Parish, S. Offer, A. Bowman, L. Sleight, P. Armitage, J. Peto, R. Collins, R. Chambers, J.C. Ahmed, N. Donnelly, P. Kooner, A.S. Scott, J. Sehmi, J. Zhang, W. Kooner, J. Sabater-Lleal, M. Mälarstig, A. Hellénius, M.-L. Olsson, G. Rust, S. Assmann, G. Seedorf, U. Barlera, S. Tognoni, G. Franzosi, M.G. Linksted, P. Ongen, H. Kyriakou, T. Green, F. Farrall, M. Saleheen, D. Rasheed, A. Zaidi, M. Shah, N. Samuel, M. Mallick, N. Azhar, M. Zaman, K. Samad, A. Ishaq, M. Gardezi, A. Memon, F.-U.-R. Frossard, P. Danesh, J. Östenson, C.-G. Lind, L. Cooper, C.C. Serrano-Ríos, M. Ferrannini, E. Forsen, T.J. Pattou, F. Langenberg, C. Hamsten, A. Florez, J.C.

Subjects
endocrine system, endocrine system diseases, nutritional and metabolic diseases
Abstract

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 × 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. © 2011 by the American Diabetes Association.

Published
2011

34. Erratum: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk (Nature Genetics (2010) 42 (105-116))

Author

Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R, Soranzo, N, Jackson, AU, Wheeler, E, Glazer, NL, Bouatia-Naji, N, Gloyn, AL, Lindgren, CM, Mägi, R, Morris, AP, Randall, J, Johnson, T, Elliott, P, Rybin, D, Thorleifsson, G, Steinthorsdottir, V, Henneman, P, Grallert, H, Dehghan, A, Hottenga, JJ, Franklin, CS, Navarro, P, Song, K, Goel, A, Perry, JRB, Egan, JM, Lajunen, T, Grarup, N, Sparsø, T, Doney, A, Voight, BF, Stringham, HM, Li, M, Kanoni, S, Shrader, P, Cavalcanti-Proença, C, Kumari, M, Qi, L, Timpson, NJ, Gieger, C, Zabena, C, Rocheleau, G, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, McCarroll, SA, Payne, F, Roccasecca, RM, Pattou, F, Sethupathy, P, Ardlie, K, Ariyurek, Y, Balkau, B, Barter, P, Beilby, JP, Ben-Shlomo, Y, Benediktsson, R, Bennett, AJ, Bergmann, S, Bochud, M, Boerwinkle, E, Bonnefond, A, Bonnycastle, LL, Borch-Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, SJ, Charpentier, G, Chen, Y-DI, Chines, P, Clarke, R, Coin, LJM, Cooper, MN, Cornelis, M, Crawford, G, Crisponi, L, Day, INM, De Geus, EJC, Delplanque, J, Dina, C, Erdos, MR, Fedson, AC, Fischer-Rosinsky, A, Forouhi, NG, Fox, CS, Frants, R, Franzosi, MG, Galan, P, Goodarzi, MO, Graessler, J, Groves, CJ, Grundy, S, Gwilliam, R, Gyllensten, U, Hadjadj, S, Hallmans, G, Hammond, N, Han, X, Hartikainen, A-L, Hassanali, N, Hayward, C, Heath, SC, Hercberg, S, Herder, C, Hicks, AA, Hillman, DR, Hingorani, AD, Hofman, A, Hui, J, Hung, J, Isomaa, B, Johnson, PRV, Jørgensen, T, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, YA, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, KO, Lathrop, GM, Lawlor, DA, Le Bacquer, O, Lecoeur, C, Li, Y, Lyssenko, V, Mahley, R, Mangino, M, Manning, AK, Martínez-Larrad, MT, McAteer, JB, McCulloch, LJ, McPherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, BD, Morken, MA, Mukherjee, S, Naitza, S, Narisu, N, Neville, MJ, Oostra, BA, Orr, M, Pakyz, R, Palmer, CNA, Paolisso, G, Pattaro, C, Pearson, D, Peden, JF, Pedersen, NL, Perola, M, Pfeiffer, AFH, Pichler, I, Polasek, O, Posthuma, D, Potter, SC, Pouta, A, Province, MA, Psaty, BM, Rathmann, W, Rayner, NW, Rice, K, Ripatti, S, Rivadeneira, F, Roden, M, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, AA, Scheet, P, Scott, LJ, Seedorf, U, Sharp, SJ, Shields, B, Sigursson, G, Sijbrands, EJG, Silveira, A, Simpson, L, Singleton, A, Smith, NL, Sovio, U, Swift, A, Syddall, H, Syvänen, A-C, Tanaka, T, Thorand, B, Tichet, J, Tönjes, A, Tuomi, T, Uitterlinden, AG, Van Dijk, KW, Van Hoek, M, Varma, D, Visvikis-Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, PJ, Walley, A, Walters, GB, Ward, KL, Watkins, H, Weedon, MN, Wild, SH, Willemsen, G, Witteman, JCM, Yarnell, JWG, Zeggini, E, Zelenika, D, Zethelius, B, Zhai, G, Zhao, JH, Zillikens, MC, Consortium, D, Consortium, G, Consortium, GB, Borecki, IB, Loos, RJF, Meneton, P, Magnusson, PKE, Nathan, DM, Williams, GH, Hattersley, AT, Silander, K, Salomaa, V, Smith, GD, Bornstein, SR, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, AR, Cooper, C, Dedoussis, GV, Serrano-Ríos, M, Morris, AD, Lind, L, Palmer, LJ, Hu, FB, Franks, PW, Ebrahim, S, Marmot, M, Kao, WHL, Pankow, JS, Sampson, MJ, Kuusisto, J, Laakso, M, Hansen, T, Pedersen, O, Pramstaller, PP, Wichmann, HE, Illig, T, Rudan, I, Wright, AF, Stumvoll, M, Campbell, H, Wilson, JF, Hamsten, A, Bergman, RN, Buchanan, TA, Collins, FS, Mohlke, KL, Tuomilehto, J, Valle, TT, Altshuler, D, Rotter, JI, Siscovick, DS, Penninx, BWJH, Boomsma, DI, Deloukas, P, Spector, TD, Frayling, TM, Ferrucci, L, Kong, A, Thorsteinsdottir, U, Stefansson, K, Van Duijn, CM, Aulchenko, YS, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, M-R, Waterworth, DM, Vollenweider, P, Peltonen, L, Mooser, V, Abecasis, GR, Wareham, NJ, Sladek, R, Froguel, P, Watanabe, RM, Meigs, JB, Groop, L, Boehnke, M, McCarthy, MI, Florez, JC, and Barroso, I

Published
2010

35. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk (vol 42, pg 105, 2010)

