Author: "Meulenbelt, I. (Ingrid)" / Search Limiters: Full Text - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Meulenbelt, I. (Ingrid)"' showing total 23 results

Start Over Author "Meulenbelt, I. (Ingrid)" Search Limiters Full Text

23 results on '"Meulenbelt, I. (Ingrid)"'

1. Serum fatty acid chain length associates with prevalent symptomatic end-stage osteoarthritis, independent of BMI

Author: Meessen, J.M.T.A., Saberi-Hosnijeh, F., Bomer, N. (Nils), den Hollander, W, Bom, J.G., van Hilten, J.A., Spil, W.E. (Willem) van, So-Osman, C. (Cynthia), Uitterlinden, A.G. (André), Kloppenburg, M. (Margreet), Nelissen, R.G.H.H. (Rob), Duijn, C.M., Slagboom, PE, Meurs, J.B.J. (Joyce) van, Meulenbelt, I. (Ingrid), Meessen, J.M.T.A., Saberi-Hosnijeh, F., Bomer, N. (Nils), den Hollander, W, Bom, J.G., van Hilten, J.A., Spil, W.E. (Willem) van, So-Osman, C. (Cynthia), Uitterlinden, A.G. (André), Kloppenburg, M. (Margreet), Nelissen, R.G.H.H. (Rob), Duijn, C.M., Slagboom, PE, Meurs, J.B.J. (Joyce) van, and Meulenbelt, I. (Ingrid)
Published: 2020
Full Text: View/download PDF

2. Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation

Author: Teumer, A. (Alexander), Chaker, L. (Layal), Groeneweg, S. (Stefan), Li, Y. (Yong), Di Munno, C. (Celia), Barbieri, C. (Caterina), Schultheiss, U.T. (Ulla T.), Traglia, M. (Michela), Ahluwalia, T.S. (Tarunveer Singh), Akiyama, M. (Masato), Appel, E.V.R. (Emil Vincent R.), Arking, D.E. (Dan), Arnold, A.M. (Alice), Astrup, A. (Arne), Beekman, M. (Marian), Beilby, J.P. (John), Bekaert, S. (Sofie), Boerwinkle, E. (Eric), Brown, S.J. (Stephen), Buyzere, M. (Marc) de, Campbell, P.J. (Purdey J.), Ceresini, G. (Graziano), Cerqueira, C. (Charlotte), Cucca, F. (Francesco), Deary, I.J. (Ian), Deelen, J. (Joris), Eckardt, K.-U. (Kai-Uwe), Ekici, A.B. (Arif B.), Hagen, K. (Knut), Ferrrucci, L. (Luigi), Fiers, T. (Tom), Fiorillo, E. (Edoardo), Ford, I. (Ian), Fox, C.S. (Caroline), Fuchsberger, C. (Christian), Galesloot, T.E. (Tessel), Gieger, C. (Christian), Gögele, M. (Martin), Grandi, A. (Alessandro) de, Grarup, N. (Niels), Greiser, K.H. (Karin Halina), Haljas, K. (Kadri), Hansen, T. (Torben), Harris, S.E. (Sarah), Heemst, D. (Diana) van, Heijer, M. (Martin) den, Hicks, A.A. (Andrew A.), Hollander, W. (Wouter) den, Homuth, G. (Georg), Hui, J. (Jennie), Ikram, M.A. (Arfan), Ittermann, T. (Till), Jensen, R.A. (Richard A.), Jing, J. (Jiaojiao), Jukema, J.W. (Jan Wouter), Kajantie, E. (Eero), Kamatani, Y. (Yoichiro), Kasbohm, E. (Elisa), Kaufman, J.-M. (Jean-Marc), Kiemeney, L.A. (Lambertus A.), Kloppenburg, M. (Margreet), Kronenberg, F. (Florian), Kubo, M. (Michiaki), Lahti, J. (Jari), Lapauw, B. (Bruno), Li, S. (Shuo), Liewald, D.C.M. (David C. M.), Alizadeh, B.Z. (Behrooz), Boezen, H.M. (Marike), Franke, L. (Lude), van der Harst, P. (Pim), Navis, G. (Gerjan), Rots, M.G. (M.), Snieder, H. (Harold), Swertz, M.A. (Morris A.), Wijmenga, C. (Cisca), Lim, E.M. (Ee Mun), Linneberg, A. (Allan), Marina, M. (Michela), Mascalzoni, D. (Deborah), Matsuda, K. (Koichi), Medenwald, D. (Daniel), Meisinger, C. (Christa), Meulenbelt, I. (Ingrid), Meyer, T. (Thorsten), Meyer zu Schwabedissen, H.E. (Henriette E.), Mikolajczyk, R. (Rafael), Moed, H. (Heleen), Netea-Maier, R.T. (Romana), Nolte, I.M. (Ilja), Okada, Y. (Yukinori), Pala, M. (Mauro), Penninx, B.W.J.H., Pedersen, O. (Oluf), Petersmann, A. (Astrid), Porcu, E. (Eleonora), Postmus, D. (Douwe), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Ramos, Y.F.M. (Yolande F. M.), Rawal, R. (Rajesh), Redmond, P. (Paul), Richards, J.B. (Brent), Rietzschel, E.R. (Ernst), Rivadeneira Ramirez, F. (Fernando), Roef, G.L. (Greet), Rotter, J.I. (Jerome I.), Sala, C. (Cinzia), Schlessinger, D. (David), Selvin, E. (Elizabeth), Slagboom, P.E. (Eline), Soranzo, N. (Nicole), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Starr, J.M. (John), Stott, D.J. (David. J.), Taes, Y.E. (Youri), Taliun, D. (Daniel), Tanaka, T. (Toshiko), Thuesen, L. (Leif), Tiller, D. (Daniel), Toniolo, D. (Daniela), Uitterlinden, A.G. (Andre G.), Visser, W.E. (Edward), Walsh, J.P. (John P.), Wilson, S.G. (Scott), Wolffenbuttel, B.H.R. (Bruce), Yang, Q. (Qiong Fang), Zheng, H.-F. (Hou-Feng), Cappola, A.R. (Anne), Peeters, R.P. (Robin), Naitza, S. (Silvia), Völzke, H. (Henry), Sanna, S. (Serena), Köttgen, A. (Anna), Visser, T.J. (Theo), Medici, M. (Marco), Teumer, A. (Alexander), Chaker, L. (Layal), Groeneweg, S. (Stefan), Li, Y. (Yong), Di Munno, C. (Celia), Barbieri, C. (Caterina), Schultheiss, U.T. (Ulla T.), Traglia, M. (Michela), Ahluwalia, T.S. (Tarunveer Singh), Akiyama, M. (Masato), Appel, E.V.R. (Emil Vincent R.), Arking, D.E. (Dan), Arnold, A.M. (Alice), Astrup, A. (Arne), Beekman, M. (Marian), Beilby, J.P. (John), Bekaert, S. (Sofie), Boerwinkle, E. (Eric), Brown, S.J. (Stephen), Buyzere, M. (Marc) de, Campbell, P.J. (Purdey J.), Ceresini, G. (Graziano), Cerqueira, C. (Charlotte), Cucca, F. (Francesco), Deary, I.J. (Ian), Deelen, J. (Joris), Eckardt, K.-U. (Kai-Uwe), Ekici, A.B. (Arif B.), Hagen, K. (Knut), Ferrrucci, L. (Luigi), Fiers, T. (Tom), Fiorillo, E. (Edoardo), Ford, I. (Ian), Fox, C.S. (Caroline), Fuchsberger, C. (Christian), Galesloot, T.E. (Tessel), Gieger, C. (Christian), Gögele, M. (Martin), Grandi, A. (Alessandro) de, Grarup, N. (Niels), Greiser, K.H. (Karin Halina), Haljas, K. (Kadri), Hansen, T. (Torben), Harris, S.E. (Sarah), Heemst, D. (Diana) van, Heijer, M. (Martin) den, Hicks, A.A. (Andrew A.), Hollander, W. (Wouter) den, Homuth, G. (Georg), Hui, J. (Jennie), Ikram, M.A. (Arfan), Ittermann, T. (Till), Jensen, R.A. (Richard A.), Jing, J. (Jiaojiao), Jukema, J.W. (Jan Wouter), Kajantie, E. (Eero), Kamatani, Y. (Yoichiro), Kasbohm, E. (Elisa), Kaufman, J.-M. (Jean-Marc), Kiemeney, L.A. (Lambertus A.), Kloppenburg, M. (Margreet), Kronenberg, F. (Florian), Kubo, M. (Michiaki), Lahti, J. (Jari), Lapauw, B. (Bruno), Li, S. (Shuo), Liewald, D.C.M. (David C. M.), Alizadeh, B.Z. (Behrooz), Boezen, H.M. (Marike), Franke, L. (Lude), van der Harst, P. (Pim), Navis, G. (Gerjan), Rots, M.G. (M.), Snieder, H. (Harold), Swertz, M.A. (Morris A.), Wijmenga, C. (Cisca), Lim, E.M. (Ee Mun), Linneberg, A. (Allan), Marina, M. (Michela), Mascalzoni, D. (Deborah), Matsuda, K. (Koichi), Medenwald, D. (Daniel), Meisinger, C. (Christa), Meulenbelt, I. (Ingrid), Meyer, T. (Thorsten), Meyer zu Schwabedissen, H.E. (Henriette E.), Mikolajczyk, R. (Rafael), Moed, H. (Heleen), Netea-Maier, R.T. (Romana), Nolte, I.M. (Ilja), Okada, Y. (Yukinori), Pala, M. (Mauro), Penninx, B.W.J.H., Pedersen, O. (Oluf), Petersmann, A. (Astrid), Porcu, E. (Eleonora), Postmus, D. (Douwe), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Ramos, Y.F.M. (Yolande F. M.), Rawal, R. (Rajesh), Redmond, P. (Paul), Richards, J.B. (Brent), Rietzschel, E.R. (Ernst), Rivadeneira Ramirez, F. (Fernando), Roef, G.L. (Greet), Rotter, J.I. (Jerome I.), Sala, C. (Cinzia), Schlessinger, D. (David), Selvin, E. (Elizabeth), Slagboom, P.E. (Eline), Soranzo, N. (Nicole), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Starr, J.M. (John), Stott, D.J. (David. J.), Taes, Y.E. (Youri), Taliun, D. (Daniel), Tanaka, T. (Toshiko), Thuesen, L. (Leif), Tiller, D. (Daniel), Toniolo, D. (Daniela), Uitterlinden, A.G. (Andre G.), Visser, W.E. (Edward), Walsh, J.P. (John P.), Wilson, S.G. (Scott), Wolffenbuttel, B.H.R. (Bruce), Yang, Q. (Qiong Fang), Zheng, H.-F. (Hou-Feng), Cappola, A.R. (Anne), Peeters, R.P. (Robin), Naitza, S. (Silvia), Völzke, H. (Henry), Sanna, S. (Serena), Köttgen, A. (Anna), Visser, T.J. (Theo), and Medici, M. (Marco)
Abstract: Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves’ disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets.
Published: 2018
Full Text: View/download PDF

3. Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

Author: Hinney, A. (Anke), Kesselmeier, M. (M.), Jall, S. (S.), Volckmar, A.-L. (A. L.), Föcker, M. (M.), Antel, J. (J.), Heid, I.M. (Iris), Winkler, T.W. (Thomas W.), Grant, S.F.A. (S. F.A.), Guo, Y. (Yongli), Bergen, A.W. (Andrew), Grant, S.F.A. (Struan), Berrettini, W. (Wade), Hakonarson, H. (Hakon), Herpertz-Dahlmann, B. (B.), De Zwaan, M. (M.), Herzog, W. (W.), Ehrlich, S.M. (Stefan), Zipfel, S. (S.), Egberts, K. (Karin), Adan, R. (R.), Brandys, M. (M.), Elburg, A.A. (Annemarie) van, Boraska Perica, V. (V.), Müller, T.D., Tschöp, M.H. (M. H.), Zeggini, E. (Eleftheria), Bulik, C.M. (C. M.), Collier, D.A. (David), Scherag, A. (A.), Hebebrand, J. (J.), Tschop, M. (Matthias), Floyd, J. (Jamie), Thornton, L.M. (Laura), Huckins, L.M. (Laura M), Southam, L. (Lorraine), Rayner, N.W. (Nigel William), Tachmazidou, I. (Ioanna), Klump, K.L. (K. L.), Treasure, J. (Janet), Lewis, C.M. (Cathryn), Schmidt, U. (Ulrike), Tozzi, F. (Federica), Iezebrink, K. (Kirsty), Gorwood, P. (Philip), Kas, M.J.H. (Martien), Favaro, A. (Angela), Santonastaso, P. (Paolo), Fernández-Aranda, F. (Fernando), Gratacos, M. (Monica), Rybakowski, F. (Filip), Dmitrzak-Weglarz, M. (Monika), Kaprio, J. (Jaakko), Keski-Rahkonen, A. (Anna), Raevuori-Helkamaa, A. (Anu), Furth, E.F. (Eric) van, Slof-Op’t Landt, M.C.T. (Margarita C. T.), Hudson, J.I. (James I), Knudsen, G.P.S. (Gun Peggy S.), Monteleone, P. (Palmiero), Kaplan, A.S. (Allan S), Karwautz, A. (Andreas), Li, D. (Dong), Komaki, G. (Gen), Ando, T. (Tetsuya), Inoko, H. (Hidetoshi), Esko, T. (T.), Fischer, K. (Krista), Männik, K. (Katrin), Metspalu, A. (Andres), Baker, J.H. (Jessica H), Cone, R.D. (Roger D), Esko, T. (Tõnu), DeSocio, J.E. (Janiece E), Hilliard, C.E. (Christopher E), O’Toole, J.K. (Julie K), Pantel, J. (Jacques), Szatkiewicz, J.P. (Jin P), Taico, C. (Chrysecolla), Zerwas, S. (Stephanie), Trace, S.E. (Sara E), Davis, O.S.P. (Oliver S.), Helder, S. (Sietske), Bühren, K. (Katharina), Burghardt, R. (Roland), Imgart, H. (Hartmut), Scherag, A. (Andre), Boni, C. (Claudette), Ramoz, N. (Nicolas), Versini, A. (Audrey), Danner, U.N. (Unna N), de Kove, C. (Carolien), Hendriks, J. (Judith), Koeleman, B.P.C. (Bobby P. C.), Ophoff, R.A. (Roel), Strengman, E. (Eric), Bruson, A. (Alice), Clementi, M. (Maurizio), Degortes, D. (Daniela), Forzan, M. (Monica), Tenconi, E. (Elena), Docampo, E. (Elisa), Jiménez-Murcia, G.E.S. (Geòrgia Escaramí Susana), Lissowska, J. (Jolanta), Rajewski, A. (Andrzej), Szeszenia-Dabrowska, N. (Neonila), Slopien, A. (Agnieszka), Hauser, J. (J.), Karhunen, L. (Leila), Meulenbelt, I. (Ingrid), Slagboom, P.E. (Eline), Tortorella, A. (Alfonso), Maj, M. (Mario), Dedoussis, G.V. (George), Dedoussis, G.V. (G. V.), Koeleman, B.P.C. (Bobby), Gonidakis, F. (Fragiskos), Tziouvas, K. (Konstantinos), Tsitsika, A. (Artemis), Papezova, H. (Hana), Slachtova, L. (Lenka), Martaskova, D. (Debora), Kennedy, J.L., Levitan, R.D. (Robert D), Yilmaz, Z. (Zeynep), Huemer, J. (Julia), Koubek, D. (Doris), Merl, E. (Elisabeth), Wagner, G. (Gudrun), Lichtenstein, P. (Paul), Breen, G. (Gerome), Cohen-Woods, S. (Sarah), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Cichon, S. (Sven), Giegling, I. (Ina), Herms, S. (Stefan), Rujescu, D. (Dan), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Sladek, R. (Rob), Gambaro, G. (Giovanni), Soranzo, N. (Nicole), Julia, A. (Antonio), Marsal, S. (Sara), Rabionet, R. (Raquel), Gaborieau, V. (Valerie), Dick, D.M. (Danielle), Palotie, A. (A.), Ripatti, S. (Samuli), Widen, E., Espeseth, T. (Thomas), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Steen, V.M. (Vidar), Le Hellard, S. (Stephanie), Mattingsdal, M. (Morten), Ntalla, I. (Ioanna), Bencko, V. (Vladimir), Foretova, L. (Lenka), Janout, V. (Vladimir), Navratilova, M. (Marie), Pinto, D. (Dalila), Scherer, S.W. (Stephen W), Carlberg, L. (Laura), Schosser, A. (Alexandra), Alfredsson, L. (Lars), Pinto, D. (Duane), Scherer, S.W. (Stephen), Padyukov, L. (Leonid), Finan, C. (Chris), Kalsi, G. (Gursharan), Roberts, M. (Marion), Logan, D.W. (Darren W), Peltonen, L. (Leena Johanna), Ritchie, G.R.S. (Graham R.S.), Barrett, J.C. (Jeffrey), Estivill, X. (Xavier), Sullivan, P.F. (Patrick), Anderson, C.A. (Carl A), McGinnis, R. (Ralph), Sambrook, J. (Jennifer), Stephens, J. (Jonathan), Ouwehand, W.H. (Willem), McArdle, P.F. (P. F.), Ring, S.M. (Susan), Strachan, D.P. (David), Alexander, G. (Graeme), Conlon, P.J. (Peter J), Dominiczak, A. (Anna), Duncanson, A. (Audrey), Padyukov, L. (L.), Langford, C. (Cordelia), Lord, G. (Graham), Conlon, P. (Peter), Sandford, R. (Richard), Sheerin, N. (Neil), Vannberg, F.O. (Frederik O), Blackburn, H. (Hannah), Maxwell, A.P. (A.), Edkins, T. (Ted), Gillman, M.W. (Matthew W.), Gray, E. (Emma), Hunt, S.E. (Sarah E), Nengut, S.-G. (Suna-Gumuscu), Potter, S.C. (Simon), Rich, S.S. (Stephen), Simpkin, D. (Douglas), Whittaker, P. (Pamela), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N. (N.), Benke, K. (K.), Berry, D. (Diane), Boomsma, D.I. (Dorret), Bradfield, J.P. (Jonathan), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cooper, C. (C.), Cousminer, D.L. (Diana), Das, S. (Shikta), Elliott, P. (P.), Evans, D.M. (D. M.), Feenstra, B. (B.), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Freathy, R.M. (Rachel), Gaillard, R. (R.), Geller, F. (Frank), Groen-Blokhuis, M. (Maria), Goh, L.K. (L. K.), Guxens Junyent, M. (Mònica), Hattersley, A.T. (Andrew), Haworth, C.M.A. (Claire M.), Hadley, D. (D.), Heinrich, J. (J.), Hirschhorn, J.N. (Joel), Hocher, B. (Berthold), Holloway, J.W. (J. W.), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (E.), Iñiguez, C. (C.), Jaddoe, V.W. (V. W.), Jarvelin, M.R. (M. R.), Kaakinen, M. (M.), Kilpeläinen, T.O. (Tuomas), Hypponen, E. (Elina), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Cooper, C. (Charles), Lange, L.A. (Leslie), Lawlor, D.A. (D. A.), Lehtimäki, T. (Terho), Lewin, A. (Alex), Elliott, P. (Paul), Lindi, V. (Virpi), Maggi, R. (Reedik), Feenstra, B. (Bjarke), McCarthy, M.I. (M. I.), Melbye, M. (Mads), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (D. O.), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Oken, E. (Emily), Ong, K.K. (K. K.), O'Reilly, P.F. (P. F.), Palmer, C. (Cameron), Panoutsopoulou, K. (K.), Pararajasingham, J. (Jennifer), Pearson, E.R. (E. R.), Pennell, C.E. (Craig), Power, C. (Christopher), Price, T.S. (Thomas), Prokopenko, I. (Inga), Raitakari, O.T. (O. T.), Rodriguez, A. (A.), Salem, R.M. (Rany), Saw, S.M. (S. M.), Sebert, S. (S.), Siitonen, N. (Niina), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Sovio, U. (Ulla), Lawlor, D.A. (Debbie), Sunyer, J. (J.), Taal, H.R. (Rob), Teo, Y.Y. (Y. Y.), Thiering, E. (Elisabeth), Tiesler, C. (C.), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Valcárcel, B. (Beatriz), Teo, Y.Y. (Yik Ying), White, S.J. (Stefan), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (J. F.), Yaghootkar, H. (H.), Elks, C.E. (Cathy), Perry, J.R. (J. R.), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (C.), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (E. M.), Gudbjartsson, D.F. (Daniel), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (P.), Mangino, M. (Massimo), Byrne, E.M. (Enda), Smith, A.V. (Albert), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (J. H.), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Smith, A.V. (Davey), Chanock, S.J. (Stephen), Warrington, M. (M.), Zgaga, L. (L.), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (T.), Ulivi, S. (Shelia), Sunyer, J. (Jordi), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Boerwinkle, E. (E.), Buring, J.E. (Julie), Busonero, F. (F.), Barroso, I.E. (Inês), Chanock, S.J. (S. J.), Warrington, N.M. (Nicole), Couper, D.J. (David), Coviello, A.D. (Andrea), Busonero, F., Faire, U. (Ulf) de, de Geus, E.J. (E. J.), Deloukas, P. (Panagiotis), Döring, A. (Angela), Davey Smith, G. (G.), Adamo, P. (Pio) d', Eiriksdottir, G. (Gudny), Geus, E.J.C. (Eco) de, Hagen, K. (Knut), Ferrucci, L. (L.), Folsom, A.R. (A. R.), Foroud, T. (T.), Garcia, M.E. (M.), Gasparini, P. (P.), Gieger, C. (Christian), Gudnason, V. (V.), Folsom, A.R. (Aaron), Hankinson, S.E. (S. E.), Ferreli, L. (Liana), Gasparini, P. (Paolo), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (F. B.), Illig, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K.T. (K. T.), Kiel, D.P. (Douglas P.), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S. (J. S.), Li, S. (S.), Liu, J. (J.), Levy, D. (D.), Martin, N.G. (N. G.), Aspelund, T. (Thor), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (M.), Ness, A.R. (A. R.), Boerwinkle, E.A. (Eric), Oostra, B.A. (Ben), Peacock, M. (M.), Pare, G. (Guillame), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Cornelis, M. (Marilyn), Polasek, O. (Ozren), Plump, A.S. (A. S.), Peacock, M. (Munro), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Rivadeneira, F. (F.), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (D.), Scuteri, A. (A.), Segrè, A.V. (Ayellet), Foroud, T. (Tatiana), Srinivasan, S.R. (Sathanur), Tammesoo, M.L. (M. L.), Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Scuteri, A. (Angelo), Tryggvadottir, L. (Laufey), Tyrer, J. (J.), Uda, M. (M.), van Dam, R.M. (R. M.), Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weedon, M.N. (Michael), Wright, A.F. (Alan), Young, L. (L.), Zhai, G. (G.), Zhuang, W.V. (W. V.), Bierut, L.J. (L. J.), Boyd, H.A. (H. A.), Crisponi, L. (Laura), Demerath, E.W. (E. W.), Duijn, C.M. (Cornelia) van, Econs, M.J. (M. J.), Harris, T.B. (Tamara), Bierut, L.J. (Laura), Loos, R.J.F. (Ruth), Ridker, P.M. (Paul), Demerath, E.W. (Ellen), Streeten, E.A. (Elizabeth), Econs, M.J. (Michael), Thorsteinsdottir, U. (Unnur), Widen, E. (E.), Murabito, J. (Joanne), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Crawford, S. (Steve), Crow, S. (Scott), Fichter, M.M. (M. M.), Halmi, K.A. (K. A.), Palotie, A. (Aarno), La Via, M. (Maria), Mitchell, J. (James), Strober, M. (Michael), Rotondo, A. (Alessandro), Woodside, D.B. (D Blake), Keel, P. (Pamela), Lilenfeld, L. (Lisa), Rivadeneira Ramirez, F. (Fernando), Magistretti, P. (Pierre), Montgomery, G.W. (G. W.), Hinney, A. (Anke), Kesselmeier, M. (M.), Jall, S. (S.), Volckmar, A.-L. (A. L.), Föcker, M. (M.), Antel, J. (J.), Heid, I.M. (Iris), Winkler, T.W. (Thomas W.), Grant, S.F.A. (S. F.A.), Guo, Y. (Yongli), Bergen, A.W. (Andrew), Grant, S.F.A. (Struan), Berrettini, W. (Wade), Hakonarson, H. (Hakon), Herpertz-Dahlmann, B. (B.), De Zwaan, M. (M.), Herzog, W. (W.), Ehrlich, S.M. (Stefan), Zipfel, S. (S.), Egberts, K. (Karin), Adan, R. (R.), Brandys, M. (M.), Elburg, A.A. (Annemarie) van, Boraska Perica, V. (V.), Müller, T.D., Tschöp, M.H. (M. H.), Zeggini, E. (Eleftheria), Bulik, C.M. (C. M.), Collier, D.A. (David), Scherag, A. (A.), Hebebrand, J. (J.), Tschop, M. (Matthias), Floyd, J. (Jamie), Thornton, L.M. (Laura), Huckins, L.M. (Laura M), Southam, L. (Lorraine), Rayner, N.W. (Nigel William), Tachmazidou, I. (Ioanna), Klump, K.L. (K. L.), Treasure, J. (Janet), Lewis, C.M. (Cathryn), Schmidt, U. (Ulrike), Tozzi, F. (Federica), Iezebrink, K. (Kirsty), Gorwood, P. (Philip), Kas, M.J.H. (Martien), Favaro, A. (Angela), Santonastaso, P. (Paolo), Fernández-Aranda, F. (Fernando), Gratacos, M. (Monica), Rybakowski, F. (Filip), Dmitrzak-Weglarz, M. (Monika), Kaprio, J. (Jaakko), Keski-Rahkonen, A. (Anna), Raevuori-Helkamaa, A. (Anu), Furth, E.F. (Eric) van, Slof-Op’t Landt, M.C.T. (Margarita C. T.), Hudson, J.I. (James I), Knudsen, G.P.S. (Gun Peggy S.), Monteleone, P. (Palmiero), Kaplan, A.S. (Allan S), Karwautz, A. (Andreas), Li, D. (Dong), Komaki, G. (Gen), Ando, T. (Tetsuya), Inoko, H. (Hidetoshi), Esko, T. (T.), Fischer, K. (Krista), Männik, K. (Katrin), Metspalu, A. (Andres), Baker, J.H. (Jessica H), Cone, R.D. (Roger D), Esko, T. (Tõnu), DeSocio, J.E. (Janiece E), Hilliard, C.E. (Christopher E), O’Toole, J.K. (Julie K), Pantel, J. (Jacques), Szatkiewicz, J.P. (Jin P), Taico, C. (Chrysecolla), Zerwas, S. (Stephanie), Trace, S.E. (Sara E), Davis, O.S.P. (Oliver S.), Helder, S. (Sietske), Bühren, K. (Katharina), Burghardt, R. (Roland), Imgart, H. (Hartmut), Scherag, A. (Andre), Boni, C. (Claudette), Ramoz, N. (Nicolas), Versini, A. (Audrey), Danner, U.N. (Unna N), de Kove, C. (Carolien), Hendriks, J. (Judith), Koeleman, B.P.C. (Bobby P. C.), Ophoff, R.A. (Roel), Strengman, E. (Eric), Bruson, A. (Alice), Clementi, M. (Maurizio), Degortes, D. (Daniela), Forzan, M. (Monica), Tenconi, E. (Elena), Docampo, E. (Elisa), Jiménez-Murcia, G.E.S. (Geòrgia Escaramí Susana), Lissowska, J. (Jolanta), Rajewski, A. (Andrzej), Szeszenia-Dabrowska, N. (Neonila), Slopien, A. (Agnieszka), Hauser, J. (J.), Karhunen, L. (Leila), Meulenbelt, I. (Ingrid), Slagboom, P.E. (Eline), Tortorella, A. (Alfonso), Maj, M. (Mario), Dedoussis, G.V. (George), Dedoussis, G.V. (G. V.), Koeleman, B.P.C. (Bobby), Gonidakis, F. (Fragiskos), Tziouvas, K. (Konstantinos), Tsitsika, A. (Artemis), Papezova, H. (Hana), Slachtova, L. (Lenka), Martaskova, D. (Debora), Kennedy, J.L., Levitan, R.D. (Robert D), Yilmaz, Z. (Zeynep), Huemer, J. (Julia), Koubek, D. (Doris), Merl, E. (Elisabeth), Wagner, G. (Gudrun), Lichtenstein, P. (Paul), Breen, G. (Gerome), Cohen-Woods, S. (Sarah), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Cichon, S. (Sven), Giegling, I. (Ina), Herms, S. (Stefan), Rujescu, D. (Dan), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Sladek, R. (Rob), Gambaro, G. (Giovanni), Soranzo, N. (Nicole), Julia, A. (Antonio), Marsal, S. (Sara), Rabionet, R. (Raquel), Gaborieau, V. (Valerie), Dick, D.M. (Danielle), Palotie, A. (A.), Ripatti, S. (Samuli), Widen, E., Espeseth, T. (Thomas), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Steen, V.M. (Vidar), Le Hellard, S. (Stephanie), Mattingsdal, M. (Morten), Ntalla, I. (Ioanna), Bencko, V. (Vladimir), Foretova, L. (Lenka), Janout, V. (Vladimir), Navratilova, M. (Marie), Pinto, D. (Dalila), Scherer, S.W. (Stephen W), Carlberg, L. (Laura), Schosser, A. (Alexandra), Alfredsson, L. (Lars), Pinto, D. (Duane), Scherer, S.W. (Stephen), Padyukov, L. (Leonid), Finan, C. (Chris), Kalsi, G. (Gursharan), Roberts, M. (Marion), Logan, D.W. (Darren W), Peltonen, L. (Leena Johanna), Ritchie, G.R.S. (Graham R.S.), Barrett, J.C. (Jeffrey), Estivill, X. (Xavier), Sullivan, P.F. (Patrick), Anderson, C.A. (Carl A), McGinnis, R. (Ralph), Sambrook, J. (Jennifer), Stephens, J. (Jonathan), Ouwehand, W.H. (Willem), McArdle, P.F. (P. F.), Ring, S.M. (Susan), Strachan, D.P. (David), Alexander, G. (Graeme), Conlon, P.J. (Peter J), Dominiczak, A. (Anna), Duncanson, A. (Audrey), Padyukov, L. (L.), Langford, C. (Cordelia), Lord, G. (Graham), Conlon, P. (Peter), Sandford, R. (Richard), Sheerin, N. (Neil), Vannberg, F.O. (Frederik O), Blackburn, H. (Hannah), Maxwell, A.P. (A.), Edkins, T. (Ted), Gillman, M.W. (Matthew W.), Gray, E. (Emma), Hunt, S.E. (Sarah E), Nengut, S.-G. (Suna-Gumuscu), Potter, S.C. (Simon), Rich, S.S. (Stephen), Simpkin, D. (Douglas), Whittaker, P. (Pamela), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N. (N.), Benke, K. (K.), Berry, D. (Diane), Boomsma, D.I. (Dorret), Bradfield, J.P. (Jonathan), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cooper, C. (C.), Cousminer, D.L. (Diana), Das, S. (Shikta), Elliott, P. (P.), Evans, D.M. (D. M.), Feenstra, B. (B.), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Freathy, R.M. (Rachel), Gaillard, R. (R.), Geller, F. (Frank), Groen-Blokhuis, M. (Maria), Goh, L.K. (L. K.), Guxens Junyent, M. (Mònica), Hattersley, A.T. (Andrew), Haworth, C.M.A. (Claire M.), Hadley, D. (D.), Heinrich, J. (J.), Hirschhorn, J.N. (Joel), Hocher, B. (Berthold), Holloway, J.W. (J. W.), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (E.), Iñiguez, C. (C.), Jaddoe, V.W. (V. W.), Jarvelin, M.R. (M. R.), Kaakinen, M. (M.), Kilpeläinen, T.O. (Tuomas), Hypponen, E. (Elina), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Cooper, C. (Charles), Lange, L.A. (Leslie), Lawlor, D.A. (D. A.), Lehtimäki, T. (Terho), Lewin, A. (Alex), Elliott, P. (Paul), Lindi, V. (Virpi), Maggi, R. (Reedik), Feenstra, B. (Bjarke), McCarthy, M.I. (M. I.), Melbye, M. (Mads), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (D. O.), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Oken, E. (Emily), Ong, K.K. (K. K.), O'Reilly, P.F. (P. F.), Palmer, C. (Cameron), Panoutsopoulou, K. (K.), Pararajasingham, J. (Jennifer), Pearson, E.R. (E. R.), Pennell, C.E. (Craig), Power, C. (Christopher), Price, T.S. (Thomas), Prokopenko, I. (Inga), Raitakari, O.T. (O. T.), Rodriguez, A. (A.), Salem, R.M. (Rany), Saw, S.M. (S. M.), Sebert, S. (S.), Siitonen, N. (Niina), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Sovio, U. (Ulla), Lawlor, D.A. (Debbie), Sunyer, J. (J.), Taal, H.R. (Rob), Teo, Y.Y. (Y. Y.), Thiering, E. (Elisabeth), Tiesler, C. (C.), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Valcárcel, B. (Beatriz), Teo, Y.Y. (Yik Ying), White, S.J. (Stefan), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (J. F.), Yaghootkar, H. (H.), Elks, C.E. (Cathy), Perry, J.R. (J. R.), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (C.), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (E. M.), Gudbjartsson, D.F. (Daniel), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (P.), Mangino, M. (Massimo), Byrne, E.M. (Enda), Smith, A.V. (Albert), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (J. H.), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Smith, A.V. (Davey), Chanock, S.J. (Stephen), Warrington, M. (M.), Zgaga, L. (L.), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (T.), Ulivi, S. (Shelia), Sunyer, J. (Jordi), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Boerwinkle, E. (E.), Buring, J.E. (Julie), Busonero, F. (F.), Barroso, I.E. (Inês), Chanock, S.J. (S. J.), Warrington, N.M. (Nicole), Couper, D.J. (David), Coviello, A.D. (Andrea), Busonero, F., Faire, U. (Ulf) de, de Geus, E.J. (E. J.), Deloukas, P. (Panagiotis), Döring, A. (Angela), Davey Smith, G. (G.), Adamo, P. (Pio) d', Eiriksdottir, G. (Gudny), Geus, E.J.C. (Eco) de, Hagen, K. (Knut), Ferrucci, L. (L.), Folsom, A.R. (A. R.), Foroud, T. (T.), Garcia, M.E. (M.), Gasparini, P. (P.), Gieger, C. (Christian), Gudnason, V. (V.), Folsom, A.R. (Aaron), Hankinson, S.E. (S. E.), Ferreli, L. (Liana), Gasparini, P. (Paolo), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (F. B.), Illig, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K.T. (K. T.), Kiel, D.P. (Douglas P.), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S. (J. S.), Li, S. (S.), Liu, J. (J.), Levy, D. (D.), Martin, N.G. (N. G.), Aspelund, T. (Thor), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (M.), Ness, A.R. (A. R.), Boerwinkle, E.A. (Eric), Oostra, B.A. (Ben), Peacock, M. (M.), Pare, G. (Guillame), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Cornelis, M. (Marilyn), Polasek, O. (Ozren), Plump, A.S. (A. S.), Peacock, M. (Munro), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Rivadeneira, F. (F.), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (D.), Scuteri, A. (A.), Segrè, A.V. (Ayellet), Foroud, T. (Tatiana), Srinivasan, S.R. (Sathanur), Tammesoo, M.L. (M. L.), Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Scuteri, A. (Angelo), Tryggvadottir, L. (Laufey), Tyrer, J. (J.), Uda, M. (M.), van Dam, R.M. (R. M.), Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weedon, M.N. (Michael), Wright, A.F. (Alan), Young, L. (L.), Zhai, G. (G.), Zhuang, W.V. (W. V.), Bierut, L.J. (L. J.), Boyd, H.A. (H. A.), Crisponi, L. (Laura), Demerath, E.W. (E. W.), Duijn, C.M. (Cornelia) van, Econs, M.J. (M. J.), Harris, T.B. (Tamara), Bierut, L.J. (Laura), Loos, R.J.F. (Ruth), Ridker, P.M. (Paul), Demerath, E.W. (Ellen), Streeten, E.A. (Elizabeth), Econs, M.J. (Michael), Thorsteinsdottir, U. (Unnur), Widen, E. (E.), Murabito, J. (Joanne), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Crawford, S. (Steve), Crow, S. (Scott), Fichter, M.M. (M. M.), Halmi, K.A. (K. A.), Palotie, A. (Aarno), La Via, M. (Maria), Mitchell, J. (James), Strober, M. (Michael), Rotondo, A. (Alessandro), Woodside, D.B. (D Blake), Keel, P. (Pamela), Lilenfeld, L. (Lisa), Rivadeneira Ramirez, F. (Fernando), Magistretti, P. (Pierre), and Montgomery, G.W. (G. W.)
Abstract: The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the associa
Published: 2017
Full Text: View/download PDF

4. Genome-wide association and functional studies identify a role for matrix Gla protein in osteoarthritis of the hand

Author: Hollander, W. (Wouter) den, Boer, C.G. (Cindy G.), Hart, D.J. (Deborah), Yau, M.S. (Michelle S.), Ramos, Y.F.M. (Yolande F.M.), Metrustry, S. (Sarah), Broer, L. (Linda), Deelen, J. (Joris), Cupples, L.A. (Adrienne), Rivadeneira, F. (Fernando), Kloppenburg, M. (Margreet), Peters, M.A.D. (Marjolein), Spector, T.D. (Timothy), Hofman, A. (Albert), Slagboom, P.E. (Eline), Nelissen, R.G.H.H. (Rob), Uitterlinden, A.G. (André), Felson, D., Valdes, A.M. (Ana Maria), Meulenbelt, I. (Ingrid), Van Meurs, J.J.B. (Joyce J. B.), Hollander, W. (Wouter) den, Boer, C.G. (Cindy G.), Hart, D.J. (Deborah), Yau, M.S. (Michelle S.), Ramos, Y.F.M. (Yolande F.M.), Metrustry, S. (Sarah), Broer, L. (Linda), Deelen, J. (Joris), Cupples, L.A. (Adrienne), Rivadeneira, F. (Fernando), Kloppenburg, M. (Margreet), Peters, M.A.D. (Marjolein), Spector, T.D. (Timothy), Hofman, A. (Albert), Slagboom, P.E. (Eline), Nelissen, R.G.H.H. (Rob), Uitterlinden, A.G. (André), Felson, D., Valdes, A.M. (Ana Maria), Meulenbelt, I. (Ingrid), and Van Meurs, J.J.B. (Joyce J. B.)
Abstract: Objective Osteoarthritis (OA) is the most common form of arthritis and the leading cause of disability in the elderly. Of all the joints, genetic predisposition is strongest for OA of the hand; however, only few genetic risk loci for hand OA have been identified. Our aim was to identify novel genes associated with hand OA and examine the underlying mechanism. Methods We performed a genome-wide association study of a quantitative measure of hand OA in 12 784 individuals (discovery: 8743, replication: 4011). Genome-wide significant signals were followed up by analysing gene and allele-specific expression in a RNA sequencing dataset (n=96) of human articular cartilage. Results We found two significantly associated loci in the discovery set: at chr12 (p=3.5 × 10 -10) near the matrix Gla protein (MGP) gene and at chr12 (p=6.1×10 -9) near the CCDC91 gene. The DNA variant near t
Published: 2017
Full Text: View/download PDF

5. Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

Author: Castaño Betancourt, M.C. (Martha), Evans, D.S. (Daniel), Ramos, Y.F.M. (Yolande), Boer, C.G. (Cindy G.), Metrustry, S. (Sarah), Liu, Y. (Youfang), Hollander, W. (Wouter) den, Rooij, J.G.J. (Jeroen) van, Kraus, V.B. (Virginia B.), Yau, M.S. (Michelle S.), Mitchell, B.D. (Braxton), Muir, K. (Kenneth), Hofman, A. (Albert), Doherty, M. (Michael), Doherty, S. (Sally), Zhang, W. (Weiya), Kraaij, R. (Robert), Rivadeneira Ramirez, F. (Fernando), Barrett-Connor, E. (Elizabeth), MacIewicz, R.A. (Rose), Arden, N.K. (Nigel), Nelissen, R.G.H.H. (Rob), Kloppenburg, M. (Margreet), Jordan, J.M. (Joanne M.), Nevitt, M.C. (Michael), Slagboom, P.E. (Eline), Hart, D. (Deborah), Lafeber, F.P.J.G. (Floris), Styrkarsdottir, U. (Unnur), Zeggini, E. (Eleftheria), Evangelou, E. (Evangelos), Spector, T.D. (Timothy), Uitterlinden, A.G. (André), Lane, N.E., Meulenbelt, I. (Ingrid), Valdes, A.M. (Ana Maria), Meurs, J.B.J. (Joyce) van, Castaño Betancourt, M.C. (Martha), Evans, D.S. (Daniel), Ramos, Y.F.M. (Yolande), Boer, C.G. (Cindy G.), Metrustry, S. (Sarah), Liu, Y. (Youfang), Hollander, W. (Wouter) den, Rooij, J.G.J. (Jeroen) van, Kraus, V.B. (Virginia B.), Yau, M.S. (Michelle S.), Mitchell, B.D. (Braxton), Muir, K. (Kenneth), Hofman, A. (Albert), Doherty, M. (Michael), Doherty, S. (Sally), Zhang, W. (Weiya), Kraaij, R. (Robert), Rivadeneira Ramirez, F. (Fernando), Barrett-Connor, E. (Elizabeth), MacIewicz, R.A. (Rose), Arden, N.K. (Nigel), Nelissen, R.G.H.H. (Rob), Kloppenburg, M. (Margreet), Jordan, J.M. (Joanne M.), Nevitt, M.C. (Michael), Slagboom, P.E. (Eline), Hart, D. (Deborah), Lafeber, F.P.J.G. (Floris), Styrkarsdottir, U. (Unnur), Zeggini, E. (Eleftheria), Evangelou, E. (Evangelos), Spector, T.D. (Timothy), Uitterlinden, A.G. (André), Lane, N.E., Meulenbelt, I. (Ingrid), Valdes, A.M. (Ana Maria), and Meurs, J.B.J. (Joyce) van
Abstract: Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547
Published: 2016
Full Text: View/download PDF