Author

Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R, Soranzo, N, Jackson, AU, Wheeler, E, Glazer, NL, Bouatia-Naji, N, Gloyn, AL, Lindgren, CM, Maegi, R, Morris, AP, Randall, J, Johnson, T, Elliott, P, Rybin, D, Thorleifsson, G, Steinthorsdottir, V, Henneman, P, Grallert, H, Dehghan, A, Hottenga, JJ, Franklin, CS, Navarro, P, Song, K, Goel, A, Perry, JRB, Egan, JM, Lajunen, T, Grarup, N, Sparso, T, Doney, A, Voight, BF, Stringham, HM, Li, M, Kanoni, S, Shrader, P, Cavalcanti-Proenca, C, Kumari, M, Qi, L, Timpson, NJ, Gieger, C, Zabena, C, Rocheleau, G, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, McCarroll, SA, Payne, F, Roccasecca, RM, Pattou, F, Sethupathy, P, Ardlie, K, Ariyurek, Y, Balkau, B, Barter, P, Beilby, JP, Ben-Shlomo, Y, Benediktsson, R, Bennett, AJ, Bergmann, S, Bochud, M, Boerwinkle, E, Bonnefond, A, Bonnycastle, LL, Borch-Johnsen, K, Boettcher, Y, Brunner, E, Bumpstead, SJ, Charpentier, G, Chen, Y-DI, Chines, P, Clarke, R, Coin, LJM, Cooper, MN, Cornelis, M, Crawford, G, Crisponi, L, Day, INM, de Geus, EJC, Delplanque, J, Dina, C, Erdos, MR, Fedson, AC, Fischer-Rosinsky, A, Forouhi, NG, Fox, CS, Frants, R, Franzosi, MG, Galan, P, Goodarzi, MO, Graessler, J, Groves, CJ, Grundy, S, Gwilliam, R, Gyllensten, U, Hadjadj, S, Hallmans, G, Hammond, N, Han, X, Hartikainen, A-L, Hassanali, N, Hayward, C, Heath, SC, Hercberg, S, Herder, C, Hicks, AA, Hillman, DR, Hingorani, AD, Hofman, A, Hui, J, Hung, J, Isomaa, B, Johnson, PRV, Jorgensen, T, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, YA, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, KO, Lathrop, GM, Lawlor, DA, Le Bacquer, O, Lecoeur, C, Li, Y, Lyssenko, V, Mahley, R, Mangino, M, Manning, AK, Martinez-Larrad, MT, McAteer, JB, McCulloch, LJ, McPherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, BD, Morken, MA, Mukherjee, S, Naitza, S, Narisu, N, Neville, MJ, Oostra, BA, Orru, M, Pakyz, R, Palmer, CNA, Paolisso, G, Pattaro, C, Pearson, D, Peden, JF, Pedersen, NL, Perola, M, Pfeiffer, AFH, Pichler, I, Polasek, O, Posthuma, D, Potter, SC, Pouta, A, Province, MA, Psaty, BM, Rathmann, W, Rayner, NW, Rice, K, Ripatti, S, Rivadeneira, F, Roden, M, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, AA, Scheet, P, Scott, LJ, Seedorf, U, Sharp, SJ, Shields, B, Sigurosson, G, Sijbrands, EJG, Silveira, A, Simpson, L, Singleton, A, Smith, NL, Sovio, U, Swift, A, Syddall, H, Syvaenen, A-C, Tanaka, T, Thorand, B, Tichet, J, Toenjes, A, Tuomi, T, Uitterlinden, AG, van Dijk, KW, van Hoek, M, Varma, D, Visvikis-Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, PJ, Walley, A, Walters, GB, Ward, KL, Watkins, H, Weedon, MN, Wild, SH, Willemsen, G, Witteman, JCM, Yarnell, JWG, Zeggini, E, Zelenika, D, Zethelius, B, Zhai, G, Zhao, JH, Zillikens, MC, Borecki, IB, Loos, RJF, Meneton, P, Magnusson, PKE, Nathan, DM, Williams, GH, Hattersley, AT, Silander, K, Salomaa, V, Smith, GD, Bornstein, SR, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, AR, Cooper, C, Dedoussis, GV, Serrano-Rios, M, Morris, AD, Lind, L, Palmer, LJ, Hu, FB, Franks, PW, Ebrahim, S, Marmot, M, Kao, WHL, Pankow, JS, Sampson, MJ, Kuusisto, J, Laakso, M, Hansen, T, Pedersen, O, Pramstaller, PP, Wichmann, HE, Illig, T, Rudan, I, Wright, AF, Stumvoll, M, Campbell, H, Wilson, JF, Hamsten, A, Bergman, RN, Buchanan, TA, Collins, FS, Mohlke, KL, Tuomilehto, J, Valle, TT, Altshuler, D, Rotter, JI, Siscovick, DS, Penninx, BWJH, Boomsma, DI, Deloukas, P, Spector, TD, Frayling, TM, Ferrucci, L, Kong, A, Thorsteinsdottir, U, Stefansson, K, van Duijn, CM, Aulchenko, YS, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, M-R, Waterworth, DM, Vollenweider, P, Peltonen, L, Mooser, V, Abecasis, GR, Wareham, NJ, Sladek, R, Froguel, P, Watanabe, RM, Meigs, JB, Groop, L, Boehnke, M, McCarthy, MI, Florez, JC, Consortium, DIAGRAM, Consortium, GIANT, Consortium, GB, Consortium, P, and Investigators, IBMAGIC

Published
2010

37. A genetic variant inSLC6A20is associated with Type 2 diabetes in white-European and Chinese populations

Author

Ling, Y., primary, van Herpt, T. T. W., additional, van Hoek, M., additional, Dehghan, A., additional, Hofman, A., additional, Uitterlinden, A. G., additional, Jiang, S., additional, Lieverse, A. G., additional, Bravenboer, B., additional, Lu, D., additional, van Duijn, C. M., additional, Gao, X., additional, and Sijbrands, E. J. G., additional

Published
2014
Full Text
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39. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Author

DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Multiple Tissue Human Expression Resource (MUTHER) Consortium, Ahmadi, K.R., Ainali, C., Barrett, A., Bataille, V., Bell, J.T., Buil, A., Deloukas, P., Dermitzakis, E.T., Dimas, A.S., Durbin, R., Glass, D., Grundberg, E., Hassanali, N., Hedman, Å.K., Ingle, C., Knowles, D., Krestyaninova, M., Lindgren, C.M., Lowe, C.E., McCarthy, M.I., Meduri, E., di Meglio, P., Min, J.L., Montgomery, S.B., Nestle, F.O., Nica, A.C., Nisbet, J., O'Rahilly, S., Parts, L., Potter, S., Sekowska, M., Shin, S.Y., Small, K.S., Soranzo, N., Spector, T.D., Surdulescu, G., Travers, M.E., Tsaprouni, L., Tsoka, S., Wilk, A., Yang, T.P., Zondervan, K.T., Voight, B.F., Scott, L.J., Steinthorsdottir, V., Morris, A.P., Dina, C., Welch, R.P., Zeggini, E., Huth, C., Aulchenko, Y.S., Thorleifsson, G., McCulloch, L.J., Ferreira, T., Grallert, H., Amin, N., Wu, G., Willer, C.J., Raychaudhuri, S., McCarroll, S.A., Langenberg, C., Hofmann, O.M., Dupuis, J., Qi, L., Segrè, A.V., van Hoek, M., Navarro, P., Ardlie, K., Balkau, B., Benediktsson, R., Bennett, A.J., Blagieva, R., Boerwinkle, E., Bonnycastle, L.L., Boström, K.B., Bravenboer, B., Bumpstead, S., Burtt, N.P., Charpentier, G., Chines, P.S., Cornelis, M., Couper, D.J., Crawford, G., Doney, A.S., Elliott, K.S., Elliott, A.L., Erdos, M.R., Fox, C.S., Franklin, C.S., Ganser, M., Gieger, C., Grarup, N., Green, T., Griffin, S., Groves, C.J., Guiducci, C., Hadjadj, S., Herder, C., Isomaa, B., Jackson, A.U., Johnson, P.R., Jørgensen, T., Kao, W.H., Klopp, N., Kong, A., Kraft, P., Kuusisto, J., Lauritzen, T., Li, M., Lieverse, A., Lyssenko, V., Marre, M., Meitinger, T., Midthjell, K., Morken, M.A., Narisu, N., Nilsson, P., Owen, K.R., Payne, F., Perry, J.R., Petersen, A.K., Platou, C., Proença, C., Prokopenko, I., Rathmann, W., Rayner, N.W., Robertson, N.R., Rocheleau, G., Roden, M., Sampson, M.J., Saxena, R., Shields, B.M., Shrader, P., Sigurdsson, G., Sparsø, T., Strassburger, K., Stringham, H.M., Sun, Q., Swift, A.J., Thorand, B., Tichet, J., Tuomi, T., van Dam, R.M., van Haeften, T.W., van Herpt, T., van Vliet-Ostaptchouk, J.V., Walters, G.B., Weedon, M.N., Wijmenga, C., Witteman, J., Bergman, R.N., Cauchi, S., Collins, F.S., Gloyn, A.L., Gyllensten, U., Hansen, T., Hide, W.A., Hitman, G.A., Hofman, A., Hunter, D.J., Hveem, K., Laakso, M., Mohlke, K.L., Morris, A.D., Palmer, C.N., Pramstaller, P.P., Rudan, I., Sijbrands, E., Stein, L.D., Tuomilehto, J., Uitterlinden, A., Walker, M., Wareham, N.J., Watanabe, R.M., Abecasis, G.R., Boehm, B.O., Campbell, H., Daly, M.J., Hattersley, A.T., Hu, F.B., Meigs, J.B., Pankow, J.S., Pedersen, O., Wichmann, H.E., Barroso, I., Florez, J.C., Frayling, T.M., Groop, L., Sladek, R., Thorsteinsdottir, U., Wilson, J.F., Illig, T., Froguel, P., van Duijn, C.M., Stefansson, K., Altshuler, D., Boehnke, M., Manning, A.K., Hivert, M.F., Scott, R.A., Grimsby, J.L., Bouatia-Naji, N., Chen, H., Rybin, D., Liu, C.T., Bielak, L.F., Barnes, D., Cadby, G., Hottenga, J.J., Ingelsson, E., Johnson, T., Kanoni, S., Ladenvall, C., Lagou, V., Lahti, J., Lecoeur, C., Liu, Y., Martinez-Larrad, M.T., Montasser, M.E., Rasmussen-Torvik, L.J., Salo, P., Sattar, N., Shungin, D., Strawbridge, R.J., Tanaka, T., An, P., de Andrade, M., Andrews, J.S., Aspelund, T., Atalay, M., Aulchenko, Y., Bandinelli, S., Beckmann, J.S., Beilby, J.P., Bellis, C., Blangero, J., Boban, M., Boomsma, D.I., Borecki, I.B., Böttcher, Y., Bouchard, C., Brunner, E., Budimir, D., Carlson, O., Clarke, R., Corbatón-Anchuelo, A., Couper, D., de Faire, U., Dedoussis, G.V., Dimitriou, M., Egan, J.M., Eiriksdottir, G., Eriksson, J.G., Eury, E., Ferrucci, L., Ford, I., Forouhi, N.G., Franzosi, M.G., Franks, P.W., Galan, P., de Geus, E., Gigante, B., Glazer, N.L., Goel, A., Gudnason, V., Hallmans, G., Hamsten, A., Hansson, O., Harris, T.B., Hayward, C., Heath, S., Hercberg, S., Hicks, A.A., Hingorani, A., Hui, J., Hung, J., Jarvelin, M.R., Jhun, M.A., Johnson, P.C., Jukema, J.W., Jula, A., Kaprio, J., Kardia, S.L., Keinanen-Kiukaanniemi, S., Kivimaki, M., Kolcic, I., Kovacs, P., Kumari, M., Kyvik, K.O., Lakka, T., Lannfelt, L., Lathrop, G.M., Launer, L.J., Leander, K., Li, G., Lind, L., Lindstrom, J., Lobbens, S., Loos, R.J., Luan, J., Mägi, R., Magnusson, P.K., Marmot, M., Meneton, P., Mooser, V., Miljkovic, I., O'Connell, J., Ong, K.K., Oostra, B.A., Palmer, L.J., Palotie, A., Peden, J.F., Pedersen, N.L., Pehlic, M., Peltonen, L., Penninx, B., Pericic, M., Perola, M., Perusse, L., Peyser, P.A., Polasek, O., Province, M.A., Räikkönen, K., Rauramaa, R., Rehnberg, E., Rice, K., Rotter, J.I., Ruokonen, A., Saaristo, T., Sabater-Lleal, M., Salomaa, V., Savage, D.B., Schwarz, P., Seedorf, U., Sennblad, B., Serrano-Rios, M., Shuldiner, A.R., Sijbrands, E.J., Siscovick, D.S., Smit, J.H., Smith, N.L., Smith, A.V., Stančáková, A., Stirrups, K., Stumvoll, M., Sun, Y.V., Tönjes, A., Trompet, S., Uitterlinden, A.G., Uusitupa, M., Vikström, M., Vitart, V., Vohl, M.C., Vollenweider, P., Waeber, G., Waterworth, D.M., Watkins, H., Wheeler, E., Widen, E., Wild, S.H., Willems, S.M., Willemsen, G., Witteman, J.C., Wright, A.F., Yaghootkar, H., Zelenika, D., Zemunik, T., Zgaga, L., DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Multiple