6. Translation of clinical problems in osteoarthritis into pathophysiological research goals

Author: Kraan, P.M. (Peter) van der, Berenbaum, F. (Francis), Blanco, F.J. (Francisco J.), Cosimo, D.B. (De Bari), Lafeber, F.P.J.G. (Floris), Hauge, E. (Ellen), Higginbottom, A. (Adele), Ioan-Facsinay, A. (Andrea), Loughlin, J. (John), Meulenbelt, I. (Ingrid), Moilanen, E. (Eeva), Pitsillidou, I. (Irene), Tsezou, A. (Aspasia), Meurs, J.B.J. (Joyce) van, Vincent, T.L., Wittoek, R. (Ruth), Lories, R.J. (Rik), Kraan, P.M. (Peter) van der, Berenbaum, F. (Francis), Blanco, F.J. (Francisco J.), Cosimo, D.B. (De Bari), Lafeber, F.P.J.G. (Floris), Hauge, E. (Ellen), Higginbottom, A. (Adele), Ioan-Facsinay, A. (Andrea), Loughlin, J. (John), Meulenbelt, I. (Ingrid), Moilanen, E. (Eeva), Pitsillidou, I. (Irene), Tsezou, A. (Aspasia), Meurs, J.B.J. (Joyce) van, Vincent, T.L., Wittoek, R. (Ruth), and Lories, R.J. (Rik)
Abstract: Osteoarthritis (OA) accounts for more disability among the elderly than any other disease and is associated with an increased mortality rate. The prevalence in Europe will rise in the future since this continent has a strongly ageing population and an obesity epidemic; obesity and age both being major risk factors for OA. No adequate therapeutic options, besides joint replacement, are available, although they are greatly needed and should be acquired by adequate research investments. However, the perspective on OA from a researcher's point of view is not always aligned with the perspective of a patient with OA. Researchers base their views on OA mainly on abnormalities in structure and function while patients consider OA as a collection of symptoms. In this viewpoint paper, we discuss the possibility of translating the most important clinical problems into pathophysiological research goals to facilitate the translation from bench to bedside and vice versa. This viewpoint is the outcome of a dialogue within the 'European League Against Rheumatism study group on OA' and People with Arthritis/Rheumatism across Europe (PARE) representatives.
Published: 2016
Full Text: View/download PDF

7. Associations between joint effusion in the knee and gene expression levels in the circulation: A meta-analysis

Author: Ramos, Y.F.M. (Yolande), Peters, M.J. (Marjolein), Hollander, W. (Wouter) den, Schiphof, D. (Dieuwke), Hofman, A. (Albert), Uitterlinden, A.G. (André), Oei, E.H.G. (Edwin), Slagboom, P.E. (Eline), Kloppenburg, M. (Margreet), Bloem, J.L. (Johan), Bierma-Zeinstra, S.M. (Sita), Meulenbelt, I. (Ingrid), Meurs, J.B.J. (Joyce) van, Ramos, Y.F.M. (Yolande), Peters, M.J. (Marjolein), Hollander, W. (Wouter) den, Schiphof, D. (Dieuwke), Hofman, A. (Albert), Uitterlinden, A.G. (André), Oei, E.H.G. (Edwin), Slagboom, P.E. (Eline), Kloppenburg, M. (Margreet), Bloem, J.L. (Johan), Bierma-Zeinstra, S.M. (Sita), Meulenbelt, I. (Ingrid), and Meurs, J.B.J. (Joyce) van
Abstract: Objective: To identify molecular biomarkers for early knee osteoarthritis (OA), we examined whether joint effusion in the knee associated with different gene expression levels in the circulation. Materials and Methods: Joint effusion grades measured with magnetic resonance (MR) imaging and gene expression levels in blood were determined in women of the Rotterdam Study (N=135) and GARP (N=98). Associations were examined using linear regression analyses, adjusted for age, fasting status, RNA quality, technical batch effects, blood cell counts, and BMI. To investigate enriched pathways and protein-protein interactions, we used the DAVID and STRING webtools. Results: In a meta-analysis, we identified 257 probes mapping to 189 unique genes in blood that were nominally significantly associated with joint effusion grades in the knee. Several compelling genes were identified such as C1orf38 and NFATC1. Significantly enriched biological pathways were: response to stress, gene expression, negative regulation of intracellular signal transduction, and antigen processing and presentation of exogenous pathways. Conclusion: Meta-analyses and subsequent enriched biological pathways resulted in interesting candidate genes associated with joint effusion that require further characterization. Associations were not transcriptome-wide significant most likely due to limited power. Additional studies are required to replicate our findings in more samples, which will greatly help in understanding the pathophysiology of OA and its relation to inflammation, and may result in biomarkers urgently needed to diagnose OA at an early stage.
Published: 2016
Full Text: View/download PDF

8. The transcriptional landscape of age in human peripheral blood

Author: Peters, M.J. (Marjolein), Joehanes, R. (Roby), Pilling, L.C. (Luke), Schurmann, C. (Claudia), Conneely, K.N. (Karen N.), Powell, J.E. (Joseph), Reinmaa, E. (Eva), Sutphin, G.L. (George L.), Zhernakova, A. (Alexandra), Schramm, K. (Katharina), Wilson, Y.A. (Yana A.), Kobes, S. (Sayuko), Tukiainen, T. (Taru), Ramos, Y.F.M. (Yolande), Göring, H.H.H. (Harald H.), Fornage, M. (Myriam), Liu, Y. (YongMei), Gharib, S.A. (Sina), Stranger, B.E. (Barbara), Jager, P.L. (Philip) de, Aviv, A. (Abraham), Levy, D. (Daniel), Murabito, J. (Joanne), Munson, P.J. (Peter J.), Huan, T. (Tianxiao), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Rooij, J.G.J. (Jeroen) van, Stolk, L. (Lisette), Broer, L. (Linda), Verbiest, M.M.P.J. (Michael), Jhamai, M. (Mila), Arp, P.P. (Pascal), Metspalu, A. (Andres), Tserel, L. (Liina), Milani, L. (Lili), Samani, N.J. (Nilesh), Peterson, P. (Pärt), Kasela, S. (Silva), Codd, V. (Veryan), Peters, A. (Annette), Ward-Caviness, C.K. (Cavin K.), Herder, C. (Christian), Waldenberger, M. (Melanie), Roden, M. (Michael), Singmann, P. (Paula), Zeilinger, S. (Sonja), Illig, T. (Thomas), Homuth, G. (Georg), Grabe, H.J. (Hans Jörgen), Völzke, H. (Henry), Steil, L. (Leif), Kocher, T. (Thomas), Murray, A. (Anna), Melzer, D. (David), Yaghootkar, H. (Hanieh), Bandinelli, S., Moses, E.K. (Eric), Kent, J.W. (Jack), Curran, J.E. (Joanne), Johnson, M.P. (Matthew), Williams-Blangero, S. (Sarah), Westra, H.J. (Harm-Jan), McRae, A.F. (Allan F.), Smith, J.A. (Jennifer A), Kardia, S.L.R. (Sharon), Hovatta, I. (Iiris), Perola, M. (Markus), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Henders, A.K. (Anjali), Martin, N.G. (Nicholas), Smith, A.K. (Alicia K.), Mehta, D. (Divya), Binder, E.B. (Elisabeth B.), Nylocks, K.M. (K. Maria), Kennedy, E.M. (Elizabeth M.), Klengel, T. (Torsten), Ding, J. (Jingzhong), Suchy-Dicey, A. (Astrid), Enquobahrie, D., Brody, J.A. (Jennifer A.), Rotter, J.I. (Jerome I.), Chen, Y.-D.I. (Yii-Der I.), Houwing-Duistermaat, J.J. (Jeanine), Kloppenburg, M. (Margreet), Slagboom, P.E. (Eline), Helmer, Q. (Quinta), Hollander, W. (Wouter) den, Bean, S. (Shannon), Raj, T. (Towfique), Bakhshi, N. (Noman), Wang, Q.P. (Qiao Ping), Oyston, L.J. (Lisa J.), Psaty, B.M. (Bruce), Tracy, R.P. (Russell), Montgomery, G.W. (Grant), Turner, S.T. (Stephen), Blangero, J. (John), Meulenbelt, I. (Ingrid), Ressler, K.J. (Kerry), Yang, J. (Jian), Franke, L. (Lude), Kettunen, J. (Johannes), Visscher, P.M. (Peter), Neely, G.G. (G. Gregory), Korstanje, R. (Ron), Hanson, R.L. (Robert L.), Prokisch, H. (Holger), Ferrucci, L. (Luigi), Esko, T. (Tõnu), Teumer, A. (Alexander), Meurs, J.B.J. (Joyce) van, Johnson, A.D. (Andrew D.), Nalls, M.A. (Michael), Hernandez, D.G. (Dena), Cookson, M.R. (Mark), Gibbs, R.J. (Raphael J.), Hardy, J. (John), Ramasamy, A. (Adaikalavan), Zonderman, A.B. (Alan B.), Dillman, A. (Allissa), Traynor, B. (Bryan), Smith, C. (Colin), Longo, D.L. (Dan L.), Trabzuni, D. (Danyah), Troncoso, J.C. (Juan), Brug, M.P. (Marcel) van der, Weale, M.E. (Michael), O'Brien, R. (Richard), Johnson, R. (Robert), Walker, R. (Robert), Zielke, R.H. (Ronald H.), Arepalli, S. (Sampath), Ryten, M. (Mina), Singleton, A., Peters, M.J. (Marjolein), Joehanes, R. (Roby), Pilling, L.C. (Luke), Schurmann, C. (Claudia), Conneely, K.N. (Karen N.), Powell, J.E. (Joseph), Reinmaa, E. (Eva), Sutphin, G.L. (George L.), Zhernakova, A. (Alexandra), Schramm, K. (Katharina), Wilson, Y.A. (Yana A.), Kobes, S. (Sayuko), Tukiainen, T. (Taru), Ramos, Y.F.M. (Yolande), Göring, H.H.H. (Harald H.), Fornage, M. (Myriam), Liu, Y. (YongMei), Gharib, S.A. (Sina), Stranger, B.E. (Barbara), Jager, P.L. (Philip) de, Aviv, A. (Abraham), Levy, D. (Daniel), Murabito, J. (Joanne), Munson, P.J. (Peter J.), Huan, T. (Tianxiao), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Rooij, J.G.J. (Jeroen) van, Stolk, L. (Lisette), Broer, L. (Linda), Verbiest, M.M.P.J. (Michael), Jhamai, M. (Mila), Arp, P.P. (Pascal), Metspalu, A. (Andres), Tserel, L. (Liina), Milani, L. (Lili), Samani, N.J. (Nilesh), Peterson, P. (Pärt), Kasela, S. (Silva), Codd, V. (Veryan), Peters, A. (Annette), Ward-Caviness, C.K. (Cavin K.), Herder, C. (Christian), Waldenberger, M. (Melanie), Roden, M. (Michael), Singmann, P. (Paula), Zeilinger, S. (Sonja), Illig, T. (Thomas), Homuth, G. (Georg), Grabe, H.J. (Hans Jörgen), Völzke, H. (Henry), Steil, L. (Leif), Kocher, T. (Thomas), Murray, A. (Anna), Melzer, D. (David), Yaghootkar, H. (Hanieh), Bandinelli, S., Moses, E.K. (Eric), Kent, J.W. (Jack), Curran, J.E. (Joanne), Johnson, M.P. (Matthew), Williams-Blangero, S. (Sarah), Westra, H.J. (Harm-Jan), McRae, A.F. (Allan F.), Smith, J.A. (Jennifer A), Kardia, S.L.R. (Sharon), Hovatta, I. (Iiris), Perola, M. (Markus), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Henders, A.K. (Anjali), Martin, N.G. (Nicholas), Smith, A.K. (Alicia K.), Mehta, D. (Divya), Binder, E.B. (Elisabeth B.), Nylocks, K.M. (K. Maria), Kennedy, E.M. (Elizabeth M.), Klengel, T. (Torsten), Ding, J. (Jingzhong), Suchy-Dicey, A. (Astrid), Enquobahrie, D., Brody, J.A. (Jennifer A.), Rotter, J.I. (Jerome I.), Chen, Y.-D.I. (Yii-Der I.), Houwing-Duistermaat, J.J. (Jeanine), Kloppenburg, M. (Margreet), Slagboom, P.E. (Eline), Helmer, Q. (Quinta), Hollander, W. (Wouter) den, Bean, S. (Shannon), Raj, T. (Towfique), Bakhshi, N. (Noman), Wang, Q.P. (Qiao Ping), Oyston, L.J. (Lisa J.), Psaty, B.M. (Bruce), Tracy, R.P. (Russell), Montgomery, G.W. (Grant), Turner, S.T. (Stephen), Blangero, J. (John), Meulenbelt, I. (Ingrid), Ressler, K.J. (Kerry), Yang, J. (Jian), Franke, L. (Lude), Kettunen, J. (Johannes), Visscher, P.M. (Peter), Neely, G.G. (G. Gregory), Korstanje, R. (Ron), Hanson, R.L. (Robert L.), Prokisch, H. (Holger), Ferrucci, L. (Luigi), Esko, T. (Tõnu), Teumer, A. (Alexander), Meurs, J.B.J. (Joyce) van, Johnson, A.D. (Andrew D.), Nalls, M.A. (Michael), Hernandez, D.G. (Dena), Cookson, M.R. (Mark), Gibbs, R.J. (Raphael J.), Hardy, J. (John), Ramasamy, A. (Adaikalavan), Zonderman, A.B. (Alan B.), Dillman, A. (Allissa), Traynor, B. (Bryan), Smith, C. (Colin), Longo, D.L. (Dan L.), Trabzuni, D. (Danyah), Troncoso, J.C. (Juan), Brug, M.P. (Marcel) van der, Weale, M.E. (Michael), O'Brien, R. (Richard), Johnson, R. (Robert), Walker, R. (Robert), Zielke, R.H. (Ronald H.), Arepalli, S. (Sampath), Ryten, M. (Mina), and Singleton, A.
Abstract: Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.
Published: 2015
Full Text: View/download PDF

9. Underlying molecular mechanisms of DIO2 susceptibility in symptomatic osteoarthritis

Author: Bomer, N. (Nils), Hollander, W. (Wouter) den, Ramos, Y.F.M. (Yolande), Bos, S.D. (Steffan), Breggen, R. (Ruud) van der, Lakenberg, N. (Nico), Pepers, B.A. (Barry), Eeden, A.E. (Annelies) van, Darvishan, A. (Arash), Tobi, E.W. (Elmar), Duijnisveld, B.J. (Bouke), Akker, E.B. (Erik) van den, Heijmans, B.T. (Bastiaan), Roon-Mom, W.M.C. (Willeke) van, Verbeek, F.J. (Fons), Osch, G.J.V.M. (Gerjo) van, Nelissen, R.G.H.H. (Rob), Slagboom, P.E. (Eline), Meulenbelt, I. (Ingrid), Bomer, N. (Nils), Hollander, W. (Wouter) den, Ramos, Y.F.M. (Yolande), Bos, S.D. (Steffan), Breggen, R. (Ruud) van der, Lakenberg, N. (Nico), Pepers, B.A. (Barry), Eeden, A.E. (Annelies) van, Darvishan, A. (Arash), Tobi, E.W. (Elmar), Duijnisveld, B.J. (Bouke), Akker, E.B. (Erik) van den, Heijmans, B.T. (Bastiaan), Roon-Mom, W.M.C. (Willeke) van, Verbeek, F.J. (Fons), Osch, G.J.V.M. (Gerjo) van, Nelissen, R.G.H.H. (Rob), Slagboom, P.E. (Eline), and Meulenbelt, I. (Ingrid)
Abstract: Objectives: To investigate how the genetic susceptibility gene DIO2 confers risk to osteoarthritis (OA) onset in humans and to explore whether counteracting the deleterious effect could contribute to novel therapeutic approaches. Methods: Epigenetically regulated expression of DIO2 was explored by assessing methylation of positional CpG-dinucleotides and the respective DIO2 expression in OA-affected and macroscopically preserved articular cartilage from end-stage OA patients. In a human in vitro chondrogenesis model, we measured the effects when thyroid signalling during culturing was either enhanced (excess T3 or lentiviral induced DIO2 overexpression) or decreased (iopanoic acid). Results: OA-related changes in methylation at a specific CpG dinucleotide upstream of DIO2 caused significant upregulation of its expression (ß=4.96; p=0.0016). This effect was enhanced and appeared driven specifically by DIO2 rs225014 risk allele carriers (ß=5.58, p=0.0006). During in vitro chondrogenesis, DIO2 overexpression resulted in a significant reduced capacity of chondrocytes to deposit extracellular matrix (ECM) components, concurrent with significant induction of ECM degrading enzymes (ADAMTS5, MMP13) and markers of mineralisation (ALPL, COL1A1). Given their concurrent and significant upregulation of expression, this process is likely mediated via HIF-2a/RUNX2 signalling. In contrast, we showed that inhibiting deiodinases during in vitro chondrogenesis contributed to prolonged cartilage homeostasis as reflected by significant increased deposition of ECM components and attenuated upregulation of matrix degrading enzymes. Conclusions: Our findings show how genetic variation at DIO2 could confer risk to OA and raised the possibility that counteracting thyroid signalling may be a novel therapeutic approach.
Published: 2014
Full Text: View/download PDF

10. Assessment of osteoarthritis candidate genes in a meta-analysis of nine genome-wide association studies

Author: Rodriguez-Fontenla, C. (Cristina), Calaza, M. (Manuel), Evangelou, E. (Evangelos), Valdes, A.M. (Ana Maria), Arden, N.K. (Nigel), Blanco, F.J., Carr, A.J. (Andrew Jonathan), Chapman, K. (Kay), Deloukas, P. (Panagiotis), Doherty, M. (Michael), Esko, T. (Tõnu), Garcés Aletá, C.M. (Carlos), Gomez-Reino Carnota, J.J. (Juan), Helgadottir, H.T. (Hafdis), Hofman, A. (Albert), Jonsdottir, I. (Ingileif), Kerkhof, J.M. (Hanneke), Kloppenburg, M. (Margreet), McCaskie, A. (Andrew), Ntzani, E.E. (Evangelia), Ollier, W.E.R. (William), Oreiro, N. (Natividad), Panoutsopoulou, K. (Kalliope), Ralston, S.H. (Stuart), Ramos, Y.F.M. (Yolande), Riancho, J.A. (José), Rivadeneira Ramirez, F. (Fernando), Slagboom, P.E. (Eline), Styrkarsdottir, U. (Unnur), Thorsteinsdottir, U. (Unnur), Thorleifsson, G. (Gudmar), Tsezou, A. (Aspasia), Uitterlinden, A.G. (André), Wallis, G.A. (Gillian), Wilkinson, J.M. (Mark), Zhai, G. (Guangju), Zhu, Y. (Yanyan), Felson, D., Ioannidis, J.P.A. (John), Loughlin, J. (John), Metspalu, A. (Andres), Meulenbelt, I. (Ingrid), Zwart, J-A. (John-Anker), Meurs, J.B.J. (Joyce) van, Zeggini, E. (Eleftheria), Spector, T.D. (Timothy), Gonzalez, A. (Antonio), Rodriguez-Fontenla, C. (Cristina), Calaza, M. (Manuel), Evangelou, E. (Evangelos), Valdes, A.M. (Ana Maria), Arden, N.K. (Nigel), Blanco, F.J., Carr, A.J. (Andrew Jonathan), Chapman, K. (Kay), Deloukas, P. (Panagiotis), Doherty, M. (Michael), Esko, T. (Tõnu), Garcés Aletá, C.M. (Carlos), Gomez-Reino Carnota, J.J. (Juan), Helgadottir, H.T. (Hafdis), Hofman, A. (Albert), Jonsdottir, I. (Ingileif), Kerkhof, J.M. (Hanneke), Kloppenburg, M. (Margreet), McCaskie, A. (Andrew), Ntzani, E.E. (Evangelia), Ollier, W.E.R. (William), Oreiro, N. (Natividad), Panoutsopoulou, K. (Kalliope), Ralston, S.H. (Stuart), Ramos, Y.F.M. (Yolande), Riancho, J.A. (José), Rivadeneira Ramirez, F. (Fernando), Slagboom, P.E. (Eline), Styrkarsdottir, U. (Unnur), Thorsteinsdottir, U. (Unnur), Thorleifsson, G. (Gudmar), Tsezou, A. (Aspasia), Uitterlinden, A.G. (André), Wallis, G.A. (Gillian), Wilkinson, J.M. (Mark), Zhai, G. (Guangju), Zhu, Y. (Yanyan), Felson, D., Ioannidis, J.P.A. (John), Loughlin, J. (John), Metspalu, A. (Andres), Meulenbelt, I. (Ingrid), Zwart, J-A. (John-Anker), Meurs, J.B.J. (Joyce) van, Zeggini, E. (Eleftheria), Spector, T.D. (Timothy), and Gonzalez, A. (Antonio)
Abstract: Objective To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA. Methods A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiology (HuGE) Navigator. All of their single-nucleotide polymorphisms (SNPs) with an allele frequency of >5% were assessed by fixed-effects meta-analysis of 9 genome-wide association studies (GWAS) that included 5,636 patients with knee OA and 16,972 control subjects and 4,349 patients with hip OA and 17,836 control subjects of European ancestry. An additional 5,921 individuals were genotyped for significantly associated SNPs in the meta-analysis. After correction for the number of independent tests, P values less than 1.58 × 10-5 were considered significant. Results SNPs at only 2 of the 199 candidate genes (COL11A1 and VEGF) were associated with OA in the meta-analysis. Two SNPs in COL11A1 showed association with hip OA in the combined analysis: rs4907986 (P = 1.29 × 10-5, odds ratio [OR] 1.12, 95% confidence interval [95% CI] 1.06-1.17) and rs1241164 (P = 1.47 × 10-5, OR 0.82, 95% CI 0.74-0.89). The sex-stratified analysis also showed association of COL11A1 SNP rs4908291 in women (P = 1.29 × 10-5, OR 0.87, 95% CI 0.82-0.92); this SNP showed linkage disequilibrium with rs4907986. A single SNP of VEGF, rs833058, showed association with hip OA in men (P = 1.35 × 10-5, OR 0.85, 95% CI 0.79-0.91). After additional samples were genotyped, association at one of the COL11A1 signals was reinforced, whereas association at VEGF was slightly weakened. Conclusion Two candidate genes, COL11A1 and VEGF, were significantly associated with OA in this focused meta-analysis. The remaining candidate genes were not associated. Copyright
Published: 2014
Full Text: View/download PDF

11. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

Author: Evangelou, E. (Evangelos), Kerkhof, J.M. (Hanneke), Styrkarsdottir, U. (Unnur), Ntzani, E.E. (Evangelia), Bos, S.D. (Steffan), Esko, T. (Tõnu), Evans, D.S. (Daniel), Metrustry, S. (Sarah), Panoutsopoulou, K. (Kalliope), Ramos, Y.F.M. (Yolande), Thorleifsson, G. (Gudmar), Tsilidis, K.K. (Konstantinos), Arden, N.K. (Nigel), Aslam, N. (Nadim), Bellamy, N. (Nicholas), Birrell, F. (Fraser), Blanco, F.J., Carr, A.J. (Andrew Jonathan), Chapman, K. (Kay), Day-Williams, A.G. (Aaron), Deloukas, P. (Panagiotis), Doherty, M. (Michael), Engström, G., Helgadottir, H.T. (Hafdis), Hofman, A. (Albert), Ingvarsson, T. (Torvaldur), Jonsson, H. (Helgi), Keis, A. (Aime), Keurentjes, J.C. (J. Christiaan), Kloppenburg, M. (Margreet), Lind, P.A. (Penelope), McCaskie, A. (Andrew), Martin, N.G. (Nicholas), Milani, A.L. (Alfredo), Montgomery, G.W., Nelissen, R.G.H.H. (Rob), Nevitt, M.C. (Michael), Nilsson, P. (Peter), Ollier, W.E.R. (William), Parimi, N. (Neeta), Rai, A. (Ashok), Ralston, S.H., Reed, M.R. (Mike), Riancho, J.A. (José), Rivadeneira Ramirez, F. (Fernando), Rodriguez-Fontenla, C. (Cristina), Southam, L. (Lorraine), Thorsteinsdottir, U. (Unnur), Tsezou, A. (Aspasia), Wallis, G.A. (Gillian), Wilkinson, J.M. (Mark), Gonzalez, A. (Antonio), Lane, N.E., Lohmander, L.S. (Stefan), Loughlin, J. (John), Metspalu, A. (Andres), Uitterlinden, A.G. (André), Jonsdottir, I. (Ingileif), Zwart, J-A. (John-Anker), Slagboom, P.E. (Eline), Zeggini, E. (Eleftheria), Meulenbelt, I. (Ingrid), Ioannidis, J.P.A. (John), Spector, T.D. (Timothy), Meurs, J.B.J. (Joyce) van, Valdes, A.M. (Ana Maria), Evangelou, E. (Evangelos), Kerkhof, J.M. (Hanneke), Styrkarsdottir, U. (Unnur), Ntzani, E.E. (Evangelia), Bos, S.D. (Steffan), Esko, T. (Tõnu), Evans, D.S. (Daniel), Metrustry, S. (Sarah), Panoutsopoulou, K. (Kalliope), Ramos, Y.F.M. (Yolande), Thorleifsson, G. (Gudmar), Tsilidis, K.K. (Konstantinos), Arden, N.K. (Nigel), Aslam, N. (Nadim), Bellamy, N. (Nicholas), Birrell, F. (Fraser), Blanco, F.J., Carr, A.J. (Andrew Jonathan), Chapman, K. (Kay), Day-Williams, A.G. (Aaron), Deloukas, P. (Panagiotis), Doherty, M. (Michael), Engström, G., Helgadottir, H.T. (Hafdis), Hofman, A. (Albert), Ingvarsson, T. (Torvaldur), Jonsson, H. (Helgi), Keis, A. (Aime), Keurentjes, J.C. (J. Christiaan), Kloppenburg, M. (Margreet), Lind, P.A. (Penelope), McCaskie, A. (Andrew), Martin, N.G. (Nicholas), Milani, A.L. (Alfredo), Montgomery, G.W., Nelissen, R.G.H.H. (Rob), Nevitt, M.C. (Michael), Nilsson, P. (Peter), Ollier, W.E.R. (William), Parimi, N. (Neeta), Rai, A. (Ashok), Ralston, S.H., Reed, M.R. (Mike), Riancho, J.A. (José), Rivadeneira Ramirez, F. (Fernando), Rodriguez-Fontenla, C. (Cristina), Southam, L. (Lorraine), Thorsteinsdottir, U. (Unnur), Tsezou, A. (Aspasia), Wallis, G.A. (Gillian), Wilkinson, J.M. (Mark), Gonzalez, A. (Antonio), Lane, N.E., Lohmander, L.S. (Stefan), Loughlin, J. (John), Metspalu, A. (Andres), Uitterlinden, A.G. (André), Jonsdottir, I. (Ingileif), Zwart, J-A. (John-Anker), Slagboom, P.E. (Eline), Zeggini, E. (Eleftheria), Meulenbelt, I. (Ingrid), Ioannidis, J.P.A. (John), Spector, T.D. (Timothy), Meurs, J.B.J. (Joyce) van, and Valdes, A.M. (Ana Maria)
Abstract: Objectives: Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods: We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. Results: We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10-9and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10-8) and follow-up studies (p=7.3×10-4). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10-7, OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10-6, OR=1.27 in male specific analysis). Conclusions: Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
Published: 2014
Full Text: View/download PDF

12. The DOT1L rs12982744 polymorphism is associated with osteoarthritis of the hip with genome-wide statistical significance in males

Author: Evangelou, E. (Evangelos), Valdes, A.M. (Ana Maria), Castaño Betancourt, M.C. (Martha), Doherty, M. (Michael), Doherty, S. (Sally), Esko, T. (Tõnu), Ingvarsson, T. (Torvaldur), Ioannidis, J.P.A. (John), Kloppenburg, M. (Margreet), Metspalu, A. (Andres), Ntzani, E.E. (Evangelia), Panoutsopoulou, K. (Kalliope), Slagboom, P.E. (Eline), Southam, L. (Lorraine), Spector, T.D. (Timothy), Styrkarsdottir, U. (Unnur), StefanSon, K. (Kari), Uitterlinden, A.G. (André), Wheeler, M. (Margaret), Zeggini, E. (Eleftheria), Meulenbelt, I. (Ingrid), Meurs, J.B.J. (Joyce) van, Evangelou, E. (Evangelos), Valdes, A.M. (Ana Maria), Castaño Betancourt, M.C. (Martha), Doherty, M. (Michael), Doherty, S. (Sally), Esko, T. (Tõnu), Ingvarsson, T. (Torvaldur), Ioannidis, J.P.A. (John), Kloppenburg, M. (Margreet), Metspalu, A. (Andres), Ntzani, E.E. (Evangelia), Panoutsopoulou, K. (Kalliope), Slagboom, P.E. (Eline), Southam, L. (Lorraine), Spector, T.D. (Timothy), Styrkarsdottir, U. (Unnur), StefanSon, K. (Kari), Uitterlinden, A.G. (André), Wheeler, M. (Margaret), Zeggini, E. (Eleftheria), Meulenbelt, I. (Ingrid), and Meurs, J.B.J. (Joyce) van
Published: 2013
Full Text: View/download PDF