Tissue Human Expression Resource (MUTHER) Consortium, Ahmadi, K.R., Ainali, C., Barrett, A., Bataille, V., Bell, J.T., Buil, A., Deloukas, P., Dermitzakis, E.T., Dimas, A.S., Durbin, R., Glass, D., Grundberg, E., Hassanali, N., Hedman, Å.K., Ingle, C., Knowles, D., Krestyaninova, M., Lindgren, C.M., Lowe, C.E., McCarthy, M.I., Meduri, E., di Meglio, P., Min, J.L., Montgomery, S.B., Nestle, F.O., Nica, A.C., Nisbet, J., O'Rahilly, S., Parts, L., Potter, S., Sekowska, M., Shin, S.Y., Small, K.S., Soranzo, N., Spector, T.D., Surdulescu, G., Travers, M.E., Tsaprouni, L., Tsoka, S., Wilk, A., Yang, T.P., Zondervan, K.T., Voight, B.F., Scott, L.J., Steinthorsdottir, V., Morris, A.P., Dina, C., Welch, R.P., Zeggini, E., Huth, C., Aulchenko, Y.S., Thorleifsson, G., McCulloch, L.J., Ferreira, T., Grallert, H., Amin, N., Wu, G., Willer, C.J., Raychaudhuri, S., McCarroll, S.A., Langenberg, C., Hofmann, O.M., Dupuis, J., Qi, L., Segrè, A.V., van Hoek, M., Navarro, P., Ardlie, K., Balkau, B., Benediktsson, R., Bennett, A.J., Blagieva, R., Boerwinkle, E., Bonnycastle, L.L., Boström, K.B., Bravenboer, B., Bumpstead, S., Burtt, N.P., Charpentier, G., Chines, P.S., Cornelis, M., Couper, D.J., Crawford, G., Doney, A.S., Elliott, K.S., Elliott, A.L., Erdos, M.R., Fox, C.S., Franklin, C.S., Ganser, M., Gieger, C., Grarup, N., Green, T., Griffin, S., Groves, C.J., Guiducci, C., Hadjadj, S., Herder, C., Isomaa, B., Jackson, A.U., Johnson, P.R., Jørgensen, T., Kao, W.H., Klopp, N., Kong, A., Kraft, P., Kuusisto, J., Lauritzen, T., Li, M., Lieverse, A., Lyssenko, V., Marre, M., Meitinger, T., Midthjell, K., Morken, M.A., Narisu, N., Nilsson, P., Owen, K.R., Payne, F., Perry, J.R., Petersen, A.K., Platou, C., Proença, C., Prokopenko, I., Rathmann, W., Rayner, N.W., Robertson, N.R., Rocheleau, G., Roden, M., Sampson, M.J., Saxena, R., Shields, B.M., Shrader, P., Sigurdsson, G., Sparsø, T., Strassburger, K., Stringham, H.M., Sun, Q., Swift, A.J., Thorand, B., Tichet, J., Tuomi, T., van Dam, R.M., van Haeften, T.W., van Herpt, T., van Vliet-Ostaptchouk, J.V., Walters, G.B., Weedon, M.N., Wijmenga, C., Witteman, J., Bergman, R.N., Cauchi, S., Collins, F.S., Gloyn, A.L., Gyllensten, U., Hansen, T., Hide, W.A., Hitman, G.A., Hofman, A., Hunter, D.J., Hveem, K., Laakso, M., Mohlke, K.L., Morris, A.D., Palmer, C.N., Pramstaller, P.P., Rudan, I., Sijbrands, E., Stein, L.D., Tuomilehto, J., Uitterlinden, A., Walker, M., Wareham, N.J., Watanabe, R.M., Abecasis, G.R., Boehm, B.O., Campbell, H., Daly, M.J., Hattersley, A.T., Hu, F.B., Meigs, J.B., Pankow, J.S., Pedersen, O., Wichmann, H.E., Barroso, I., Florez, J.C., Frayling, T.M., Groop, L., Sladek, R., Thorsteinsdottir, U., Wilson, J.F., Illig, T., Froguel, P., van Duijn, C.M., Stefansson, K., Altshuler, D., Boehnke, M., Manning, A.K., Hivert, M.F., Scott, R.A., Grimsby, J.L., Bouatia-Naji, N., Chen, H., Rybin, D., Liu, C.T., Bielak, L.F., Barnes, D., Cadby, G., Hottenga, J.J., Ingelsson, E., Johnson, T., Kanoni, S., Ladenvall, C., Lagou, V., Lahti, J., Lecoeur, C., Liu, Y., Martinez-Larrad, M.T., Montasser, M.E., Rasmussen-Torvik, L.J., Salo, P., Sattar, N., Shungin, D., Strawbridge, R.J., Tanaka, T., An, P., de Andrade, M., Andrews, J.S., Aspelund, T., Atalay, M., Aulchenko, Y., Bandinelli, S., Beckmann, J.S., Beilby, J.P., Bellis, C., Blangero, J., Boban, M., Boomsma, D.I., Borecki, I.B., Böttcher, Y., Bouchard, C., Brunner, E., Budimir, D., Carlson, O., Clarke, R., Corbatón-Anchuelo, A., Couper, D., de Faire, U., Dedoussis, G.V., Dimitriou, M., Egan, J.M., Eiriksdottir, G., Eriksson, J.G., Eury, E., Ferrucci, L., Ford, I., Forouhi, N.G., Franzosi, M.G., Franks, P.W., Galan, P., de Geus, E., Gigante, B., Glazer, N.L., Goel, A., Gudnason, V., Hallmans, G., Hamsten, A., Hansson, O., Harris, T.B., Hayward, C., Heath, S., Hercberg, S., Hicks, A.A., Hingorani, A., Hui, J., Hung, J., Jarvelin, M.R., Jhun, M.A., Johnson, P.C., Jukema, J.W., Jula, A., Kaprio, J., Kardia, S.L., Keinanen-Kiukaanniemi, S., Kivimaki, M., Kolcic, I., Kovacs, P., Kumari, M., Kyvik, K.O., Lakka, T., Lannfelt, L., Lathrop, G.M., Launer, L.J., Leander, K., Li, G., Lind, L., Lindstrom, J., Lobbens, S., Loos, R.J., Luan, J., Mägi, R., Magnusson, P.K., Marmot, M., Meneton, P., Mooser, V., Miljkovic, I., O'Connell, J., Ong, K.K., Oostra, B.A., Palmer, L.J., Palotie, A., Peden, J.F., Pedersen, N.L., Pehlic, M., Peltonen, L., Penninx, B., Pericic, M., Perola, M., Perusse, L., Peyser, P.A., Polasek, O., Province, M.A., Räikkönen, K., Rauramaa, R., Rehnberg, E., Rice, K., Rotter, J.I., Ruokonen, A., Saaristo, T., Sabater-Lleal, M., Salomaa, V., Savage, D.B., Schwarz, P., Seedorf, U., Sennblad, B., Serrano-Rios, M., Shuldiner, A.R., Sijbrands, E.J., Siscovick, D.S., Smit, J.H., Smith, N.L., Smith, A.V., Stančáková, A., Stirrups, K., Stumvoll, M., Sun, Y.V., Tönjes, A., Trompet, S., Uitterlinden, A.G., Uusitupa, M., Vikström, M., Vitart, V., Vohl, M.C., Vollenweider, P., Waeber, G., Waterworth, D.M., Watkins, H., Wheeler, E., Widen, E., Wild, S.H., Willems, S.M., Willemsen, G., Witteman, J.C., Wright, A.F., Yaghootkar, H., Zelenika, D., Zemunik, T., and Zgaga, L.