13. Genome-wide association study meta-analysis of chronic widespread pain: Evidence for involvement of the 5p15.2 region

Author: Peters, M.J. (Marjolein), Broer, L. (Linda), Willemen, H.L.D.M. (Hanneke), Eiriksdottir, G. (Gudny), Hocking, L.J. (Lynne), Holliday, K.L. (Kate), Horan, M. (Mike), Meulenbelt, I. (Ingrid), Neogi, T. (Tuhina), Popham, M. (Maria), Schmidt, C.O. (Carsten Oliver), Soni, B., Valdes, A.M. (Ana Maria), Amin, N. (Najaf), Dennison, E.M. (Elaine), Eijkelkamp, B. (Bart), Harris, T.B. (Tamara), Hart, D.J. (Deborah), Hofman, A. (Albert), Huygen, F.J.P.M. (Frank), Jameson, K. (Karen), Jones, G.T. (Gregory), Launer, L.J. (Lenore), Kerkhof, J.M. (Hanneke), Kruijf, M. (Marjolein) de, McBeth, J. (John), Kloppenburg, M. (Margreet), Ollier, W.E.R. (William), Oostra, B.A. (Ben), Payton, A. (Antony), Rivadeneira Ramirez, F. (Fernando), Smith, B.H. (Blair), Smith, A.V. (Davey), Stolk, L. (Lisette), Teumer, A. (Alexander), Thomson, W. (Wendy), Uitterlinden, A.G. (André), Wang, K. (Ke), Wingerden, S. (Sophie) van, Arden, N.K. (Nigel), Cooper, C. (Charles), Felson, D., Gudnason, V. (Vilmundur), Macfarlane, G.J. (Gary), Pendleton, N. (Neil), Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Volzke, H. (Henry), Kavelaars, A. (Annemieke), Duijn, C.M. (Cornelia) van, Williams, F.M. (Frances), Meurs, J.B.J. (Joyce) van, Peters, M.J. (Marjolein), Broer, L. (Linda), Willemen, H.L.D.M. (Hanneke), Eiriksdottir, G. (Gudny), Hocking, L.J. (Lynne), Holliday, K.L. (Kate), Horan, M. (Mike), Meulenbelt, I. (Ingrid), Neogi, T. (Tuhina), Popham, M. (Maria), Schmidt, C.O. (Carsten Oliver), Soni, B., Valdes, A.M. (Ana Maria), Amin, N. (Najaf), Dennison, E.M. (Elaine), Eijkelkamp, B. (Bart), Harris, T.B. (Tamara), Hart, D.J. (Deborah), Hofman, A. (Albert), Huygen, F.J.P.M. (Frank), Jameson, K. (Karen), Jones, G.T. (Gregory), Launer, L.J. (Lenore), Kerkhof, J.M. (Hanneke), Kruijf, M. (Marjolein) de, McBeth, J. (John), Kloppenburg, M. (Margreet), Ollier, W.E.R. (William), Oostra, B.A. (Ben), Payton, A. (Antony), Rivadeneira Ramirez, F. (Fernando), Smith, B.H. (Blair), Smith, A.V. (Davey), Stolk, L. (Lisette), Teumer, A. (Alexander), Thomson, W. (Wendy), Uitterlinden, A.G. (André), Wang, K. (Ke), Wingerden, S. (Sophie) van, Arden, N.K. (Nigel), Cooper, C. (Charles), Felson, D., Gudnason, V. (Vilmundur), Macfarlane, G.J. (Gary), Pendleton, N. (Neil), Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Volzke, H. (Henry), Kavelaars, A. (Annemieke), Duijn, C.M. (Cornelia) van, Williams, F.M. (Frances), and Meurs, J.B.J. (Joyce) van
Published: 2013
Full Text: View/download PDF

14. A Meta-Analysis of Thyroid-Related Traits Reveals Novel Loci and Gender-Specific Differences in the Regulation of Thyroid Function

Author: Porcu, E. (Eleonora), Medici, M. (Marco), Pistis, G. (Giorgio), Volpato, C.B., Wilson, S.G. (Scott), Cappola, A.R. (Anne), Bos, S.D. (Steffan), Deelen, J. (Joris), Heijer, M. (Martin) den, Freathy, R.M. (Rachel), Lahti, J. (Jari), Liu, C. (Chunyu), Lopez, L.M. (Lorna), Nolte, I.M. (Ilja), O´Connell, J.R., Tanaka, T. (Toshiko), Trompet, S. (Stella), Arnold, A.M. (Alice), Bandinelli, S. (Stefania), Beekman, M. (Marian), Böhringer, S. (Stefan), Brown, S.J. (Stephen), Buckley, B.M. (Brendan M.), Camaschella, C. (Clara), Craen, A.J. (Anton) de, Davies, G. (Gail), Visser, M.C.H. (Marieke) de, Ford, I. (Ian), Forsen, T. (Tom), Frayling, T.M. (Timothy), Fugazzola, L. (Laura), Gögele, M. (Martin), Hattersley, A.T. (Andrew), Hermus, A.R.M.M. (Ad), Hofman, A. (Albert), Houwing-Duistermaat, J.J. (Jeanine), Jensen, R.A. (Richard), Kajantie, E. (Eero), Kloppenburg, M. (Margreet), Lim, E.M. (Ee Mun), Masciullo, C. (Corrado), Mariotti, S. (Stefano), Minelli, C. (Cosetta), Mitchell, B.D. (Braxton), Nagaraja, R. (Ramaiah), Netea-Maier, R.T. (Romana), Palotie, A. (Aarno), Persani, L. (Luca), Piras, M.G. (Maria Grazia), Psaty, B.M. (Bruce), Räikkönen, K. (Katri), Richards, J.B. (Brent), Rivadeneira Ramirez, F. (Fernando), Sala, C. (Cinzia), Sabra, M.M. (Mona), Sattar, N. (Naveed), Shields, B.M. (Beverley), Soranzo, N. (Nicole), Starr, J.M. (John), Stott, D.J. (David. J.), Sweep, F.C. (Fred), Usala, G., Klauw, M.M. (Melanie) van der, Heemst, D. (Diana) van, Mol-van Mullem, A.A.A. (Alies) van, Vermeulen, S.H. (Sita), Walsh, J.P. (John), Westendorp, R.G.J. (Rudi), Widen, E. (Elisabeth), Zhai, G. (Guangju), Cucca, F. (Francesco), Deary, I.J. (Ian), Visser, W.E. (Edward), Eriksson, J.G. (Johan), Ferrucci, L. (Luigi), Fox, C. (Craig), Jukema, J.W. (Jan Wouter), Kiemeney, L.A.L.M. (Bart), Pramstaller, P.P. (Peter Paul), Schlessinger, D., Shuldiner, A.R. (Alan), Slagboom, P.E. (Eline), Uitterlinden, A.G. (André), Vaidya, B. (Bijay), Visser, T.J. (Theo), Wolffenbuttel, B.H.R. (Bruce), Meulenbelt, I. (Ingrid), Rotter, J.I. (Jerome), Spector, T.D. (Timothy), Hicks, A.A. (Andrew), Toniolo, D. (Daniela), Sanna, S. (Serena), Peeters, R.P. (Robin), Naitza, S. (Silvia), Porcu, E. (Eleonora), Medici, M. (Marco), Pistis, G. (Giorgio), Volpato, C.B., Wilson, S.G. (Scott), Cappola, A.R. (Anne), Bos, S.D. (Steffan), Deelen, J. (Joris), Heijer, M. (Martin) den, Freathy, R.M. (Rachel), Lahti, J. (Jari), Liu, C. (Chunyu), Lopez, L.M. (Lorna), Nolte, I.M. (Ilja), O´Connell, J.R., Tanaka, T. (Toshiko), Trompet, S. (Stella), Arnold, A.M. (Alice), Bandinelli, S. (Stefania), Beekman, M. (Marian), Böhringer, S. (Stefan), Brown, S.J. (Stephen), Buckley, B.M. (Brendan M.), Camaschella, C. (Clara), Craen, A.J. (Anton) de, Davies, G. (Gail), Visser, M.C.H. (Marieke) de, Ford, I. (Ian), Forsen, T. (Tom), Frayling, T.M. (Timothy), Fugazzola, L. (Laura), Gögele, M. (Martin), Hattersley, A.T. (Andrew), Hermus, A.R.M.M. (Ad), Hofman, A. (Albert), Houwing-Duistermaat, J.J. (Jeanine), Jensen, R.A. (Richard), Kajantie, E. (Eero), Kloppenburg, M. (Margreet), Lim, E.M. (Ee Mun), Masciullo, C. (Corrado), Mariotti, S. (Stefano), Minelli, C. (Cosetta), Mitchell, B.D. (Braxton), Nagaraja, R. (Ramaiah), Netea-Maier, R.T. (Romana), Palotie, A. (Aarno), Persani, L. (Luca), Piras, M.G. (Maria Grazia), Psaty, B.M. (Bruce), Räikkönen, K. (Katri), Richards, J.B. (Brent), Rivadeneira Ramirez, F. (Fernando), Sala, C. (Cinzia), Sabra, M.M. (Mona), Sattar, N. (Naveed), Shields, B.M. (Beverley), Soranzo, N. (Nicole), Starr, J.M. (John), Stott, D.J. (David. J.), Sweep, F.C. (Fred), Usala, G., Klauw, M.M. (Melanie) van der, Heemst, D. (Diana) van, Mol-van Mullem, A.A.A. (Alies) van, Vermeulen, S.H. (Sita), Walsh, J.P. (John), Westendorp, R.G.J. (Rudi), Widen, E. (Elisabeth), Zhai, G. (Guangju), Cucca, F. (Francesco), Deary, I.J. (Ian), Visser, W.E. (Edward), Eriksson, J.G. (Johan), Ferrucci, L. (Luigi), Fox, C. (Craig), Jukema, J.W. (Jan Wouter), Kiemeney, L.A.L.M. (Bart), Pramstaller, P.P. (Peter Paul), Schlessinger, D., Shuldiner, A.R. (Alan), Slagboom, P.E. (Eline), Uitterlinden, A.G. (André), Vaidya, B. (Bijay), Visser, T.J. (Theo), Wolffenbuttel, B.H.R. (Bruce), Meulenbelt, I. (Ingrid), Rotter, J.I. (Jerome), Spector, T.D. (Timothy), Hicks, A.A. (Andrew), Toniolo, D. (Daniela), Sanna, S. (Serena), Peeters, R.P. (Robin), and Naitza, S. (Silvia)
Published: 2013
Full Text: View/download PDF

15. 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: Dastani, Z. (Zari), Hivert, M.-F. (Marie-France), Timpson, N.J. (Nicholas), Perry, J.R.B. (John), Yuan, X. (Xin), Scott, R.A. (Robert), Hennemann, P. (Peter), Heid, I.M. (Iris), Kizer, J.R. (Jorge), Lyytikäinen, L.-P. (Leo-Pekka), Fuchsberger, C. (Christian), Tanaka, T. (Toshiko), Morris, A.P. (Andrew), Small, K.S. (Kerrin), Isaacs, A.J. (Aaron), Beekman, M. (Marian), Coassin, S. (Stefan), Lohman, K. (Kurt), Qi, L. (Lu), Kanoni, S. (Stavroula), Pankow, J.S. (James), Uh, H.-W. (Hae-Won), Wu, Y. (Ying), Bidulescu, A. (Aurelian), Rasmussen-Torvik, L.J. (Laura), Greenwood, C.M.T. (Celia), Ladouceur, M. (Martin), Grimsby, J.L. (Jonna), Manning, A.K. (Alisa), Liu, C.-T. (Ching-Ti), Kooner, J.S. (Jaspal), Mooser, V. (Vincent), Vollenweider, P. (Peter), Kapur, K. (Karen), Chambers, J. (John), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Frants, R.R. (Rune), Willems van Dijk, J.A.P. (Ko), Oostra, B.A. (Ben), Willems, S.M. (Sara), Lamina, C. (Claudia), Winkler, T.W. (Thomas), Psaty, B.M. (Bruce), Tracy, R.P. (Russell), Brody, J.A. (Jennifer A.), Chen, I. (Ida), Viikari, J. (Jorma), Kähönen, M. (Mika), Pramstaller, P.P. (Peter Paul), Evans, D.M. (David), St Pourcain, B. (Beate), Sattar, N. (Naveed), Wood, A.R. (Andrew), Bandinelli, S. (Stefania), Carlson, O.D. (Olga), Egan, J.M. (Josephine), Böhringer, S. (Stefan), Heemst, D. (Diana) van, Kedenko, L. (Lyudmyla), Kristiansson, K. (Kati), Nuotio, M.-L. (Marja-Liisa), Loo, B.-M. (Britt-Marie), Harris, T.B. (Tamara), Garcia, M. (Melissa), Kanaya, A. (Alka), Haun, M. (Margot), Klopp, N. (Norman), Wichmann, H.E. (Erich), Deloukas, P. (Panagiotis), Katsareli, E. (Efi), Couper, D.J. (David), Duncan, B.B. (Bruce), Kloppenburg, M. (Margreet), Adair, L.S. (Linda), Borja, J.B. (Judith), Wilson, J.G. (James), Musani, S. (Solomon), Guo, X. (Xiuqing), Johnson, T. (Toby), Semple, R.K. (Robert), Teslovich, T.M. (Tanya), Allison, M.A. (Matthew), Redline, S. (Susan), Buxbaum, S.G. (Sarah), Mohlke, K.L. (Karen), Meulenbelt, I. (Ingrid), Ballantyne, C. (Christie), Dedoussis, G.V. (George), Hu, F.B. (Frank), Liu, Y. (YongMei), Paulweber, B. (Bernhard), Spector, T.D. (Timothy), Slagboom, P.E. (Eline), Ferrucci, L. (Luigi), Jula, A. (Antti), Perola, M. (Markus), Raitakari, O.T. (Olli T.), Florez, J.C. (Jose), Salomaa, V. (Veikko), Eriksson, J.G. (Johan), Frayling, T.M. (Timothy), Hicks, A.A. (Andrew), Lehtimäki, T. (Terho), Smith, G.D. (George Davey), Siscovick, D.S. (David), Kronenberg, F. (Florian), Duijn, C.M. (Cornelia) van, Loos, R.J.F. (Ruth), Waterworth, D.M. (Dawn), Meigs, J.B. (James), Dupuis, J. (Josée), Richards, J.B. (Brent), Dastani, Z. (Zari), Hivert, M.-F. (Marie-France), Timpson, N.J. (Nicholas), Perry, J.R.B. (John), Yuan, X. (Xin), Scott, R.A. (Robert), Hennemann, P. (Peter), Heid, I.M. (Iris), Kizer, J.R. (Jorge), Lyytikäinen, L.-P. (Leo-Pekka), Fuchsberger, C. (Christian), Tanaka, T. (Toshiko), Morris, A.P. (Andrew), Small, K.S. (Kerrin), Isaacs, A.J. (Aaron), Beekman, M. (Marian), Coassin, S. (Stefan), Lohman, K. (Kurt), Qi, L. (Lu), Kanoni, S. (Stavroula), Pankow, J.S. (James), Uh, H.-W. (Hae-Won), Wu, Y. (Ying), Bidulescu, A. (Aurelian), Rasmussen-Torvik, L.J. (Laura), Greenwood, C.M.T. (Celia), Ladouceur, M. (Martin), Grimsby, J.L. (Jonna), Manning, A.K. (Alisa), Liu, C.-T. (Ching-Ti), Kooner, J.S. (Jaspal), Mooser, V. (Vincent), Vollenweider, P. (Peter), Kapur, K. (Karen), Chambers, J. (John), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Frants, R.R. (Rune), Willems van Dijk, J.A.P. (Ko), Oostra, B.A. (Ben), Willems, S.M. (Sara), Lamina, C. (Claudia), Winkler, T.W. (Thomas), Psaty, B.M. (Bruce), Tracy, R.P. (Russell), Brody, J.A. (Jennifer A.), Chen, I. (Ida), Viikari, J. (Jorma), Kähönen, M. (Mika), Pramstaller, P.P. (Peter Paul), Evans, D.M. (David), St Pourcain, B. (Beate), Sattar, N. (Naveed), Wood, A.R. (Andrew), Bandinelli, S. (Stefania), Carlson, O.D. (Olga), Egan, J.M. (Josephine), Böhringer, S. (Stefan), Heemst, D. (Diana) van, Kedenko, L. (Lyudmyla), Kristiansson, K. (Kati), Nuotio, M.-L. (Marja-Liisa), Loo, B.-M. (Britt-Marie), Harris, T.B. (Tamara), Garcia, M. (Melissa), Kanaya, A. (Alka), Haun, M. (Margot), Klopp, N. (Norman), Wichmann, H.E. (Erich), Deloukas, P. (Panagiotis), Katsareli, E. (Efi), Couper, D.J. (David), Duncan, B.B. (Bruce), Kloppenburg, M. (Margreet), Adair, L.S. (Linda), Borja, J.B. (Judith), Wilson, J.G. (James), Musani, S. (Solomon), Guo, X. (Xiuqing), Johnson, T. (Toby), Semple, R.K. (Robert), Teslovich, T.M. (Tanya), Allison, M.A. (Matthew), Redline, S. (Susan), Buxbaum, S.G. (Sarah), Mohlke, K.L. (Karen), Meulenbelt, I. (Ingrid), Ballantyne, C. (Christie), Dedoussis, G.V. (George), Hu, F.B. (Frank), Liu, Y. (YongMei), Paulweber, B. (Bernhard), Spector, T.D. (Timothy), Slagboom, P.E. (Eline), Ferrucci, L. (Luigi), Jula, A. (Antti), Perola, M. (Markus), Raitakari, O.T. (Olli T.), Florez, J.C. (Jose), Salomaa, V. (Veikko), Eriksson, J.G. (Johan), Frayling, T.M. (Timothy), Hicks, A.A. (Andrew), Lehtimäki, T. (Terho), Smith, G.D. (George Davey), Siscovick, D.S. (David), Kronenberg, F. (Florian), Duijn, C.M. (Cornelia) van, Loos, R.J.F. (Ruth), Waterworth, D.M. (Dawn), Meigs, J.B. (James), Dupuis, J. (Josée), and Richards, J.B. (Brent)
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- choles
Published: 2012
Full Text: View/download PDF

16. Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: The TREAT-OA consortium

Author: Kerkhof, J.M. (Hanneke), Meulenbelt, I. (Ingrid), Akune, T. (Toru), Arden, N.K. (Nigel), Aromaa, A. (Arpo), Bierma-Zeinstra, S.M. (Sita), Cooper, C. (Charles), Dai, J., Doherty, M. (Michael), Doherty, S. (Sally), Felson, D., Gonzalez, A. (Antonio), Gordon, A., Harilainen, A. (Arsi), Hart, D.J., Hauksson, V.B. (Valdimar), Heliovaara, M. (Markku), Hofman, A. (Albert), Ikegawa, S., Ingvarsson, T. (Torvaldur), Jiang, Q., Jonsson, H., Jonsdottir, I. (Ingileif), Kawaguchi, H., Kloppenburg, M. (Margreet), Kujala, U.M. (Urho), Lane, N.E., Leino-Arjas, P. (Päivi I.), Lohmander, L.S. (Stefan), Luyten, F.P. (Frank), Malizos, K.N. (Konstantinos), Nakajima, M., Nevitt, M.C. (Michael), Pols, H.A.P. (Huib), Rivadeneira Ramirez, F. (Fernando), Shi, D., Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Stefansson, K. (Kari), Sudo, A. (Akihiro), Tamm, A., Tamm, A.E. (Aile), Tsezou, A. (Aspasia), Uchida, A., Uitterlinden, A.G. (André), Wilkinson, J.M. (Mark), Yoshimura, N., Valdes, A.M. (Ana Maria), Meurs, J.B.J. (Joyce) van, Carr, A.J. (Andrew Jonathan), Kerkhof, J.M. (Hanneke), Meulenbelt, I. (Ingrid), Akune, T. (Toru), Arden, N.K. (Nigel), Aromaa, A. (Arpo), Bierma-Zeinstra, S.M. (Sita), Cooper, C. (Charles), Dai, J., Doherty, M. (Michael), Doherty, S. (Sally), Felson, D., Gonzalez, A. (Antonio), Gordon, A., Harilainen, A. (Arsi), Hart, D.J., Hauksson, V.B. (Valdimar), Heliovaara, M. (Markku), Hofman, A. (Albert), Ikegawa, S., Ingvarsson, T. (Torvaldur), Jiang, Q., Jonsson, H., Jonsdottir, I. (Ingileif), Kawaguchi, H., Kloppenburg, M. (Margreet), Kujala, U.M. (Urho), Lane, N.E., Leino-Arjas, P. (Päivi I.), Lohmander, L.S. (Stefan), Luyten, F.P. (Frank), Malizos, K.N. (Konstantinos), Nakajima, M., Nevitt, M.C. (Michael), Pols, H.A.P. (Huib), Rivadeneira Ramirez, F. (Fernando), Shi, D., Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Stefansson, K. (Kari), Sudo, A. (Akihiro), Tamm, A., Tamm, A.E. (Aile), Tsezou, A. (Aspasia), Uchida, A., Uitterlinden, A.G. (André), Wilkinson, J.M. (Mark), Yoshimura, N., Valdes, A.M. (Ana Maria), Meurs, J.B.J. (Joyce) van, and Carr, A.J. (Andrew Jonathan)
Abstract: Objective: To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Methods: Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I
Published: 2011
Full Text: View/download PDF

17. A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22

Author: Kerkhof, J.M. (Hanneke), Lories, R.J. (Rik), Meulenbelt, I. (Ingrid), Jonsdottir, I. (Ingileif), Valdes, A.M. (Ana Maria), Arp, P.P. (Pascal), Ingvarsson, T. (Torvaldur), Jhamai, M. (Mila), Jonsson, H. (Helgi), Stolk, L. (Lisette), Thorleifsson, G. (Gudmar), Zhai, G. (Guangju), Zhang, F. (Feng), Zhu, Y. (Yicheng), Breggen, R. (Ruud) van der, Doherty, M. (Michael), Felson, D., Gonzalez, A. (Antonio), Halldorsson, B.V. (Bjarni), Hart, D.J. (Deborah), Hauksson, V.B. (Valdimar), Hofman, A. (Albert), Ioannidis, J.P.A. (John), Kloppenburg, M. (Margreet), Lane, N.E. (Nancy), Loughlin, J. (John), Luyten, F.P. (Frank), Nevitt, M.C. (Michael), Parimi, N. (Neeta), Pols, H.A.P. (Huib), Rivadeneira Ramirez, F. (Fernando), Slagboom, P.E. (Eline), Styrkarsdottir, U. (Unnur), Tsezou, A. (Aspasia), Putte, T. (Tom) van de, Zmuda, J. (Joseph), Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Uitterlinden, A.G. (André), Meurs, J.B.J. (Joyce) van, Carr, A.J. (Andrew Jonathan), Kerkhof, J.M. (Hanneke), Lories, R.J. (Rik), Meulenbelt, I. (Ingrid), Jonsdottir, I. (Ingileif), Valdes, A.M. (Ana Maria), Arp, P.P. (Pascal), Ingvarsson, T. (Torvaldur), Jhamai, M. (Mila), Jonsson, H. (Helgi), Stolk, L. (Lisette), Thorleifsson, G. (Gudmar), Zhai, G. (Guangju), Zhang, F. (Feng), Zhu, Y. (Yicheng), Breggen, R. (Ruud) van der, Doherty, M. (Michael), Felson, D., Gonzalez, A. (Antonio), Halldorsson, B.V. (Bjarni), Hart, D.J. (Deborah), Hauksson, V.B. (Valdimar), Hofman, A. (Albert), Ioannidis, J.P.A. (John), Kloppenburg, M. (Margreet), Lane, N.E. (Nancy), Loughlin, J. (John), Luyten, F.P. (Frank), Nevitt, M.C. (Michael), Parimi, N. (Neeta), Pols, H.A.P. (Huib), Rivadeneira Ramirez, F. (Fernando), Slagboom, P.E. (Eline), Styrkarsdottir, U. (Unnur), Tsezou, A. (Aspasia), Putte, T. (Tom) van de, Zmuda, J. (Joseph), Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Uitterlinden, A.G. (André), Meurs, J.B.J. (Joyce) van, and Carr, A.J. (Andrew Jonathan)
Abstract: __Objective__ To identify novel genes involved in osteoarthritis (OA), by means of a genome-wide association study. Methods. We tested 500,510 single-nucleotide polymorphisms (SNPs) in 1,341 Dutch Caucasian OA cases and 3,496 Dutch Caucasian controls. SNPs associated with at least 2 OA phenotypes were analyzed in 14,938 OA cases and ∼39,000 controls. Meta-analyses were performed using the program Comprehensive Meta-analysis, with P values <1 x 10-7considered genomewide significant. __Results__ The C allele of rs3815148 on chromosome 7q22 (minor allele frequency 23%; intron 12 of the COG5 gene) was associated with a 1.14-fold increased risk (95% confidence interval 1.09-1.19) of knee and/or hand OA (P = 8 x 10-8) and also with a 30% increased risk of knee OA progression (95% confidence interval 1.03-1.64) (P = 0.03). This SNP is in almost complete linkage disequilibrium with rs3757713 (68 kb upstream of GPR22), which is associated with GPR22 expression levels in lymphoblast cell lines (P = 4 x 10-12). Immunohistochemistry experiments revealed that G protein-coupled receptor protein 22 (GPR22) was absent in normal mouse articular cartilage or synovium. However, GPR22-positive chondrocytes were found in the upper layers of the articular cartilage of mouse knee joints that were challenged with in vivo papain treatment or methylated bovine serum albumin treatment. GPR22-positive chondrocyte-like cells were also found in osteophytes in instability-induced OA. __Conclusion__ Our findings identify a novel common variant on chromosome 7q22 that influences susceptibility to prevalence and progression of OA. Since the GPR22 gene encodes a G protein-coupled receptor, this is potentially an interesting therapeutic target.
Published: 2010
Full Text: View/download PDF

18. A genome-wide association study suggests that a locus within the ataxin 2 binding protein 1 gene is associated with hand osteoarthritis: The Treat-OA consortium

Author: Zhai, G. (Guangju), Meurs, J.B.J. (Joyce) van, Livshits, G., Meulenbelt, I. (Ingrid), Valdes, A.M., Soranzo, N. (Nicole), Hart, D.J., Zhang, F. (Feng), Kato, B.S., Richards, J.B. (Brent), Williams, F.M.K., Inouye, M., Kloppenburg, M. (Margreet), Demissie, S. (Serkalem), Slagboom, P.E. (Eline), Uitterlinden, A.G. (André), Spector, T.D. (Timothy), Zhai, G. (Guangju), Meurs, J.B.J. (Joyce) van, Livshits, G., Meulenbelt, I. (Ingrid), Valdes, A.M., Soranzo, N. (Nicole), Hart, D.J., Zhang, F. (Feng), Kato, B.S., Richards, J.B. (Brent), Williams, F.M.K., Inouye, M., Kloppenburg, M. (Margreet), Demissie, S. (Serkalem), Slagboom, P.E. (Eline), Uitterlinden, A.G. (André), and Spector, T.D. (Timothy)
Abstract: To identify the susceptibility gene in hand osteoarthritis (OA) the authors used a two-stage approach genomewide association study using two discovery samples (the TwinsUK cohort and the Rotterdam discovery subset; a total of 1804 subjects) and four replication samples (the Chingford Study, the Chuvasha Skeletal Aging Study, the Rotterdam replication subset and the Genetics, Arthrosis, and Progression (GARP) Study; a total of 3266 people). Five single-nucleotide polymorphisms (SNPs) had a likelihood of association with hand OA in the discovery stage and one of them (rs716508), was successfully confirmed in the replication stage (meta-analysis p = 1.81×10-5). The C allele conferred a reduced risk of 33% to 41% using a case-control definition. The SNP is located in intron 1 of the A2BP1 gene. This study also found that the same allele of the SNP significantly reduced bone density at both the hip and spine (p<0.01), suggesting the potential mechanism of the gene in hand OA might be via effects on subchondral bone. The authors' findings provide a potential new insight into genetic mechanisms in the development of hand OA.
Published: 2009
Full Text: View/download PDF