Abstract

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

Published
2012

40. 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

DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC investigators, GLGC Consortium, Olson, J., Kronmal, R., Robbins, J., Chaves, PH., Burke, G., Kuller, LH., Tracy, R., Gottdiener, J., Prineas, R., Becker, JT., Enright, P., Klein, R., O'Leary, DH., Dastani, Z., Hivert, M.F., Timpson, N., Perry, J.R., Yuan, X., Scott, R.A., Henneman, P., Heid, I.M., Kizer, J.R., Lyytikäinen, L.P., Fuchsberger, C., Tanaka, T., Morris, A.P., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, J.S., Uh, H.W., Wu, Y., Bidulescu, A., Rasmussen-Torvik, L.J., Greenwood, C.M., Ladouceur, M., Grimsby, J., Manning, A.K., Liu, C.T., Kooner, J., Mooser, V.E., Vollenweider, P., Kapur, K.A., Chambers, J., Wareham, N.J., Langenberg, C., Frants, R., Willems-Vandijk, K., Oostra, B.A., Willems, S.M., Lamina, C., Winkler, T.W., Psaty, B.M., Tracy, R.P., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, P.P., Evans, D.M., St Pourcain, B., Sattar, N., Wood, A.R., Bandinelli, S., Carlson, O.D., Egan, J.M., Böhringer, S., van Heemst, D., Kedenko, L., Kristiansson, K., Nuotio, M.L., Loo, B.M., Harris, T., Garcia, M., Kanaya, A., Haun, M., Klopp, N., Wichmann, H.E., Deloukas, P., Katsareli, E., Couper, D.J., Duncan, B.B., Kloppenburg, M., Adair, L.S., Borja, J.B., Wilson, J.G., Musani, S., Guo, X., Johnson, T., Semple, R., Teslovich, T.M., Allison, M.A., Redline, S., Buxbaum, S.G., Mohlke, K.L., Meulenbelt, I., Ballantyne, C.M., Dedoussis, G.V., Hu, F.B., Liu, Y., Paulweber, B., Spector, T.D., Slagboom, P.E., Ferrucci, L., Jula, A., Perola, M., Raitakari, O., Florez, J.C., Salomaa, V., Eriksson, J.G., Frayling, T.M., Hicks, A.A., Lehtimäki, T., Smith, G.D., Siscovick, D.S., Kronenberg, F., van Duijn, C., Loos, R.J., Waterworth, D.M., Meigs, J.B., Dupuis, J., Richards, J.B., Voight, B.F., Scott, L.J., Steinthorsdottir, V., Dina, C., Welch, R.P., Zeggini, E., Huth, C., Aulchenko, Y.S., Thorleifsson, G., McCulloch, L.J., Ferreira, T., Grallert, H., Amin, N., Wu, G., Willer, C.J., Raychaudhuri, S., McCarroll, S.A., Hofmann, O.M., Segrè, A.V., van Hoek, M., Navarro, P., Ardlie, K., Balkau, B., Benediktsson, R., Bennett, A.J., Blagieva, R., Boerwinkle, E., Bonnycastle, L.L., Boström, K.B., Bravenboer, B., Bumpstead, S., Burtt, N.P., Charpentier, G., Chines, P.S., Cornelis, M., Crawford, G., Doney, A.S., Elliott, K.S., Elliott, A.L., Erdos, M.R., Fox, C.S., Franklin, C.S., Ganser, M., Gieger, C., Grarup, N., Green, T., Griffin, S., Groves, C.J., Guiducci, C., Hadjadj, S., Hassanali, N., Herder, C., Isomaa, B., Jackson, A.U., Johnson, P.R., Jørgensen, T., Kao, W.H., Kong, A., Kraft, P., Kuusisto, J., Lauritzen, T., Li, M., Lieverse, A., Lindgren, C.M., Lyssenko, V., Marre, M., Meitinger, T., Midthjell, K., Morken, M.A., Narisu, N., Nilsson, P., Owen, K.R., Payne, F., Petersen, A.K., Platou, C., Proença, C., Prokopenko, I., Rathmann, W., Rayner, N.W., Robertson, N.R., Rocheleau, G., Roden, M., Sampson, M.J., Saxena, R., Shields, B.M., Shrader, P., Sigurdsson, G., Sparsø, T., Strassburger, K., Stringham, H.M., Sun, Q., Swift, A.J., Thorand, B., Tichet, J., Tuomi, T., van Dam, R.M., van Haeften, T.W., van Herpt, T., van Vliet-Ostaptchouk, J.V., Walters, G.B., Weedon, M.N., Wijmenga, C., Witteman, J., Bergman, R.N., Cauchi, S., Collins, F.S., Gloyn, A.L., Gyllensten, U., Hansen, T., Hide, W.A., Hitman, G.A., Hofman, A., Hunter, D.J., Hveem, K., Laakso, M., Morris, A.D., Palmer, C.N., Rudan, I., Sijbrands, E., Stein, L.D., Tuomilehto, J., Uitterlinden, A., Walker, M., Watanabe, R.M., Abecasis, G.R., Boehm, B.O., Campbell, H., Daly, M.J., Hattersley, A.T., Pedersen, O., Barroso, I., Groop, L., Sladek, R., Thorsteinsdottir, U., Wilson, J.F., Illig, T., Froguel, P., van Duijn, C.M., Stefansson, K., Altshuler, D., Boehnke, M., McCarthy, M.I., Soranzo, N., Wheeler, E., Glazer, N.L., Bouatia-Naji, N., Mägi, R., Randall, J., Elliott, P., Rybin, D., Dehghan, A., Hottenga, J.J., Song, K., Goel, A., Lajunen, T., Doney, A., Cavalcanti-Proença, C., Kumari, M., Timpson, N.J., Zabena, C., Ingelsson, E., An, P., O'Connell, J., Luan, J., Elliott, A., Roccasecca, R.M., Pattou, F., Sethupathy, P., Ariyurek, Y., Barter, P., Beilby, J.P., Ben-Shlomo, Y., Bergmann, S., Bochud, M., Bonnefond, A., Borch-Johnsen, K., Böttcher, Y., Brunner, E., Bumpstead, S.J., Chen, Y.D., Chines, P., Clarke, R., Coin, L.J., Cooper, M.N., Crisponi, L., Day, I.N., de Geus, E.J., Delplanque, J., Fedson, A.C., Fischer-Rosinsky, A., Forouhi, N.G., Franzosi, M.G., Galan, P., Goodarzi, M.O., Graessler, J., Grundy, S., Gwilliam, R., Hallmans, G., Hammond, N., Han, X., Hartikainen, A.L., Hayward, C., Heath, S.C., Hercberg, S., Hillman, D.R., Hingorani, A.D., Hui, J., Hung, J., Kaakinen, M., Kaprio, J., Kesaniemi, Y.A., Kivimaki, M., Knight, B., Koskinen, S., Kovacs, P., Kyvik, K.O., Lathrop, G.M., Lawlor, D.A., Le Bacquer, O., Lecoeur, C., Li, Y., Mahley, R., Mangino, M., Martínez-Larrad, M.T., McAteer, J.B., McPherson, R., Meisinger, C., Melzer, D., Meyre, D., Mitchell, B.D., Mukherjee, S., Naitza, S., Neville, M.J., Orrù, M., Pakyz, R., Paolisso, G., Pattaro, C., Pearson, D., Peden, J.F., Pedersen, N.L., Pfeiffer, A.F., Pichler, I., Polasek, O., Posthuma, D., Potter, S.C., Pouta, A., Province, M.A., Rice, K., Ripatti, S., Rivadeneira, F., Rolandsson, O., Sandbaek, A., Sandhu, M., Sanna, S., Sayer, A.A., Scheet, P., Seedorf, U., Sharp, S.J., Shields, B., Sigurðsson, G., Sijbrands, E.J., Silveira, A., Simpson, L., Singleton, A., Smith, N.L., Sovio, U., Swift, A., Syddall, H., Syvänen, A.C., Tönjes, A., Uitterlinden, A.G., van Dijk, K.W., Varma, D., Visvikis-Siest, S., Vitart, V., Vogelzangs, N., Waeber, G., Wagner, P.J., Walley, A., Ward, K.L., Watkins, H., Wild, S.H., Willemsen, G., Witteman, J.C., Yarnell, J.W., Zelenika, D., Zethelius, B., Zhai, G., Zhao, J.H., Zillikens, M.C., Borecki, I.B., Meneton, P., Magnusson, P.K., Nathan, D.M., Williams, G.H., Silander, K., Bornstein, S.R., Schwarz, P., Spranger, J., Karpe, F., Shuldiner, A.R., Cooper, C., Serrano-Ríos, M., Lind, L., Palmer, L.J., Franks, P.W., Ebrahim, S., Marmot, M., Wright, A.F., Stumvoll, M., Hamsten, A., Buchanan, T.A., Valle, T.T., Rotter, J.I., Penninx, B.W., Boomsma, D.I., Cao, A., Scuteri, A., Schlessinger, D., Uda, M., Ruokonen, A., Jarvelin, M.R., Peltonen, L., Mooser, V., Musunuru, K., Smith, A.V., Edmondson, A.C., Stylianou, I.M., Koseki, M., Pirruccello, J.P., Chasman, D.I., Johansen, C.T., Fouchier, S.W., Peloso, G.M., Barbalic, M., Ricketts, S.L., Bis, J.C., Feitosa, M.F., Orho-Melander, M., Melander, O., Li, X., Cho, Y.S., Go, M.J., Kim, Y.J., Lee, J.Y., Park, T., Kim, K., Sim, X., Ong, R.T., Croteau-Chonka, D.C., Lange, L.A., Smith, J.D., Ziegler, A., Zhang, W., Zee, R.Y., Whitfield, J.B., Thompson, J.R., Surakka, I., Smit, J.H., Sinisalo, J., Scott, J., Saharinen, J., Sabatti, C., Rose, L.M., Roberts, R., Rieder, M., Parker, A.N., Pare, G., O'Donnell, C.J., Nieminen, M.S., Nickerson, D.A., Montgomery, G.W., McArdle, W., Masson, D., Martin, N.G., Marroni, F., Lucas, G., Luben, R., Lokki, M.L., Lettre, G., Launer, L.J., Lakatta, E.G., Laaksonen, R., König, I.R., Khaw, K.T., Kaplan, L.M., Johansson, Å., Janssens, A.C., Igl, W., Hovingh, G.K., Hengstenberg, C., Havulinna, A.S., Hastie, N.D., Harris, T.B., Haritunians, T., Hall, A.S., Groop, L.C., Gonzalez, E., Freimer, N.B., Erdmann, J., Ejebe, K.G., Döring, A., Dominiczak, A.F., Demissie, S., de Faire, U., Caulfield, M.J., Boekholdt, S.M., Assimes, T.L., Quertermous, T., Seielstad, M., Wong, T.Y., Tai, E.S., Feranil, A.B., Kuzawa, C.W., Taylor, H.A., Gabriel, S.B., Holm, H., Gudnason, V., Krauss, R.M., Ordovas, J.M., Munroe, P.B., Kooner, J.S., Tall, A.R., Hegele, R.A., Kastelein, J.J., Schadt, E.E., Strachan, D.P., Reilly, M.P., Samani, N.J., Schunkert, H., Cupples, L.A., Sandhu, M.S., Ridker, P.M., Rader, D.J., Kathiresan, S., DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC investigators, GLGC Consortium, Olson, J., Kronmal, R., Robbins, J., Chaves, PH., Burke, G., Kuller, LH., Tracy, R., Gottdiener, J., Prineas, R., Becker, JT., Enright, P., Klein, R., O'Leary, DH., Dastani, Z., Hivert, M.F., Timpson, N., Perry, J.R., Yuan, X., Scott, R.A., Henneman, P., Heid, I.M., Kizer, J.R., Lyytikäinen, L.P., Fuchsberger, C., Tanaka, T., Morris, A.P., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, J.S., Uh, H.W., Wu, Y., Bidulescu, A., Rasmussen-Torvik, L.J., Greenwood, C.M., Ladouceur, M., Grimsby, J., Manning, A.K., Liu, C.T., Kooner, J., Mooser, V.E., Vollenweider, P., Kapur, K.A., Chambers, J., Wareham, N.J., Langenberg, C., Frants, R., Willems-Vandijk, K., Oostra, B.A., Willems, S.M., Lamina, C., Winkler, T.W., Psaty, B.M., Tracy, R.P., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, P.P., Evans, D.M., St Pourcain, B., Sattar, N., Wood, A.R., Bandinelli, S., Carlson, O.D., Egan, J.M., Böhringer, S., van Heemst, D., Kedenko, L., Kristiansson, K., Nuotio, M.L., Loo, B.M., Harris, T., Garcia, M., Kanaya, A., Haun, M., Klopp, N., Wichmann, H.E., Deloukas, P., Katsareli, E., Couper, D.J., Duncan, B.B., Kloppenburg, M., Adair, L.S., Borja, J.B., Wilson, J.G., Musani, S., Guo, X., Johnson, T., Semple, R., Teslovich, T.M., Allison, M.A., Redline, S., Buxbaum, S.G., Mohlke, K.L., Meulenbelt, I., Ballantyne, C.M., Dedoussis, G.V., Hu, F.B., Liu, Y., Paulweber, B., Spector, T.D., Slagboom, P.E., Ferrucci, L., Jula, A., Perola, M., Raitakari, O., Florez, J.C., Salomaa, V., Eriksson, J.G., Frayling, T.M., Hicks, A.A., Lehtimäki, T., Smith, G.D., Siscovick, D.S., Kronenberg, F., van Duijn, C., Loos, R.J., Waterworth, D.M., Meigs, J.B., Dupuis, J., Richards, J.B., Voight, B.F., Scott, L.J., Steinthorsdottir, V., Dina, C., Welch, R.P., Zeggini, E., Huth, C., Aulchenko, Y.S., Thorleifsson, G., McCulloch, L.J., Ferreira, T., Grallert, H., Amin, N., Wu, G., Willer, C.J., Raychaudhuri, S., McCarroll, S.A., Hofmann, O.M., Segrè, A.V., van Hoek, M., Navarro, P., Ardlie, K., Balkau, B., Benediktsson, R., Bennett, A.J., Blagieva, R., Boerwinkle, E., Bonnycastle, L.L., Boström, K.B., Bravenboer, B., Bumpstead, S., Burtt, N.P., Charpentier, G., Chines, P.S., Cornelis, M., Crawford, G., Doney, A.S., Elliott, K.S., Elliott, A.L., Erdos, M.R., Fox, C.S., Franklin, C.S., Ganser, M., Gieger, C., Grarup, N., Green, T., Griffin, S., Groves, C.J., Guiducci, C., Hadjadj, S., Hassanali, N., Herder, C., Isomaa, B., Jackson, A.U., Johnson, P.R., Jørgensen, T., Kao, W.H., Kong, A., Kraft, P., Kuusisto, J., Lauritzen, T., Li, M., Lieverse, A., Lindgren, C.M., Lyssenko, V., Marre, M., Meitinger, T., Midthjell, K., Morken, M.A., Narisu, N., Nilsson, P., Owen, K.R., Payne, F., Petersen, A.K., Platou, C., Proença, C., Prokopenko, I., Rathmann, W., Rayner, N.W., Robertson, N.R., Rocheleau, G., Roden, M., Sampson, M.J., Saxena, R., Shields, B.M., Shrader, P., Sigurdsson, G., Sparsø, T., Strassburger, K., Stringham, H.M., Sun, Q., Swift, A.J., Thorand, B., Tichet, J., Tuomi, T., van Dam, R.M., van Haeften, T.W., van Herpt, T., van Vliet-Ostaptchouk, J.V., Walters, G.B., Weedon, M.N., Wijmenga, C., Witteman, J., Bergman, R.N., Cauchi, S., Collins, F.S., Gloyn, A.L., Gyllensten, U., Hansen, T., Hide, W.A., Hitman, G.A., Hofman, A., Hunter, D.J., Hveem, K., Laakso, M., Morris, A.D., Palmer, C.N., Rudan, I., Sijbrands, E., Stein, L.D., Tuomilehto, J., Uitterlinden, A., Walker, M., Watanabe, R.M., Abecasis, G.R., Boehm, B.O., Campbell, H., Daly, M.J., Hattersley, A.T., Pedersen, O., Barroso, I., Groop, L., Sladek, R., Thorsteinsdottir, U., Wilson, J.F., Illig, T., Froguel, P., van Duijn, C.M., Stefansson, K., Altshuler, D., Boehnke, M., McCarthy, M.I., Soranzo, N., Wheeler, E., Glazer, N.L., Bouatia-Naji, N., Mägi, R., Randall, J., Elliott, P., Rybin, D., Dehghan, A., Hottenga, J.J., Song, K., Goel, A., Lajunen, T., Doney, A., Cavalcanti-Proença, C., Kumari, M., Timpson, N.J., Zabena, C., Ingelsson, E., An, P., O'Connell, J., Luan, J., Elliott, A., Roccasecca, R.M., Pattou, F., Sethupathy, P., Ariyurek, Y., Barter, P., Beilby, J.P., Ben-Shlomo, Y., Bergmann, S., Bochud, M., Bonnefond, A., Borch-Johnsen, K., Böttcher, Y., Brunner, E., Bumpstead, S.J., Chen, Y.D., Chines, P., Clarke, R., Coin, L.J., Cooper, M.N., Crisponi, L., Day, I.N., de Geus, E.J., Delplanque, J., Fedson, A.C., Fischer-Rosinsky, A., Forouhi, N.G., Franzosi, M.G., Galan, P., Goodarzi, M.O., Graessler, J., Grundy, S., Gwilliam, R., Hallmans, G., Hammond, N., Han, X., Hartikainen, A.L., Hayward, C., Heath, S.C., Hercberg, S., Hillman, D.R., Hingorani, A.D., Hui, J., Hung, J., Kaakinen, M., Kaprio, J., Kesaniemi, Y.A., Kivimaki, M., Knight, B., Koskinen, S., Kovacs, P., Kyvik, K.O., Lathrop, G.M., Lawlor, D.A., Le Bacquer, O., Lecoeur, C., Li, Y., Mahley, R., Mangino, M., Martínez-Larrad, M.T., McAteer, J.B., McPherson, R., Meisinger, C., Melzer, D., Meyre, D., Mitchell, B.D., Mukherjee, S., Naitza, S., Neville, M.J., Orrù, M., Pakyz, R., Paolisso, G., Pattaro, C., Pearson, D., Peden, J.F., Pedersen, N.L., Pfeiffer, A.F., Pichler, I., Polasek, O., Posthuma, D., Potter, S.C., Pouta, A., Province, M.A., Rice, K., Ripatti, S., Rivadeneira, F., Rolandsson, O., Sandbaek, A., Sandhu, M., Sanna, S., Sayer, A.A., Scheet, P., Seedorf, U., Sharp, S.J., Shields, B., Sigurðsson, G., Sijbrands, E.J., Silveira, A., Simpson, L., Singleton, A., Smith, N.L., Sovio, U., Swift, A., Syddall, H., Syvänen, A.C., Tönjes, A., Uitterlinden, A.G., van Dijk, K.W., Varma, D., Visvikis-Siest, S., Vitart, V., Vogelzangs, N., Waeber, G., Wagner, P.J., Walley, A., Ward, K.L., Watkins, H., Wild, S.H., Willemsen, G., Witteman, J.C., Yarnell, J.W., Zelenika, D., Zethelius, B., Zhai, G., Zhao, J.H., Zillikens, M.C., Borecki, I.B., Meneton, P., Magnusson, P.K., Nathan, D.M., Williams, G.H., Silander, K., Bornstein, S.R., Schwarz, P., Spranger, J., Karpe, F., Shuldiner, A.R., Cooper, C., Serrano-Ríos, M., Lind, L., Palmer, L.J., Franks, P.W., Ebrahim, S., Marmot, M., Wright, A.F., Stumvoll, M., Hamsten, A., Buchanan, T.A., Valle, T.T., Rotter, J.I., Penninx, B.W., Boomsma, D.I., Cao, A., Scuteri, A., Schlessinger, D., Uda, M., Ruokonen, A., Jarvelin, M.R., Peltonen, L., Mooser, V., Musunuru, K., Smith, A.V., Edmondson, A.C., Stylianou, I.M., Koseki, M., Pirruccello, J.P., Chasman, D.I., Johansen, C.T., Fouchier, S.W., Peloso, G.M., Barbalic, M., Ricketts, S.L., Bis, J.C., Feitosa, M.F., Orho-Melander, M., Melander, O., Li, X., Cho, Y.S., Go, M.J., Kim, Y.J., Lee, J.Y., Park, T., Kim, K., Sim, X., Ong, R.T., Croteau-Chonka, D.C., Lange, L.A., Smith, J.D., Ziegler, A., Zhang, W., Zee, R.Y., Whitfield, J.B., Thompson, J.R., Surakka, I., Smit, J.H., Sinisalo, J., Scott, J., Saharinen, J., Sabatti, C., Rose, L.M., Roberts, R., Rieder, M., Parker, A.N., Pare, G., O'Donnell, C.J., Nieminen, M.S., Nickerson, D.A., Montgomery, G.W., McArdle, W., Masson, D., Martin, N.G., Marroni, F., Lucas, G., Luben, R., Lokki, M.L., Lettre, G., Launer, L.J., Lakatta, E.G., Laaksonen, R., König, I.R., Khaw, K.T., Kaplan, L.M., Johansson, Å., Janssens, A.C., Igl, W., Hovingh, G.K., Hengstenberg, C., Havulinna, A.S., Hastie, N.D., Harris, T.B., Haritunians, T., Hall, A.S., Groop, L.C., Gonzalez, E., Freimer, N.B., Erdmann, J., Ejebe, K.G., Döring, A., Dominiczak, A.F., Demissie, S., de Faire, U., Caulfield, M.J., Boekholdt, S.M., Assimes, T.L., Quertermous, T., Seielstad, M., Wong, T.Y., Tai, E.S., Feranil, A.B., Kuzawa, C.W., Taylor, H.A., Gabriel, S.B., Holm, H., Gudnason, V., Krauss, R.M., Ordovas, J.M., Munroe, P.B., Kooner, J.S., Tall, A.R., Hegele, R.A., Kastelein, J.J., Schadt, E.E., Strachan, D.P., Reilly, M.P., Samani, N.J., Schunkert, H., Cupples, L.A., Sandhu, M.S., Ridker, P.M., Rader, D.J., and Kathiresan, S.

Abstract

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 = 4.5×10(-8)-1.2×10(-43)). 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<3×10(-4)). 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 = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Published
2012

41. Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.

Author

GIANT Consortium, MAGIC Consortium, GLGC Consortium, Dupuis, J., Langenberg, C., Prokopenko, I., Saxena, R., Soranzo, N., Jackson, AU., Wheeler, E., Glazer, NL., Bouatia-Naji, N., Gloyn, AL., Lindgren, CM., Mägi, R., Morris, AP., Randall, J., Johnson, T., Elliott, P., Rybin, D., Thorleifsson, G., Steinthorsdottir, V., Henneman, P., Grallert, H., Dehghan, A., Hottenga, JJ., Franklin, CS., Navarro, P., Song, K., Goel, A., Perry, JR., Egan, JM., Lajunen, T., Grarup, N., Sparsø, T., Doney, A., Voight, BF., Stringham, HM., Li, M., Kanoni, S., Shrader, P., Cavalcanti-Proença, C., Kumari, M., Qi, L., Timpson, NJ., Gieger, C., Zabena, C., Rocheleau, G., Ingelsson, E., An, P., O'Connell, J., Luan£££Jian'an£££ J., Elliott, A., McCarroll, SA., Payne, F., Roccasecca, RM., Pattou, F., Sethupathy, P., Ardlie, K., Ariyurek, Y., Balkau, B., Barter, P., Beilby, JP., Ben-Shlomo, Y., Benediktsson, R., Bennett, AJ., Bergmann, S., Bochud, M., Boerwinkle, E., Bonnefond, A., Bonnycastle, LL., Borch-Johnsen, K., Böttcher, Y., Brunner, E., Bumpstead, SJ., Charpentier, G., Chen, YD., Chines, P., Clarke, R., Coin, LJ., Cooper, MN., Cornelis, M., Crawford, G., Crisponi, L., Day, IN., de Geus EJ., Delplanque, J., Dina, C., Erdos, MR., Fedson, AC., Fischer-Rosinsky, A., Forouhi, NG., Fox, CS., Frants, R., Franzosi, MG., Galan, P., Goodarzi, MO., Graessler, J., Groves, CJ., Grundy, S., Gwilliam, R., Gyllensten, U., Hadjadj, S., Hallmans, G., Hammond, N., Han, X., Hartikainen, AL., Hassanali, N., Hayward, C., Heath, SC., Hercberg, S., Herder, C., Hicks, AA., Hillman, DR., Hingorani, AD., Hofman, A., Hui, J., Hung, J., Isomaa, B., Johnson, PR., Jørgensen, T., Jula, A., Kaakinen, M., Kaprio, J., Kesaniemi, YA., Kivimaki, M., Knight, B., Koskinen, S., Kovacs, P., Kyvik, KO., Lathrop, GM., Lawlor, DA., Le Bacquer, O., Lecoeur, C., Li, Y., Lyssenko, V., Mahley, R., Mangino, M., Manning, AK., Martínez-Larrad£££María Teresa£££ MT., McAteer, JB., McCulloch, LJ., McPherson, R., Meisinger, C., Melzer, D., Meyre, D., Mitchell, BD., Morken, MA., Mukherjee, S., Naitza, S., Narisu, N., Neville, MJ., Oostra, BA., Orrù, M., Pakyz, R., Palmer, CN., Paolisso, G., Pattaro, C., Pearson, D., Peden, JF., Pedersen, NL., Perola, M., Pfeiffer, AF., Pichler, I., Polasek, O., Posthuma, D., Potter, SC., Pouta, A., Province, MA., Psaty, BM., Rathmann, W., Rayner, NW., Rice, K., Ripatti, S., Rivadeneira, F., Roden, M., Rolandsson, O., Sandbaek, A., Sandhu, M., Sanna, S., Sayer, AA., Scheet, P., Scott, LJ., Seedorf, U., Sharp, SJ., Shields, B., Sigurðsson, G., Sijbrands, EJ., Silveira, A., Simpson, L., Singleton, A., Smith, NL., Sovio, U., Swift, A., Syddall, H., Syvänen, AC., Tanaka, T., Thorand, B., Tichet, J., Tönjes, A., Tuomi, T., Uitterlinden, AG., van Dijk KW., van Hoek, M., Varma, D., Visvikis-Siest, S., Vitart, V., Vogelzangs, N., Waeber, G., Wagner, PJ., Walley, A., Walters, GB., Ward, KL., Watkins, H., Weedon, MN., Wild, SH., Willemsen, G., Witteman, JC., Yarnell, JW., Zeggini, E., Zelenika, D., Zethelius, B., Zhai, G., Zhao, JH., Zillikens, MC., Borecki, IB., Loos, RJ., Meneton, P., Magnusson, PK., Nathan, DM., Williams, GH., Hattersley, AT., Silander, K., Salomaa, V., Smith, GD., Bornstein, SR., Schwarz, P., Spranger, J., Karpe, F., Shuldiner, AR., Cooper, C., Dedoussis, GV., Serrano-Ríos, M., Morris, AD., Lind, L., Palmer, LJ., Hu, FB., Franks, PW., Ebrahim, S., Marmot, M., Kao, WH., Pankow, JS., Sampson, MJ., Kuusisto, J., Laakso, M., Hansen, T., Pedersen, O., Pramstaller, PP., Wichmann, HE., Illig, T., Rudan, I., Wright, AF., Stumvoll, M., Campbell, H., Wilson, JF., Hamsten, A., Bergman, RN., Buchanan, TA., Collins, FS., Mohlke, KL., Tuomilehto, J., Valle, TT., Altshuler, D., Rotter, JI., Siscovick, DS., Penninx, BW., Boomsma, ID., Deloukas, P., Spector, TD., Frayling, TM., Ferrucci, L., Kong, A., Thorsteinsdottir, U., Stefansson, K., van Duijn CM., Aulchenko, YS., Cao, A., Scuteri, A., Schlessinger, D., Uda, M., Ruokonen, A., Jarvelin, MR., Waterworth, DM., Vollenweider, P., Peltonen, L., Mooser, V., Abecasis, RG., Wareham, NJ., Sladek, R., Froguel, P., Watanabe, RM., Meigs, JB., Groop, L., Boehnke, M., McCarthy, MI., Florez, JC., Barroso£££Inês£££ I., Fox, C.S., Liu, Y., White, C.C., Feitosa, M., Smith, A.V., Heard-Costa, N., Lohman, K., Johnson, A.D., Foster, M.C., Greenawalt, D.M., Griffin, P., Ding, J., Newman, A.B., Tylavsky, F., Miljkovic, I., Kritchevsky, S.B., Launer, L., Garcia, M., Eiriksdottir, G., Carr, J.J., Gudnason, V., Harris, T.B., Cupples, L.A., Borecki, I.B., GIANT Consortium, MAGIC Consortium, GLGC Consortium, Dupuis, J., Langenberg, C., Prokopenko, I., Saxena, R., Soranzo, N., Jackson, AU., Wheeler, E., Glazer, NL., Bouatia-Naji, N., Gloyn, AL., Lindgren, CM., Mägi, R., Morris, AP., Randall, J., Johnson, T., Elliott, P., Rybin, D., Thorleifsson, G., Steinthorsdottir, V., Henneman, P., Grallert, H., Dehghan, A., Hottenga, JJ., Franklin, CS., Navarro, P., Song, K., Goel, A., Perry, JR., Egan, JM., Lajunen, T., Grarup, N., Sparsø, T., Doney, A., Voight, BF., Stringham, HM., Li, M., Kanoni, S., Shrader, P., Cavalcanti-Proença, C., Kumari, M., Qi, L., Timpson, NJ., Gieger, C., Zabena, C., Rocheleau, G., Ingelsson, E., An, P., O'Connell, J., Luan£££Jian'an£££ J., Elliott, A., McCarroll, SA., Payne, F., Roccasecca, RM., Pattou, F., Sethupathy, P., Ardlie, K., Ariyurek, Y., Balkau, B., Barter, P., Beilby, JP., Ben-Shlomo, Y., Benediktsson, R., Bennett, AJ., Bergmann, S., Bochud, M., Boerwinkle, E., Bonnefond, A., Bonnycastle, LL., Borch-Johnsen, K., Böttcher, Y., Brunner, E., Bumpstead, SJ., Charpentier, G., Chen, YD., Chines, P., Clarke, R., Coin, LJ., Cooper, MN., Cornelis, M., Crawford, G., Crisponi, L., Day, IN., de Geus EJ., Delplanque, J., Dina, C., Erdos, MR., Fedson, AC., Fischer-Rosinsky, A., Forouhi, NG., Fox, CS., Frants, R., Franzosi, MG., Galan, P., Goodarzi, MO., Graessler, J., Groves, CJ., Grundy, S., Gwilliam, R., Gyllensten, U., Hadjadj, S., Hallmans, G., Hammond, N., Han, X., Hartikainen, AL., Hassanali, N., Hayward, C., Heath, SC., Hercberg, S., Herder, C., Hicks, AA., Hillman, DR., Hingorani, AD., Hofman, A., Hui, J., Hung, J., Isomaa, B., Johnson, PR., Jørgensen, T., Jula, A., Kaakinen, M., Kaprio, J., Kesaniemi, YA., Kivimaki, M., Knight, B., Koskinen, S., Kovacs, P., Kyvik, KO., Lathrop, GM., Lawlor, DA., Le Bacquer, O., Lecoeur, C., Li, Y., Lyssenko, V., Mahley, R., Mangino, M., Manning, AK., Martínez-Larrad£££María Teresa£££ MT., McAteer, JB., McCulloch, LJ., McPherson, R., Meisinger, C., Melzer, D., Meyre, D., Mitchell, BD., Morken, MA., Mukherjee, S., Naitza, S., Narisu, N., Neville, MJ., Oostra, BA., Orrù, M., Pakyz, R., Palmer, CN., Paolisso, G., Pattaro, C., Pearson, D., Peden, JF., Pedersen, NL., Perola, M., Pfeiffer, AF., Pichler, I., Polasek, O., Posthuma, D., Potter, SC., Pouta, A., Province, MA., Psaty, BM., Rathmann, W., Rayner, NW., Rice, K., Ripatti, S., Rivadeneira, F., Roden, M., Rolandsson, O., Sandbaek, A., Sandhu, M., Sanna, S., Sayer, AA., Scheet, P., Scott, LJ., Seedorf, U., Sharp, SJ., Shields, B., Sigurðsson, G., Sijbrands, EJ., Silveira, A., Simpson, L., Singleton, A., Smith, NL., Sovio, U., Swift, A., Syddall, H., Syvänen, AC., Tanaka, T., Thorand, B., Tichet, J., Tönjes, A., Tuomi, T., Uitterlinden, AG., van Dijk KW., van Hoek, M., Varma, D., Visvikis-Siest, S., Vitart, V., Vogelzangs, N., Waeber, G., Wagner, PJ., Walley, A., Walters, GB., Ward, KL., Watkins, H., Weedon, MN., Wild, SH., Willemsen, G., Witteman, JC., Yarnell, JW., Zeggini, E., Zelenika, D., Zethelius, B., Zhai, G., Zhao, JH., Zillikens, MC., Borecki, IB., Loos, RJ., Meneton, P., Magnusson, PK., Nathan, DM., Williams, GH., Hattersley, AT., Silander, K., Salomaa, V., Smith, GD., Bornstein, SR., Schwarz, P., Spranger, J., Karpe, F., Shuldiner, AR., Cooper, C., Dedoussis, GV., Serrano-Ríos, M., Morris, AD., Lind, L., Palmer, LJ., Hu, FB., Franks, PW., Ebrahim, S., Marmot, M., Kao, WH., Pankow, JS., Sampson, MJ., Kuusisto, J., Laakso, M., Hansen, T., Pedersen, O., Pramstaller, PP., Wichmann, HE., Illig, T., Rudan, I., Wright, AF., Stumvoll, M., Campbell, H., Wilson, JF., Hamsten, A., Bergman, RN., Buchanan, TA., Collins, FS., Mohlke, KL., Tuomilehto, J., Valle, TT., Altshuler, D., Rotter, JI., Siscovick, DS., Penninx, BW., Boomsma, ID., Deloukas, P., Spector, TD., Frayling, TM., Ferrucci, L., Kong, A., Thorsteinsdottir, U., Stefansson, K., van Duijn CM., Aulchenko, YS., Cao, A., Scuteri, A., Schlessinger, D., Uda, M., Ruokonen, A., Jarvelin, MR., Waterworth, DM., Vollenweider, P., Peltonen, L., Mooser, V., Abecasis, RG., Wareham, NJ., Sladek, R., Froguel, P., Watanabe, RM., Meigs, JB., Groop, L., Boehnke, M., McCarthy, MI., Florez, JC., Barroso£££Inês£££ I., Fox, C.S., Liu, Y., White, C.C., Feitosa, M., Smith, A.V., Heard-Costa, N., Lohman, K., Johnson, A.D., Foster, M.C., Greenawalt, D.M., Griffin, P., Ding, J., Newman, A.B., Tylavsky, F., Miljkovic, I., Kritchevsky, S.B., Launer, L., Garcia, M., Eiriksdottir, G., Carr, J.J., Gudnason, V., Harris, T.B., Cupples, L.A., and Borecki, I.B.

Abstract

Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1 × 10E-09), previously identified in association with waist-hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9 × 10E-08). Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]). Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist-hip ratio adjusted for BMI); associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a SNP for VAT in

Published
2012

42. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

Author

Strawbridge, R.J. Dupuis, J. Prokopenko, I. Barker, A. Ahlqvist, E. Rybin, D. Petrie, J.R. Travers, M.E. Bouatia-Naji, N. Dimas, A.S. Nica, A.C. Wheeler, E. Chen, H. Voight, B.F. Taneera, J. Kanoni, S. Peden, J.F. Turrini, F. Gustafsson, S. Zabena, C. Almgren, P. Barker, D.J.P. Barnes, D. Dennison, E.M. Eriksson, J.G. Eriksson, P. Eury, E. Folkersen, L. Fox, C.S. Frayling, T.M. Goel, A. Gu, H.F. Horikoshi, M. Isomaa, B. Jackson, A.U. Jameson, K.A. Kajantie, E. Kerr-Conte, J. Kuulasmaa, T. Kuusisto, J. Loos, R.J.F. Luan, J. Makrilakis, K. Manning, A.K. Martínez-Larrad, M.T. Narisu, N. Mannila, M.N. Öhrvik, J. Osmond, C. Pascoe, L. Payne, F. Sayer, A.A. Sennblad, B. Silveira, A. Stančcáková, A. Stirrups, K. Swift, A.J. Syvänen, A.-C. Tuomi, T. Van't Hooft, F.M. Walker, M. Weedon, M.N. Xie, W. Zethelius, B. Scott, L.J. Steinthorsdottir, V. Morris, A.P. Dina, C. Welch, R.P. Zeggini, E. Huth, C. Aulchenko, Y.S. Thorleifsson, G. Mcculloch, L.J. Ferreira, T. Grallert, H. Amin, N. Wu, G. Willer, C.J. Raychaudhuri, S. McCarroll, S.A. Hofmann, O.M. Qi, L. Segre, A.V. Van Hoek, M. Navarro, P. Ardlie, K. Balkau, B. Benediktsson, R. Bennett, A.J. Blagieva, R. Boerwinkle, E. Bonnycastle, L.L. Bostrom, K.B. Bravenboer, B. Bumpstead, S. Burtt, N.P. Charpentier, G. Chines, P.S. Cornelis, M. Couper, D.J. Crawford, G. Doney, A.S.F. Elliott, K.S. Elliott, A.L. Erdos, M.R. Franklin, C.S. Ganser, M. Gieger, C. Grarup, N. Green, T. Griffin, S. Groves, C.J. Guiducci, C. Hadjadj, S. Hassanali, N. Herder, C. Johnson, P.R.V. Jorgensen, T. Kao, W.H.L. Klopp, N. Kong, A. Kraft, P. Lauritzen, T. Li, M. Lieverse, A. Lindgren, C.M. Lyssenko, V. Marre, M. Meitinger, T. Midthjell, K. Morken, M.A. Nilsson, P. Owen, K.R. Perry, J.R.B. Petersen, A.-K. Platou, C. Proenca, C. Rathmann, W. Rayner, N.W. Robertson, N.R. Rocheleau, G. Roden, M. Sampson, M.J. Saxena, R. Shields, B.M. Shrader, P. Sigurdsson, G. Sparso, T. Strassburger, K. Stringham, H.M. Sun, Q. Thorand, B. Tichet, J. Van Dam, R.M. Van Ha and Strawbridge, R.J. Dupuis, J. Prokopenko, I. Barker, A. Ahlqvist, E. Rybin, D. Petrie, J.R. Travers, M.E. Bouatia-Naji, N. Dimas, A.S. Nica, A.C. Wheeler, E. Chen, H. Voight, B.F. Taneera, J. Kanoni, S. Peden, J.F. Turrini, F. Gustafsson, S. Zabena, C. Almgren, P. Barker, D.J.P. Barnes, D. Dennison, E.M. Eriksson, J.G. Eriksson, P. Eury, E. Folkersen, L. Fox, C.S. Frayling, T.M. Goel, A. Gu, H.F. Horikoshi, M. Isomaa, B. Jackson, A.U. Jameson, K.A. Kajantie, E. Kerr-Conte, J. Kuulasmaa, T. Kuusisto, J. Loos, R.J.F. Luan, J. Makrilakis, K. Manning, A.K. Martínez-Larrad, M.T. Narisu, N. Mannila, M.N. Öhrvik, J. Osmond, C. Pascoe, L. Payne, F. Sayer, A.A. Sennblad, B. Silveira, A. Stančcáková, A. Stirrups, K. Swift, A.J. Syvänen, A.-C. Tuomi, T. Van't Hooft, F.M. Walker, M. Weedon, M.N. Xie, W. Zethelius, B. Scott, L.J. Steinthorsdottir, V. Morris, A.P. Dina, C. Welch, R.P. Zeggini, E. Huth, C. Aulchenko, Y.S. Thorleifsson, G. Mcculloch, L.J. Ferreira, T. Grallert, H. Amin, N. Wu, G. Willer, C.J. Raychaudhuri, S. McCarroll, S.A. Hofmann, O.M. Qi, L. Segre, A.V. Van Hoek, M. Navarro, P. Ardlie, K. Balkau, B. Benediktsson, R. Bennett, A.J. Blagieva, R. Boerwinkle, E. Bonnycastle, L.L. Bostrom, K.B. Bravenboer, B. Bumpstead, S. Burtt, N.P. Charpentier, G. Chines, P.S. Cornelis, M. Couper, D.J. Crawford, G. Doney, A.S.F. Elliott, K.S. Elliott, A.L. Erdos, M.R. Franklin, C.S. Ganser, M. Gieger, C. Grarup, N. Green, T. Griffin, S. Groves, C.J. Guiducci, C. Hadjadj, S. Hassanali, N. Herder, C. Johnson, P.R.V. Jorgensen, T. Kao, W.H.L. Klopp, N. Kong, A. Kraft, P. Lauritzen, T. Li, M. Lieverse, A. Lindgren, C.M. Lyssenko, V. Marre, M. Meitinger, T. Midthjell, K. Morken, M.A. Nilsson, P. Owen, K.R. Perry, J.R.B. Petersen, A.-K. Platou, C. Proenca, C. Rathmann, W. Rayner, N.W. Robertson, N.R. Rocheleau, G. Roden, M. Sampson, M.J. Saxena, R. Shields, B.M. Shrader, P. Sigurdsson, G. Sparso, T. Strassburger, K. Stringham, H.M. Sun, Q. Thorand, B. Tichet, J. Van Dam, R.M. Van Ha

Abstract

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 × 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. © 2011 by the American Diabetes Association.

Published
2011

43. Management of urban development: Example of the transformation of two Dutch former port areas

Author

Van Hoek, M. (author), Wigmans, G. (author), Van Hoek, M. (author), and Wigmans, G. (author)

Abstract

The more traditional approach of developing cities through government lead town planning has been gradually shifting to a more entrepreneurial approach of strategic management of both public and private initiatives in the urban environment. This approach combines aspects of governance, urban planning, economic development, financial management, social planning and marketing and leads to a more integrated strategic decision making process in which both public and private sector are involved. It is the task of urban management to improve the attractiveness of the city and its relative competitive position by developing and implementing an integrated strategy. This integrated strategy can be seen as a way to realise the objective of strengthening the economical, social and cultural situation of the urban region, which, in its turn, can be reached by taking into account all relevant factors that can influence the development process. The ability to develop and implement an integral urban development vision largely depends on achieving sufficient organising capacity. This organising capacity indicates the organisational possibilities that an urban region possess in order to be able to develop and implement an integral strategy. Organising capacity is the ability to enlist all actors involved, and with their help generate new ideas and develop and implement a policy designed to respond to fundamental developments and create conditions for sustainable economic growth.An important aspect of modern urban management is city marketing. In city marketing attention is focused on the urban functions and their target groups: the potential users of these functions. In urban management, on the contrary, stakeholders have a key position. City marketing and urban management can be seen as the‘ invisible hand’ of market coordination versus the‘ visible hand’ of government regulation. This implies that co-ordination and regulation can be considered as decentralised tasks of urban manage, Real Estate and Housing, Architecture

Published
2011

46. Erratum: Corrigendum: Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Author

Voight, BF, Scott, LJ, Steinthorsdottir, V, Morris, AP, Dina, C, Welch, RP, Zeggini, E, Huth, C, Aulchenko, YS, Thorleifsson, G, McCulloch, LJ, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, CJ, Raychaudhuri, S, McCarroll, SA, Langenberg, C, Hofmann, OM, Dupuis, J, Qi, L, Segrè, AV, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, AJ, Blagieva, R, Boerwinkle, E, Bonnycastle, LL, Boström, KB, Bravenboer, B, Bumpstead, S, Burtt, NP, Charpentier, G, Chines, PS, Cornelis, M, Couper, DJ, Crawford, G, Doney, AS, Elliott, KS, Elliott, AL, Erdos, MR, Fox, CS, Franklin, CS, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, CJ, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, AU, Johnson, PR, Jørgensen, T, Kao, WH, Klopp, N, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, CM, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, MA, Narisu, N, Nilsson, P, Owen, KR, Payne, F, Perry, JR, Petersen, AK, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, Rayner, NW, Robertson, NR, Rocheleau, G, Roden, M, Sampson, MJ, Saxena, R, Shields, BM, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, HM, Sun, Q, Swift, AJ, Thorand, B, Tichet, J, Tuomi, T, van Dam, RM, van Haeften, TW, van Herpt, T, van Vliet-Ostaptchouk, JV, Walters, GB, Weedon, MN, Wijmenga, C, Witteman, J, Bergman, RN, Cauchi, S, Collins, FS, Gloyn, AL, Gyllensten, U, Hansen, T, Hide, WA, Hitman, GA, Hofman, A, Hunter, DJ, Hveem, K, Laakso, M, Mohlke, KL, Morris, AD, Palmer, CN, Pramstaller, PP, Rudan, I, Sijbrands, E, Stein, LD, Tuomilehto, J, Uitterlinden, A, Walker, M, Wareham, NJ, Watanabe, RM, Abecasis, GR, Boehm, BO, Campbell, H, Daly, MJ, Hattersley, AT, Hu, FB, Meigs, JB, Pankow, JS, Pedersen, O, Wichmann, HE, Barroso, I, Florez, JC, Frayling, TM, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, JF, Illig, T, Froguel, P, van Duijn, CM, Stefansson, K, Altshuler, D, Boehnke, M, and McCarthy, MI

Subjects
Genetics, Scale (ratio), medicine, Susceptibility locus, Type 2 diabetes, Biology, medicine.disease, Genetic association
Published
2011
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