19. Identification of DIO2 as a new susceptibility locus for symptomatic osteoarthritis

Author: Meulenbelt, I. (Ingrid), Min, J. (Josine), Bos, S.D. (Steffan), Riyazi, N. (Naghmeh), Houwing-Duistermaat, J.J. (Jeanine), Wijk, H.J. van der, Kroon, H.M. (Herman), Nakajima, M., Ikegawa, S. (Shiro), Uitterlinden, A.G. (André), Meurs, J.B.J. (Joyce) van, Deure, W.M. (Wendy) van der, Visser, T.J. (Theo), Seymour, A.B. (Albert), Lakenberg, N. (Nico), Breggen, R. (Ruud) van der, Kremer, D. (Dennis), Tikka-Kleemola, P. (Päivi), Kloppenburg, M. (Margreet), Loughlin, J. (John), Slagboom, P.E. (Eline), Meulenbelt, I. (Ingrid), Min, J. (Josine), Bos, S.D. (Steffan), Riyazi, N. (Naghmeh), Houwing-Duistermaat, J.J. (Jeanine), Wijk, H.J. van der, Kroon, H.M. (Herman), Nakajima, M., Ikegawa, S. (Shiro), Uitterlinden, A.G. (André), Meurs, J.B.J. (Joyce) van, Deure, W.M. (Wendy) van der, Visser, T.J. (Theo), Seymour, A.B. (Albert), Lakenberg, N. (Nico), Breggen, R. (Ruud) van der, Kremer, D. (Dennis), Tikka-Kleemola, P. (Päivi), Kloppenburg, M. (Margreet), Loughlin, J. (John), and Slagboom, P.E. (Eline)
Abstract: Osteoarthritis [MIM 165720] is a common late-onset articular joint disease for which no pharmaceutical intervention is available to attenuate the cartilage degeneration. To identify a new osteoarthritis susceptibility locus, a genome-wide linkage scan and combined linkage association analysis were applied to 179 affected siblings and four trios with generalized osteoarthritis (The GARP study). We tested, for confirmation by association, 1478 subjects who required joint replacement and 734 controls in a UK population. Additional replication was tested in 1582 population-based females from the Rotterdam study that contained 94 cases with defined hip osteoarthritis and in 267 Japanese females with symptomatic hip osteoarthritis and 465 controls. Suggested evidence for linkage in the GARP study was observed on chromosome 14q32.11 (log of odds = 3.03, P = 1.9 × 10-4). Genotyping tagging single-nucleotide polymorphisms covering three important candidate genes revealed a common coding variant (rs225014; Thr92Ala) in the iodothyronine-deiodinase enzyme type 2 (D2) gene (DIO2 [MIM 601413]) which significantly explained the linkage signal (P = 0.006). Confirmation and replication by association in the additional osteoarthritis studies indicated a common DIO2 haplotype, exclusively containing the minor allele of rs225014 and common allele of rs12885300, with a combined recessive odds ratio of 1.79, 95% confidence interval (CI) 1.37-2.34 with P = 2.02 × 10-5in female cases with advanced/symptomatic hip osteoarthritis. The gene product of this DIO2 converts intracellular pro-hormone-3,3′,5,5′-tetraiodothyronine (T4) into the active thyroid hormone 3,3′,5-triiodothyronine (T3) thereby regulating intracellular levels of active T3 in target tissues such as the growth plate. Our results indicate a new susceptibility gene (DIO2) conferring risk to osteoarthritis.
Published: 2008
Full Text: View/download PDF

20. Insulin-like growth factor I gene promoter polymorphism, collagen type II alpha1 (COL2A1) gene, and the prevalence of radiographic osteoarthritis: the Rotterdam Study

Author: Zhai, G. (Guangju), Duijn, C.M. (Cornelia) van, Rivadeneira Ramirez, F. (Fernando), Houwing-Duistermaat, J.J. (Jeanine), Meulenbelt, I. (Ingrid), Bijkerk, C. (Casper), Meurs, J.B.J. (Joyce) van, Uitterlinden, A.G. (André), Pols, H.A.P. (Huib), Slagboom, P.E. (Eline), Hofman, A. (Albert), Zhai, G. (Guangju), Duijn, C.M. (Cornelia) van, Rivadeneira Ramirez, F. (Fernando), Houwing-Duistermaat, J.J. (Jeanine), Meulenbelt, I. (Ingrid), Bijkerk, C. (Casper), Meurs, J.B.J. (Joyce) van, Uitterlinden, A.G. (André), Pols, H.A.P. (Huib), Slagboom, P.E. (Eline), and Hofman, A. (Albert)
Abstract: OBJECTIVE: To examine the role of an IGF-I gene promoter polymorphism in the prevalence of radiographic osteoarthritis (ROA), and study its interaction with the COL2A1 gene. METHODS: Individuals genotyped for IGF-I (n = 1546) and COL2A1 gene polymorphisms (n = 808) were selected from a random sample (n = 1583) derived from the Rotterdam study. The presence of ROA was defined as a Kellgren score of 2 or more in at least one of four joints (knee, hip, hand, and spine). Genotype specific odds ratios (OR) were adjusted for age, sex, body mass index, and bone mineral density using logistic regression. Interaction with the COL2A1 genotype was tested. RESULTS: Overall, no association was found between the IGF-I polymorphism and ROA. In subjects aged 65 years or younger (n = 971), the prevalence of ROA increased with the absence of the 192 base pair (bp) allele (p for trend = 0.03). Compared with homozygotes for the 192 bp allele, the prevalence of ROA was 1.4 times higher in heterozygotes (95% confidence interval, 1.0 to 1.8) and 1.9 times higher in non-carriers (1.1 to 3.3). There was evidence of interaction between the IGF-I and COL2A1 genes. Individuals with the risk genotype of both genes had an increased prevalence of ROA (OR 3.4 (1.1 to 10.7)). No effect was observed in subjects older than 65 years. CONCLUSIONS: SUBJECTS: with genetically determined low IGF-I expression (non-carriers of the 192 bp allele) may be at increased risk of ROA before the age of 65 years. Furthermore, an interaction between the IGF-I and COL2A1 genes is suggested.
Published: 2004

21. Heritabilities of radiologic OA in peripheral joins and of disc degeneration of the spine

Author: Bijkerk, C. (Casper), Houwing-Duistermaat, J.J. (Jeanine), Valkenburg, H.A. (Hans), Meulenbelt, I. (Ingrid), Hofman, A. (Albert), Breedveld, F.C. (Ferdinand), Duijn, C.M. (Cornelia) van, Slagboom, P.E. (Eline), Pols, H.A.P. (Huib), Bijkerk, C. (Casper), Houwing-Duistermaat, J.J. (Jeanine), Valkenburg, H.A. (Hans), Meulenbelt, I. (Ingrid), Hofman, A. (Albert), Breedveld, F.C. (Ferdinand), Duijn, C.M. (Cornelia) van, Slagboom, P.E. (Eline), and Pols, H.A.P. (Huib)
Abstract: OBJECTIVE: To estimate the genetic influence on the occurrence of radiologic osteoarthritis (ROA) in the knees, hips, and hands and disc degeneration of the spine in the general population. METHODS: A random sample of 1,583 individuals was drawn to estimate the prevalence of ROA and disc degeneration in the general population. Of 118 probands with multiple affected joint sites who were derived from this sample, we were able to recruit 257 siblings. The variance of ROA and disc degeneration within sibling pairs was compared with the variance between sibling pairs. Heritability estimates for ROA in the knees, hips, and hands and for disc degeneration of the spine were calculated. OA was defined according to radiologic criteria, using the Kellgren/Lawrence grading system. RESULTS: We observed that hand ROA and disc degeneration of the spine were statistically significantly more frequent in siblings than in the random sample, whereas the prevalence of knee and of hip ROA was similar and lower, respectively. Heritability estimates for hand ROA and disc degeneration were statistically significant, P = 0.56 (95% confidence interval [95% CI] 0.34-0.76) and P = 0.75 (95% CI 0.30-1.00), respectively. For knee and hip ROA, no evidence of a genetic effect in the general population was found. Finally, the heritability estimate for a score that summed the number of joints affected in the knees, hips, hands, and spine was 0.78 (95% CI 0.52-0.98). All heritability estimates were adjusted for age, sex, body mass index, and bone mineral density. CONCLUSION: The present study shows that in the general population, there is a strong genetic effect for hand ROA and disc degeneration of the spine. The findings on the total number of joints affected at multiple sites suggest genetic susceptibility to generalized OA.
Published: 1999
Full Text: View/download PDF

22. A genetic association study of the IGF-1 gene and radiological osteoarthritis in a population-based cohort study (the Rotterdam Study)

Author: Meulenbelt, I. (Ingrid), Bijkerk, C. (Casper), Miedema, H.S. (Harald), Breedveld, F.C. (Ferdinand), Valkenburg, H.A. (Hans), Pols, H.A.P. (Huib), Slagboom, P.E. (Eline), Duijn, C.M. (Cornelia) van, Hofman, A. (Albert), Meulenbelt, I. (Ingrid), Bijkerk, C. (Casper), Miedema, H.S. (Harald), Breedveld, F.C. (Ferdinand), Valkenburg, H.A. (Hans), Pols, H.A.P. (Huib), Slagboom, P.E. (Eline), Duijn, C.M. (Cornelia) van, and Hofman, A. (Albert)
Abstract: OBJECTIVE: A genetic association study was performed to investigate whether radiographical osteoarthritis (ROA) was associated with specific genotypes of the insulin-like growth factor I (IGF-1) gene. METHODS: Subjects aged 55-65 years were selected from a population-based study of which ROA at the knee, hip, spine, and hand was assessed. Genotypes were determined of a polymorphism in the promoter region of the IGF-1 gene. RESULTS: The IGF-1 locus was significantly associated with the presence of ROA (over-all adjusted OR for heterozygous subjects = 1.9, 95% CI 1.2, 3.1 and for homozygous subjects 3.6, 95% CI 0.8, 16.2). CONCLUSION: These results suggest that variation at the IGF-1 locus is associated with ROA development and may play a part in ROA pathogenesis. To confirm these findings replication in another population-based sample is needed.
Published: 1998
Full Text: View/download PDF

23. Investigation of the association of the CRTM and CRTL1 genes with radiographically evident osteoarthritis in subjects from the Rotterdam study

Author: Meulenbelt, I. (Ingrid), Bijkerk, C. (Casper), Wildt, S.C.M. de, Miedema, H.S. (Harald), Valkenburg, H.A. (Hans), Breedveld, F.C. (Ferdinand), Pols, H.A.P. (Huib), Te Koppele, J.M. (Johan), Sloos, V.F.G., Hofman, A. (Albert), Slagboom, P.E. (Eline), Duijn, C.M. (Cornelia) van, Meulenbelt, I. (Ingrid), Bijkerk, C. (Casper), Wildt, S.C.M. de, Miedema, H.S. (Harald), Valkenburg, H.A. (Hans), Breedveld, F.C. (Ferdinand), Pols, H.A.P. (Huib), Te Koppele, J.M. (Johan), Sloos, V.F.G., Hofman, A. (Albert), Slagboom, P.E. (Eline), and Duijn, C.M. (Cornelia) van
Abstract: __Objective:__ To investigate whether radiographically evident osteoarthritis (ROA) in 55-65-year-old men and women is associated with specific alleles or genotypes of the cartilage matrix protein (CRTM) and cartilage link protein (CRTLl) genes. __Methods:__ Cases were selected from a populationbased study on the presence of ROA of the knee or hip. Further radiographic analysis included scoring for spine and hand ROA. Controls, selected from the same population, were free of ROA in all joints. __Results:__ The CRTM locus was significantly associated with hip ROA in men (odds ratio 0.50, 95% confidence interval 0.26-0.95). A significant association between ROA and the CRTLl gene was not observed. __Conclusion:__ These results suggest that the CRTM locus may play a role in the sex- and joint site-specific pattern of ROA development.
Published: 1997
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources

Refine your results

23 results on '"Meulenbelt, I. (Ingrid)"'

1. Serum fatty acid chain length associates with prevalent symptomatic end-stage osteoarthritis, independent of BMI

2. Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation

3. Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

4. Genome-wide association and functional studies identify a role for matrix Gla protein in osteoarthritis of the hand

5. Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

6. Translation of clinical problems in osteoarthritis into pathophysiological research goals

7. Associations between joint effusion in the knee and gene expression levels in the circulation: A meta-analysis

8. The transcriptional landscape of age in human peripheral blood

9. Underlying molecular mechanisms of DIO2 susceptibility in symptomatic osteoarthritis

10. Assessment of osteoarthritis candidate genes in a meta-analysis of nine genome-wide association studies

11. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

12. The DOT1L rs12982744 polymorphism is associated with osteoarthritis of the hip with genome-wide statistical significance in males

13. Genome-wide association study meta-analysis of chronic widespread pain: Evidence for involvement of the 5p15.2 region

14. A Meta-Analysis of Thyroid-Related Traits Reveals Novel Loci and Gender-Specific Differences in the Regulation of Thyroid Function

15. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals

16. Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: The TREAT-OA consortium

17. A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22

18. A genome-wide association study suggests that a locus within the ataxin 2 binding protein 1 gene is associated with hand osteoarthritis: The Treat-OA consortium

19. Identification of DIO2 as a new susceptibility locus for symptomatic osteoarthritis

20. Insulin-like growth factor I gene promoter polymorphism, collagen type II alpha1 (COL2A1) gene, and the prevalence of radiographic osteoarthritis: the Rotterdam Study

21. Heritabilities of radiologic OA in peripheral joins and of disc degeneration of the spine

22. A genetic association study of the IGF-1 gene and radiological osteoarthritis in a population-based cohort study (the Rotterdam Study)

23. Investigation of the association of the CRTM and CRTL1 genes with radiographically evident osteoarthritis in subjects from the Rotterdam study

Catalog

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Publication Year Range

Publication Type

Journal

Database

23 results on '"Meulenbelt, I. (Ingrid)"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources