48 results on '"Perry, J.R."'
Search Results
2. PRODIGE: a randomized placebo‐controlled trial of dalteparin low‐molecular‐weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma
- Author
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PERRY, J.R., JULIAN, J.A., LAPERRIERE, N.J., GEERTS, W., AGNELLI, G., ROGERS, L.R., MALKIN, M.G., SAWAYA, R., BAKER, R., FALANGA, A., PARPIA, S., FINCH, T., and LEVINE, M.N.
- Published
- 2010
- Full Text
- View/download PDF
3. Genetic basis of falling risk susceptibility in the UK Biobank Study
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Trajanoska, K., Seppala, L.J., Medina-Gomez, M.C. (Carolina), Hsu, Y.-H. (Yi-Hsiang), Zhou, S.R., Schoor, N.M., Groot, L., Karasik, D. (David), Richards, J.B. (Brent), Kiel, D.P. (Douglas), Uitterlinden, A.G. (André), Perry, J.R. (James), van der Velde, N., Day, F.R. (Felix), Rivadeneira Ramirez, F. (Fernando), Trajanoska, K., Seppala, L.J., Medina-Gomez, M.C. (Carolina), Hsu, Y.-H. (Yi-Hsiang), Zhou, S.R., Schoor, N.M., Groot, L., Karasik, D. (David), Richards, J.B. (Brent), Kiel, D.P. (Douglas), Uitterlinden, A.G. (André), Perry, J.R. (James), van der Velde, N., Day, F.R. (Felix), and Rivadeneira Ramirez, F. (Fernando)
- Published
- 2020
- Full Text
- View/download PDF
4. Tajik Persian
- Author
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Perry, J.R., primary
- Published
- 2006
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- View/download PDF
5. Clonal MET Amplification as a Determinant of Tyrosine Kinase Inhibitor Resistance in Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer
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Lai, Gillianne G.Y., primary, Lim, Tse Hui, additional, Lim, John, additional, Liew, Perry J.R., additional, Kwang, Xue Lin, additional, Nahar, Rahul, additional, Aung, Zaw Win, additional, Takano, Angela, additional, Lee, Yin Yeng, additional, Lau, Dawn P.X., additional, Tan, Gek San, additional, Tan, Sze Huey, additional, Tan, Wan Ling, additional, Ang, Mei-Kim, additional, Toh, Chee Keong, additional, Tan, Bien Soo, additional, Devanand, Anantham, additional, Too, Chow Wei, additional, Gogna, Apoorva, additional, Ong, Boon Hean, additional, Koh, Tina P.T., additional, Kanesvaran, Ravindran, additional, Ng, Quan Sing, additional, Jain, Amit, additional, Rajasekaran, Tanujaa, additional, Yuan, Ju, additional, Lim, Tony Kiat Hon, additional, Lim, Alvin S.T., additional, Hillmer, Axel M., additional, Lim, Wan Teck, additional, Iyer, N. Gopalakrishna, additional, Tam, Wai Leong, additional, Zhai, Weiwei, additional, Tan, Eng-Huat, additional, and Tan, Daniel S.W., additional
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- 2019
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- View/download PDF
6. Impact of a Novel Prioritization Framework on Clinician-Led Oncology Drug Submissions
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Keech, J., primary, Beca, J., additional, Eisen, A., additional, Kennedy, E., additional, Kim, J., additional, Kouroukis, C.T., additional, Darling, G., additional, Ferguson, S.E., additional, Finelli, A., additional, Petrella, T.M., additional, Perry, J.R., additional, Chan, K., additional, and Gavura, S., additional
- Published
- 2019
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7. The Persian Contributions to the English Language: An Historical Dictionary
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Perry, J.R.
- Subjects
The Persian Contributions to the English Language: An Historical Dictionary (Book) -- Book reviews ,Books -- Book reviews - Published
- 2005
8. Is more better? the impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: A secondary analysis of EORTC and NRG Oncology/RTOG
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Blumenthal, D.T. (Deborah T.), Gorlia, T.S. (Thierry), Gilbert, M.R. (Mark R.), Kim, M.M. (Michelle M.), Burt Nabors, L. (L.), Mason, W.P. (Warren), Hegi, M.E. (Monika), Zhang, P. (Peixin), Golfinopoulos, V. (Vassilis), Perry, J.R. (James), Hyun Nam, D. (Do), Erridge, S.C. (Sara C.), Corn, B.W. (Benjamin W.), Mirimanoff, R.O., Brown, P.D. (Paul D), Baumert, B.G. (Brigitta), Mehta, M.P. (Minesh P.), Bent, M.J. (Martin) van den, Reardon, D.A., Weller, M. (Michael), Stupp, R. (Roger), Blumenthal, D.T. (Deborah T.), Gorlia, T.S. (Thierry), Gilbert, M.R. (Mark R.), Kim, M.M. (Michelle M.), Burt Nabors, L. (L.), Mason, W.P. (Warren), Hegi, M.E. (Monika), Zhang, P. (Peixin), Golfinopoulos, V. (Vassilis), Perry, J.R. (James), Hyun Nam, D. (Do), Erridge, S.C. (Sara C.), Corn, B.W. (Benjamin W.), Mirimanoff, R.O., Brown, P.D. (Paul D), Baumert, B.G. (Brigitta), Mehta, M.P. (Minesh P.), Bent, M.J. (Martin) van den, Reardon, D.A., Weller, M. (Michael), and Stupp, R. (Roger)
- Abstract
Background: Radiation with concurrent and adjuvant (6 cycles) temozolomide (TMZ) is the established standard of postsurgical care for newly diagnosed glioblastoma (GBM). This regimen has been adopted with variations, including extending TMZ beyond 6 cycles. The optimal duration of maintenance therapy remains controversial. Methods: We performed pooled analysis of individual patient data from 4 randomized trials for newly diagnosed GBM. All patients who were progression free 28 days after cycle 6 were included. The decision to continue TMZ was per local practice and standards, and at the discretion of the treating physician. Patients were grouped into those treated with 6 cycles and those who continued beyond 6 cycles. Progression-free and overall survival were compared, adjusted by age, performance status, resection extent, and MGMT methylation. Results: A total of 2214 GBM patients were included in the 4 trials. Of these, 624 qualified for analysis 291 continued maintenance TMZ until progression or up to 12 cycles, while 333 discontinued TMZ after 6 cycles. Adjusted for prognostic factors, treatment with more than 6 cycles of TMZ was associated with a somewhat improved progression- free survival (hazard ratio [HR] 0.80 [0.65-0.98], P = .03), in particular for patients with methylated MGMT (n = 342, HR 0.65 [0.50-0.85], P < .01). However, overall survival was not affected by the number of TMZ cycles (HR = 0.92 [0.71-1.19], P = .52), including the MGMT methylated subgroup (HR = 0.89 [0.63-1.26], P = .51). Conclusions: Continuing TMZ beyond 6 cycles was not shown to increase overall survival for newly diagnosed GBM.
- Published
- 2017
- Full Text
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9. Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index
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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
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- 2017
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10. The Neurologic Assessment in Neuro-Oncology (NANO) scale: A tool to assess neurologic function for integration into the Response Assessment in Neuro-Oncology (RANO) criteria
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Nayak, L. (Lakshmi), Deangelis, L.M. (Lisa M.), Brandes, A. (Alba), Peereboom, D.M. (David M.), Galanis, E. (Evanthia), Lin, N.U. (Nancy U), Soffietti, R., MacDonald, D.R. (David R.), Chamberlain, M.C. (Marc C.), Perry, J.R. (James), Jaeckle, K. (K.), Mehta, M.P. (Minesh P.), Stupp, R. (Roger), Muzikansky, A. (Alona), Pentsova, E. (Elena), Cloughesy, T.F. (Timothy F.), Iwamoto, F.M. (Fabio M.), Tonn, J., Vogelbaum, M.A. (Michael), Wen, P.Y. (Patrick), Bent, M.J. (Martin) van den, Reardon, D.A., Nayak, L. (Lakshmi), Deangelis, L.M. (Lisa M.), Brandes, A. (Alba), Peereboom, D.M. (David M.), Galanis, E. (Evanthia), Lin, N.U. (Nancy U), Soffietti, R., MacDonald, D.R. (David R.), Chamberlain, M.C. (Marc C.), Perry, J.R. (James), Jaeckle, K. (K.), Mehta, M.P. (Minesh P.), Stupp, R. (Roger), Muzikansky, A. (Alona), Pentsova, E. (Elena), Cloughesy, T.F. (Timothy F.), Iwamoto, F.M. (Fabio M.), Tonn, J., Vogelbaum, M.A. (Michael), Wen, P.Y. (Patrick), Bent, M.J. (Martin) van den, and Reardon, D.A.
- Abstract
__Background__ The Macdonald criteria and the Response Assessment in Neuro-Oncology (RANO) criteria defne radiologic parameters to classify therapeutic outcome among patients with malignant glioma and specify that clinical status must be incorporated and prioritized for overall assessment. But neither provides specifc parameters to do so. We hypothesized that a standardized metric to measure neurologic function will permit more effective overall response assessment in neuro-oncology. __Methods__ An international group of physicians including neurologists, medical oncologists, radiation oncologists, and neurosurgeons with expertise in neuro-oncology drafted the Neurologic Assessment in Neuro-Oncology (NANO) scale as an objective and quantifable metric of neurologic function evaluable during a routine offce examination. The scale was subsequently tested in a multicenter study to determine its overall reliability, interobserver variability, and feasibility. __Results__ The NANO scale is a quantifable evaluation of 9 relevant neurologic domains based on direct observation and testing conducted during routine offce visits. The score defnes overall response criteria. A prospective, multinational study noted a >90% inter-observer agreement rate with kappa statistic ranging from 0.35 to 0.83 (fair to almost perfect agreement), and a median assessment time of 4 minutes (interquartile range, 3-5). __Conclusion__ The NANO scale provides an objective clinician-reported outcome of neurologic function with high inter-observer agreement. It is designed to combine with radiographic assessment to provide an overall assessment of outcome for neuro-oncology patients in clinical trials and in daily practice. Furthermore, it complements existing patient-reported outcomes and cognition testing to combine for a global clinical outcome assessment of well-being among brain tumor patients.
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- 2017
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11. Corrigendum: Rare coding variants and X-linked loci associated with age at menarche
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Lunetta, K.L., Day, F.R., Sulem, P., Ruth, K.S., Tung, J.Y., Hinds, D.A., Esko, T., Elks, C.E., Altmaier, E., He, C., Huffman, J.E., Mihailov, E., Porcu, E., Robino, A., Rose, L.M., Schick, U.M., Stolk, L., Teumer, A., Thompson, D.J., Traglia, M., Wang, C.A., Yerges-Armstrong, L.M., Antoniou, A.C., Barbieri, C., Coviello, A.D., Cucca, F., Demerath, E.W., Dunning, A.M., Gandin, I., Grove, M.L., Gudbjartsson, D.F., Hocking, L.J., Hofman, A., Huang, J., Jackson, R.D., Karasik, D., Kriebel, J., Lange, E.M., Lange, L.A., Langenberg, C., Li, X., Luan, J., Mägi, R., Morrison, A.C., Padmanabhan, S., Pirie, A., Polasek, O., Porteous, D.J., Reiner, A.P., Rivadeneira, F., Rudan, I., Sala, C.F., Schlessinger, D., Scott, R.A., Stöckl, D., Visser, J.A., Völker, U., Vozzi, D., Wilson, J.G., Zygmunt, M., EPIC-Interact Consortium (), Generation Scotland Consortium (), Boerwinkle, E., Buring, J.E., Crisponi, L., Easton, D.F., Hayward, C., Hu, F.B., Liu, S., Metspalu, A., Pennell, C.E., Ridker, P.M., Strauch, K., Streeten, E.A., Toniolo, D., Uitterlinden, A.G., Ulivi, S., Völzke, H., Wareham, N.J., Wellons, M., Franceschini, N., Chasman, D.I., Thorsteinsdottir, U., Murray, A., Stefansson, K., Murabito, J.M., Ong, K.K., and Perry, J.R.
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Adult ,Adolescent ,Genotype ,Mutation, Missense ,Immunoglobulins ,Cell Cycle Proteins ,Penetrance ,AMP-Activated Protein Kinases ,Autoantigens ,White People ,Young Adult ,Gene Frequency ,Genes, X-Linked ,Humans ,Aged ,Menarche ,Chromosomes, Human, X ,Hypogonadism ,Fatty Acids ,Age Factors ,Genetic Variation ,Membrane Proteins ,Proteins ,RNA-Binding Proteins ,Receptors, Neurokinin-3 ,Middle Aged ,Corrigenda ,Amides ,Phenotype ,Codon, Nonsense ,Female ,RNA Interference ,Laminin ,Energy Metabolism ,Signal Transduction - Abstract
More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ∼3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P5 × 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P=9.4 × 10(-13)) and FAAH2 (rs5914101, P=4.9 × 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P=2.8 × 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ∼0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.
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- 2015
12. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals
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Dastani, Z., Hivert, M.f., Timpson, N., Perry, J.r., Yuan, X., Scott, R.a., Henneman, P., Heid, I.m., Bravenboer, Bert, and Clinical sciences
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meta-analysis ,type 2 diabetes ,metabolic traits - 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
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- 2014
13. PS1 - 160 A Telephone Based Cognitive Assessment Tool for Brain Metastases Patients
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Tsao, M.N., primary, Edelstein, K., additional, Bernstein, L.J., additional, Wong, J., additional, Laperriere, N., additional, Perry, J.R., additional, Sahgal, A., additional, Menard, C., additional, Soliman, H., additional, Chow, E., additional, Barnes, T., additional, Danjoux, C., additional, Millar, B.A., additional, Wong, R., additional, Wells, W., additional, McIntyre, R.S., additional, Mason, W., additional, and Chung, C., additional
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- 2016
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14. New genetic loci link adipose and insulin biology to body fat distribution.
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ADIPOGen Consortium, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, International Endogene Consortium, LifeLines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium, ReproGen Consortium, GLGC, ICBP, Dastani, Z., Hivert, MF., Timpson, N., Perry, JR., Yuan, X., Scott, RA., Henneman, P., Heid, IM., Kizer, JR., Lyytikainen, LP., Fuchsberger, C., Tanaka, T., Morris, AP., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, JS., Uh, HW., Wu, Y., Bidulescu, A., Rasmussen-Torvik, LJ., Greenwood, CM., Ladouceur, M., Grimsby, J., Manning, AK., Liu, CT., Kooner, J., Mooser, VE., Vollenweider, P., Kapur, KA., Chambers, J., Wareham, NJ., Langenberg, C., Frants, R., Willemsvan-vanDijk, K., Oostra, BA., Willems, SM., Lamina, C., Winkler, T., Psaty, BM., Tracy, RP., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, PP., Evans, DM., St Pourcain, B., Sattar, N., Wood, A., Bandinelli, S., Carlson, OD., 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- Abstract
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
- Published
- 2015
15. Directional dominance on stature and cognition in diverse human populations.
- Author
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BioBank Japan, Project, Joshi, P.K., Esko, T., Mattsson, H., Eklund, N., Gandin, I., Nutile, T., Jackson, A.U., Schurmann, C., Smith, A.V., Zhang, W., Okada, Y., Stančáková, A., Faul, J.D., Zhao, W., Bartz, T.M., Concas, M.P., Franceschini, N., Enroth, S., Vitart, V., Trompet, S., Guo, X., Chasman, D.I., O'Connel, J.R., Corre, T., Nongmaithem, S.S., Chen, Y., Mangino, M., Ruggiero, D., Traglia, M., Farmaki, A.E., Kacprowski, T., Bjonnes, A., van der Spek, A., Wu, Y., Giri, A.K., Yanek, L.R., Wang, L., Hofer, E., Rietveld, C.A., McLeod, O., Cornelis, M.C., Pattaro, C., Verweij, N., Baumbach, C., Abdellaoui, A., Warren, H.R., Vuckovic, D., Mei, H., Bouchard, C., Perry, J.R., Cappellani, S., Mirza, S.S., Benton, M.C., Broeckel, U., Medland, S.E., Lind, P.A., Malerba, G., Drong, A., Yengo, L., Bielak, L.F., Zhi, D., van der Most, P.J., Shriner, D., Mägi, R., Hemani, G., Karaderi, T., Wang, Z., Liu, T., Demuth, I., Zhao, J.H., Meng, W., Lataniotis, L., van der Laan, S.W., Bradfield, J.P., Wood, A.R., Bonnefond, A., Ahluwalia, T.S., Hall, L.M., Salvi, E., Yazar, S., Carstensen, L., de Haan, H.G., Abney, M., Afzal, U., Allison, M.A., Amin, N., Asselbergs, F.W., Bakker, S.J., Barr, R.G., Baumeister, S.E., Benjamin, D.J., Bergmann, S., Boerwinkle, E., Bottinger, E.P., Campbell, A., Chakravarti, A., Chan, Y., Chanock, S.J., Chen, C., Chen, Y.D., Collins, F.S., Connell, J., Correa, A., Cupples, L.A., Smith, G.D., Davies, G., Dörr, M., Ehret, G., Ellis, S.B., Feenstra, B., Feitosa, M.F., Ford, I., Fox, C.S., Frayling, T.M., Friedrich, N., Geller, F., Scotland, G., Gillham-Nasenya, I., Gottesman, O., Graff, M., Grodstein, F., Gu, C., Haley, C., Hammond, C.J., Harris, S.E., Harris, T.B., Hastie, N.D., Heard-Costa, N.L., Heikkilä, K., Hocking, L.J., Homuth, G., Hottenga, J.J., Huang, J., Huffman, J.E., Hysi, P.G., Ikram, M.A., Ingelsson, E., Joensuu, A., Johansson, Å., Jousilahti, P., Jukema, J.W., Kähönen, M., Kamatani, Y., Kanoni, S., Kerr, S.M., Khan, N.M., Koellinger, P., Koistinen, H.A., Kooner, M.K., Kubo, M., Kuusisto, J., Lahti, J., Launer, L.J., Lea, R.A., Lehne, B., Lehtimäki, T., Liewald, D.C., Lind, L., Loh, M., Lokki, M.L., London, S.J., Loomis, S.J., Loukola, A., Lu, Y., Lumley, T., Lundqvist, A., Männistö, S., Marques-Vidal, P., Masciullo, C., Matchan, A., Mathias, R.A., Matsuda, K., Meigs, J.B., Meisinger, C., Meitinger, T., Menni, C., Mentch, F.D., Mihailov, E., Milani, L., Montasser, M.E., Montgomery, G.W., Morrison, A., Myers, R.H., Nadukuru, R., Navarro, P., Nelis, M., Nieminen, M.S., Nolte, I.M., O'Connor, G.T., Ogunniyi, A., Padmanabhan, S., Palmas, W.R., Pankow, J.S., Patarcic, I., Pavani, F., Peyser, P.A., Pietilainen, K., Poulter, N., Prokopenko, I., Ralhan, S., Redmond, P., Rich, S.S., Rissanen, H., Robino, A., Rose, L.M., Rose, R., Sala, C., Salako, B., Salomaa, V., Sarin, A.P., Saxena, R., Schmidt, H., Scott, L.J., Scott, W.R., Sennblad, B., Seshadri, S., Sever, P., Shrestha, S., Smith, B.H., Smith, J.A., Soranzo, N., 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N.G., Hunt, S.C., Starr, J.M., Deary, I.J., Griffiths, L.R., Tiemeier, H., Pirastu, N., Kaprio, J., Wareham, N.J., Pérusse, L., Wilson, J.G., Girotto, G., Caulfield, M.J., Raitakari, O., Boomsma, D.I., Gieger, C., van der Harst, P., Hicks, A.A., Kraft, P., Sinisalo, J., Knekt, P., Johannesson, M., Magnusson, P.K., Hamsten, A., Schmidt, R., Borecki, I.B., Vartiainen, E., Becker, D.M., Bharadwaj, D., Mohlke, K.L., Boehnke, M., van Duijn, C.M., Sanghera, D.K., Teumer, A., Zeggini, E., Metspalu, A., Gasparini, P., Ulivi, S., Ober, C., Toniolo, D., Rudan, I., Porteous, D.J., Ciullo, M., Spector, T.D., Hayward, C., Dupuis, J., Loos, R.J., Wright, A.F., Chandak, G.R., Vollenweider, P., Shuldiner, A.R., Ridker, P.M., Rotter, J.I., Sattar, N., Gyllensten, U., North, K.E., Pirastu, M., Psaty, B.M., Weir, D.R., Laakso, M., Gudnason, V., Takahashi, A., Chambers, J.C., Kooner, J.S., Strachan, D.P., Campbell, H., Hirschhorn, J.N., Perola, M., Pola?ek O., Wilson, J.F., BioBank Japan, Project, Joshi, P.K., Esko, T., Mattsson, H., Eklund, N., Gandin, I., Nutile, T., Jackson, A.U., Schurmann, C., Smith, A.V., Zhang, W., Okada, Y., Stančáková, A., Faul, J.D., Zhao, W., Bartz, T.M., Concas, M.P., Franceschini, N., Enroth, S., Vitart, V., Trompet, S., Guo, X., Chasman, D.I., O'Connel, J.R., Corre, T., Nongmaithem, S.S., Chen, Y., Mangino, M., Ruggiero, D., Traglia, M., Farmaki, A.E., Kacprowski, T., Bjonnes, A., van der Spek, A., Wu, Y., Giri, A.K., Yanek, L.R., Wang, L., Hofer, E., Rietveld, C.A., McLeod, O., Cornelis, M.C., Pattaro, C., Verweij, N., Baumbach, C., Abdellaoui, A., Warren, H.R., Vuckovic, D., Mei, H., Bouchard, C., Perry, J.R., Cappellani, S., Mirza, S.S., Benton, M.C., Broeckel, U., Medland, S.E., Lind, P.A., Malerba, G., Drong, A., Yengo, L., Bielak, L.F., Zhi, D., van der Most, P.J., Shriner, D., Mägi, R., Hemani, G., Karaderi, T., Wang, Z., Liu, T., Demuth, I., Zhao, J.H., Meng, W., Lataniotis, L., van der Laan, S.W., Bradfield, J.P., Wood, A.R., Bonnefond, A., Ahluwalia, T.S., Hall, L.M., Salvi, E., Yazar, S., Carstensen, L., de Haan, H.G., Abney, M., Afzal, U., Allison, M.A., Amin, N., Asselbergs, F.W., Bakker, S.J., Barr, R.G., Baumeister, S.E., Benjamin, D.J., Bergmann, S., Boerwinkle, E., Bottinger, E.P., Campbell, A., Chakravarti, A., Chan, Y., Chanock, S.J., Chen, C., Chen, Y.D., Collins, F.S., Connell, J., Correa, A., Cupples, L.A., Smith, G.D., Davies, G., Dörr, M., Ehret, G., Ellis, S.B., Feenstra, B., Feitosa, M.F., Ford, I., Fox, C.S., Frayling, T.M., Friedrich, N., Geller, F., Scotland, G., Gillham-Nasenya, I., Gottesman, O., Graff, M., Grodstein, F., Gu, C., Haley, C., Hammond, C.J., Harris, S.E., Harris, T.B., Hastie, N.D., Heard-Costa, N.L., Heikkilä, K., Hocking, L.J., Homuth, G., Hottenga, J.J., Huang, J., Huffman, J.E., Hysi, P.G., Ikram, M.A., Ingelsson, E., Joensuu, A., Johansson, Å., Jousilahti, P., Jukema, J.W., Kähönen, M., Kamatani, Y., Kanoni, S., Kerr, S.M., Khan, N.M., Koellinger, P., Koistinen, H.A., Kooner, M.K., Kubo, M., Kuusisto, J., Lahti, J., Launer, L.J., Lea, R.A., Lehne, B., Lehtimäki, T., Liewald, D.C., Lind, L., Loh, M., Lokki, M.L., London, S.J., Loomis, S.J., Loukola, A., Lu, Y., Lumley, T., Lundqvist, A., Männistö, S., Marques-Vidal, P., Masciullo, C., Matchan, A., Mathias, R.A., Matsuda, K., Meigs, J.B., Meisinger, C., Meitinger, T., Menni, C., Mentch, F.D., Mihailov, E., Milani, L., Montasser, M.E., Montgomery, G.W., Morrison, A., Myers, R.H., Nadukuru, R., Navarro, P., Nelis, M., Nieminen, M.S., Nolte, I.M., O'Connor, G.T., Ogunniyi, A., Padmanabhan, S., Palmas, W.R., Pankow, J.S., Patarcic, I., Pavani, F., Peyser, P.A., Pietilainen, K., Poulter, N., Prokopenko, I., Ralhan, S., Redmond, P., Rich, S.S., Rissanen, H., Robino, A., Rose, L.M., Rose, R., Sala, C., Salako, B., Salomaa, V., Sarin, A.P., Saxena, R., Schmidt, H., Scott, L.J., Scott, W.R., Sennblad, B., Seshadri, S., Sever, P., Shrestha, S., Smith, B.H., Smith, J.A., Soranzo, N., Sotoodehnia, N., Southam, L., Stanton, A.V., Stathopoulou, M.G., Strauch, K., Strawbridge, R.J., Suderman, M.J., Tandon, N., Tang, S.T., Taylor, K.D., Tayo, B.O., Töglhofer, A.M., Tomaszewski, M., T?ernikova N., Tuomilehto, J., Uitterlinden, A.G., Vaidya, D., van Hylckama Vlieg, A., van Setten, J., Vasankari, T., Vedantam, S., Vlachopoulou, E., Vozzi, D., Vuoksimaa, E., Waldenberger, M., Ware, E.B., Wentworth-Shields, W., Whitfield, J.B., Wild, S., Willemsen, G., Yajnik, C.S., Yao, J., Zaza, G., Zhu, X., Salem, R.M., Melbye, M., Bisgaard, H., Samani, N.J., Cusi, D., Mackey, D.A., Cooper, R.S., Froguel, P., Pasterkamp, G., Grant, S.F., Hakonarson, H., Ferrucci, L., Scott, R.A., Morris, A.D., Palmer, C.N., Dedoussis, G., Deloukas, P., Bertram, L., Lindenberger, U., Berndt, S.I., Lindgren, C.M., Timpson, N.J., Tönjes, A., Munroe, P.B., Sørensen, T.I., Rotimi, C.N., Arnett, D.K., Oldehinkel, A.J., Kardia, S.L., Balkau, B., Gambaro, G., Morris, A.P., Eriksson, J.G., Wright, M.J., Martin, N.G., Hunt, S.C., Starr, J.M., Deary, I.J., Griffiths, L.R., Tiemeier, H., Pirastu, N., Kaprio, J., Wareham, N.J., Pérusse, L., Wilson, J.G., Girotto, G., Caulfield, M.J., Raitakari, O., Boomsma, D.I., Gieger, C., van der Harst, P., Hicks, A.A., Kraft, P., Sinisalo, J., Knekt, P., Johannesson, M., Magnusson, P.K., Hamsten, A., Schmidt, R., Borecki, I.B., Vartiainen, E., Becker, D.M., Bharadwaj, D., Mohlke, K.L., Boehnke, M., van Duijn, C.M., Sanghera, D.K., Teumer, A., Zeggini, E., Metspalu, A., Gasparini, P., Ulivi, S., Ober, C., Toniolo, D., Rudan, I., Porteous, D.J., Ciullo, M., Spector, T.D., Hayward, C., Dupuis, J., Loos, R.J., Wright, A.F., Chandak, G.R., Vollenweider, P., Shuldiner, A.R., Ridker, P.M., Rotter, J.I., Sattar, N., Gyllensten, U., North, K.E., Pirastu, M., Psaty, B.M., Weir, D.R., Laakso, M., Gudnason, V., Takahashi, A., Chambers, J.C., Kooner, J.S., Strachan, D.P., Campbell, H., Hirschhorn, J.N., Perola, M., Pola?ek O., and Wilson, J.F.
- Abstract
Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolu
- Published
- 2015
16. 26LBA Does valproic acid improve survival in glioblastoma? A meta-analysis of randomized trials in newly diagnosed glioblastoma
- Author
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Happold, C., primary, Gorlia, T., additional, Chinot, O., additional, Gilbert, M., additional, Nabors, L.B., additional, Wick, W., additional, Pugh, S.L., additional, Hegi, M., additional, Cloughesy, T., additional, Roth, P., additional, Reardon, D.A., additional, Perry, J.R., additional, Mehta, M.P., additional, Stupp, R., additional, and Weller, M., additional
- Published
- 2015
- Full Text
- View/download PDF
17. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche
- Author
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Perry, J.R., Day, F., Elks, C.E., Sulem, P., Thompson, D.J., Ferreira, T., He, C., Chasman, D.I., Esko, T., Thorleifsson, G., Albrecht, E., Ang, W.Q., Corre, T., Cousminer, D.L., Feenstra, B., Franceschini, N., Ganna, A., Johnson, A.D., Kjellqvist, S., Lunetta, K.L., McMahon, G., Nolte, I.M., Paternoster, L., Porcu, E., Smith, A.V., Stolk, L., Teumer, A., Tsernikova, N., Tikkanen, E., Ulivi, S., Wagner, E.K., Amin, N., Bierut, L.J., Byrne, E.M., Hottenga, J.J., Koller, D.L., Mangino, M., Pers, T.H., Yerges-Armstrong, L.M., Zhao, J., Andrulis, I.L., Anton-Culver, H., Atsma, F., Bandinelli, S., Beckmann, M.W., Benitez, J., Blomqvist, C., Bojesen, S.E., Bolla, M.K., Bonanni, B., Brauch, H., Brenner, H., Buring, J.E., Chang-Claude, J., Chanock, S., Chen, J., Chenevix-Trench, G., Collee, J.M., Couch, F.J., Couper, D., Coviello, A.D., Cox, A, Czene, K., D'Adamo, P., Smith, G., Vivo, I. De, Demerath, E.W., Dennis, J., Devilee, P., Dieffenbach, A.K., Dunning, A.M., Eiriksdottir, G., Eriksson, J.G., Fasching, P.A., Ferrucci, L., Flesch-Janys, D., Flyger, H., Foroud, T., Franke, L., Garcia, M.E., Garcia-Closas, M., Geller, F., Geus, E.E. de, Giles, G.G., Gudbjartsson, D.F., Gudnason, V., Guenel, P., Guo, S., Hall, P., Hamann, U., Haring, R., Hartman, C.A., Heath, A.C., Hofman, A., Hooning, M.J., Hopper, J.L., Hu, F.B., Hunter, D.J., Karasik, D., Kiel, D.P., et al., Perry, J.R., Day, F., Elks, C.E., Sulem, P., Thompson, D.J., Ferreira, T., He, C., Chasman, D.I., Esko, T., Thorleifsson, G., Albrecht, E., Ang, W.Q., Corre, T., Cousminer, D.L., Feenstra, B., Franceschini, N., Ganna, A., Johnson, A.D., Kjellqvist, S., Lunetta, K.L., McMahon, G., Nolte, I.M., Paternoster, L., Porcu, E., Smith, A.V., Stolk, L., Teumer, A., Tsernikova, N., Tikkanen, E., Ulivi, S., Wagner, E.K., Amin, N., Bierut, L.J., Byrne, E.M., Hottenga, J.J., Koller, D.L., Mangino, M., Pers, T.H., Yerges-Armstrong, L.M., Zhao, J., Andrulis, I.L., Anton-Culver, H., Atsma, F., Bandinelli, S., Beckmann, M.W., Benitez, J., Blomqvist, C., Bojesen, S.E., Bolla, M.K., Bonanni, B., Brauch, H., Brenner, H., Buring, J.E., Chang-Claude, J., Chanock, S., Chen, J., Chenevix-Trench, G., Collee, J.M., Couch, F.J., Couper, D., Coviello, A.D., Cox, A, Czene, K., D'Adamo, P., Smith, G., Vivo, I. De, Demerath, E.W., Dennis, J., Devilee, P., Dieffenbach, A.K., Dunning, A.M., Eiriksdottir, G., Eriksson, J.G., Fasching, P.A., Ferrucci, L., Flesch-Janys, D., Flyger, H., Foroud, T., Franke, L., Garcia, M.E., Garcia-Closas, M., Geller, F., Geus, E.E. de, Giles, G.G., Gudbjartsson, D.F., Gudnason, V., Guenel, P., Guo, S., Hall, P., Hamann, U., Haring, R., Hartman, C.A., Heath, A.C., Hofman, A., Hooning, M.J., Hopper, J.L., Hu, F.B., Hunter, D.J., Karasik, D., Kiel, D.P., and et al.
- Abstract
Contains fulltext : 136472.pdf (publisher's version ) (Closed access), Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.
- Published
- 2014
18. Simplified Grammar of Arabic, Persian, and Hindustani
- Author
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Perry, J.R.
- Subjects
Simplified Grammar of Arabic, Persian, and Hindustani (Book) -- Book reviews ,Books -- Book reviews - Published
- 2006
19. Fables of the Ancients? Folklore in the Quran
- Author
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Perry, J.R.
- Subjects
Fables of the Ancients?: Folklore in the Qur'an(Book) -- Book reviews ,Books -- Book reviews - Published
- 2006
20. Directional dominance on stature and cognition in diverse human populations
- Author
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Joshi, P.K., Esko, T., Mattsson, H., Eklund, N., Gandin, I., Nutile, T., Jackson, A.U., Schurmann, C., Smith, A.V., Zhang, W., Okada, Y., Stančáková, A., Faul, J.D., Zhao, W., Bartz, T.M., Concas, M.P., Franceschini, N., Enroth, S., Vitart, V., Trompet, S., Guo, X., Chasman, D.I., O'Connel, J.R., Corre, T., Nongmaithem, S.S., Chen, Y., Mangino, M., Ruggiero, D., Traglia, M., Farmaki, A.E., Kacprowski, T., Bjonnes, A., van der Spek, A., Wu, Y., Giri, A.K., Yanek, L.R., Wang, L., Hofer, E., Rietveld, C.A., McLeod, O., Cornelis, M.C., Pattaro, C., Verweij, N., Baumbach, C., Abdellaoui, A., Warren, H.R., Vuckovic, D., Mei, H., Bouchard, C., Perry, J.R., Cappellani, S., Mirza, S.S., Benton, M.C., Broeckel, U., Medland, S.E., Lind, P.A., Malerba, G., Drong, A., Yengo, L., Bielak, L.F., Zhi, D., van der Most, P.J., Shriner, D., Mägi, R., Hemani, G., Karaderi, T., Wang, Z., Liu, T., Demuth, I., Zhao, J.H., Meng, W., Lataniotis, L., van der Laan, S.W., Bradfield, J.P., Wood, A.R., Bonnefond, A., Ahluwalia, T.S., Hall, L.M., Salvi, E., Yazar, S., Carstensen, L., de Haan, H.G., Abney, M., Afzal, U., Allison, M.A., Amin, N., Asselbergs, F.W., Bakker, S.J., Barr, R.G., Baumeister, S.E., Benjamin, D.J., Bergmann, S., Boerwinkle, E., Bottinger, E.P., Campbell, A., Chakravarti, A., Chan, Y., Chanock, S.J., Chen, C., Chen, Y.D., Collins, F.S., Connell, J., Correa, A., Cupples, L.A., Smith, G.D., Davies, G., Dörr, M., Ehret, G., Ellis, S.B., Feenstra, B., Feitosa, M.F., Ford, I., Fox, C.S., Frayling, T.M., Friedrich, N., Geller, F., Scotland, G., Gillham-Nasenya, I., Gottesman, O., Graff, M., Grodstein, F., Gu, C., Haley, C., Hammond, C.J., Harris, S.E., Harris, T.B., Hastie, N.D., Heard-Costa, N.L., Heikkilä, K., Hocking, L.J., Homuth, G., Hottenga, J.J., Huang, J., Huffman, J.E., Hysi, P.G., Ikram, M.A., Ingelsson, E., Joensuu, A., Johansson, Å., Jousilahti, P., Jukema, J.W., Kähönen, M., Kamatani, Y., Kanoni, S., Kerr, S.M., Khan, N.M., Koellinger, P., Koistinen, H.A., Kooner, M.K., Kubo, M., Kuusisto, J., Lahti, J., Launer, L.J., Lea, R.A., Lehne, B., Lehtimäki, T., Liewald, D.C., Lind, L., Loh, M., Lokki, M.L., London, S.J., Loomis, S.J., Loukola, A., Lu, Y., Lumley, T., Lundqvist, A., Männistö, S., Marques-Vidal, P., Masciullo, C., Matchan, A., Mathias, R.A., Matsuda, K., Meigs, J.B., Meisinger, C., Meitinger, T., Menni, C., Mentch, F.D., Mihailov, E., Milani, L., Montasser, M.E., Montgomery, G.W., Morrison, A., Myers, R.H., Nadukuru, R., Navarro, P., Nelis, M., Nieminen, M.S., Nolte, I.M., O'Connor, G.T., Ogunniyi, A., Padmanabhan, S., Palmas, W.R., Pankow, J.S., Patarcic, I., Pavani, F., Peyser, P.A., Pietilainen, K., Poulter, N., Prokopenko, I., Ralhan, S., Redmond, P., Rich, S.S., Rissanen, H., Robino, A., Rose, L.M., Rose, R., Sala, C., Salako, B., Salomaa, V., Sarin, A.P., Saxena, R., Schmidt, H., Scott, L.J., Scott, W.R., Sennblad, B., Seshadri, S., Sever, P., Shrestha, S., Smith, B.H., Smith, J.A., Soranzo, N., Sotoodehnia, N., Southam, L., Stanton, A.V., Stathopoulou, M.G., Strauch, K., Strawbridge, R.J., Suderman, M.J., Tandon, N., Tang, S.T., Taylor, K.D., Tayo, B.O., Töglhofer, A.M., Tomaszewski, M., T?ernikova N., Tuomilehto, J., Uitterlinden, A.G., Vaidya, D., van Hylckama Vlieg, A., van Setten, J., Vasankari, T., Vedantam, S., Vlachopoulou, E., Vozzi, D., Vuoksimaa, E., Waldenberger, M., Ware, E.B., Wentworth-Shields, W., Whitfield, J.B., Wild, S., Willemsen, G., Yajnik, C.S., Yao, J., Zaza, G., Zhu, X., BioBank Japan, Project, Salem, R.M., Melbye, M., Bisgaard, H., Samani, N.J., Cusi, D., Mackey, D.A., Cooper, R.S., Froguel, P., Pasterkamp, G., Grant, S.F., Hakonarson, H., Ferrucci, L., Scott, R.A., Morris, A.D., Palmer, C.N., Dedoussis, G., Deloukas, P., Bertram, L., Lindenberger, U., Berndt, S.I., Lindgren, C.M., Timpson, N.J., Tönjes, A., Munroe, P.B., Sørensen, T.I., Rotimi, C.N., Arnett, D.K., Oldehinkel, A.J., Kardia, S.L., Balkau, B., Gambaro, G., Morris, A.P., Eriksson, J.G., Wright, M.J., Martin, N.G., Hunt, S.C., Starr, J.M., Deary, I.J., Griffiths, L.R., Tiemeier, H., Pirastu, N., Kaprio, J., Wareham, N.J., Pérusse, L., Wilson, J.G., Girotto, G., Caulfield, M.J., Raitakari, O., Boomsma, D.I., Gieger, C., van der Harst, P., Hicks, A.A., Kraft, P., Sinisalo, J., Knekt, P., Johannesson, M., Magnusson, P.K., Hamsten, A., Schmidt, R., Borecki, I.B., Vartiainen, E., Becker, D.M., Bharadwaj, D., Mohlke, K.L., Boehnke, M., van Duijn, C.M., Sanghera, D.K., Teumer, A., Zeggini, E., Metspalu, A., Gasparini, P., Ulivi, S., Ober, C., Toniolo, D., Rudan, I., Porteous, D.J., Ciullo, M., Spector, T.D., Hayward, C., Dupuis, J., Loos, R.J., Wright, A.F., Chandak, G.R., Vollenweider, P., Shuldiner, A.R., Ridker, P.M., Rotter, J.I., Sattar, N., Gyllensten, U., North, K.E., Pirastu, M., Psaty, B.M., Weir, D.R., Laakso, M., Gudnason, V., Takahashi, A., Chambers, J.C., Kooner, J.S., Strachan, D.P., Campbell, H., Hirschhorn, J.N., Perola, M., Pola?ek O., Wilson, J.F., Immunology, Medical Microbiology & Infectious Diseases, Erasmus MC other, Medical Informatics, Epidemiology, Pathology, Public Health, Ophthalmology, Internal Medicine, Cardiology, Child and Adolescent Psychiatry / Psychology, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Joshi, Peter K, Esko, Tonu, Mattsson, Hannele, Eklund, Niina, Gandin, Ilaria, Nutile, Teresa, Jackson, Anne U., Schurmann, Claudia, Smith, Albert V., Zhang, Weihua, Okada, Yukinori, Stančáková, Alena, Faul, Jessica D., Zhao, Wei, Bartz, Traci M., Concas, MARIA PINA, Franceschini, Nora, Enroth, Stefan, Vitart, Veronique, Trompet, Stella, Guo, Xiuqing, Chasman, Daniel I., O'Connel, Jeffrey R., Corre, Tanguy, Nongmaithem, Suraj S., Chen, Yuning, Mangino, Massimo, Ruggiero, Daniela, Traglia, Michela, Farmaki, Aliki Eleni, Kacprowski, Tim, Bjonnes, Andrew, Van Der Spek, Ashley, Wu, Ying, Giri, Anil K., Yanek, Lisa R., Wang, Lihua, Hofer, Edith, Rietveld, Cornelius A., Mcleod, Olga, Cornelis, Marilyn C., Pattaro, Cristian, Verweij, Niek, Baumbach, Clemen, Abdellaoui, Abdel, Warren, Helen R., Vuckovic, Dragana, Mei, Hao, Bouchard, Claude, Perry, John R. B., Cappellani, Stefania, Mirza, Saira S., Benton, Miles C., Broeckel, Ulrich, Medland, Sarah E., Lind, Penelope A., Malerba, Giovanni, Drong, Alexander, Yengo, Loic, Bielak, Lawrence F., Zhi, Degui, Van Der Most, Peter J., Shriner, Daniel, Mägi, Reedik, Hemani, Gibran, Karaderi, Tugce, Wang, Zhaoming, Liu, Tian, Demuth, Ilja, Zhao, Jing Hua, Meng, Weihua, Lataniotis, Lazaro, Van Der Laan, Sander W., Bradfield, Jonathan P., Wood, Andrew R., Bonnefond, Amelie, Ahluwalia, Tarunveer S., Hall, Leanne M., Salvi, Erika, Yazar, Seyhan, Carstensen, Lisbeth, De Haan, Hugoline G., Abney, Mark, Afzal, Uzma, Allison, Matthew A., Amin, Najaf, Asselbergs, Folkert W., Bakker, Stephan J. L., Barr, R. Graham, Baumeister, Sebastian E., Benjamin, Daniel J., Bergmann, Sven, Boerwinkle, Eric, Bottinger, Erwin P., Campbell, Archie, Chakravarti, Aravinda, Chan, Yingleong, Chanock, Stephen J., Chen, Constance, Chen, Y. D. Ida, Collins, Francis S., Connell, John, Correa, Adolfo, Cupples, L. Adrienne, Smith, George Davey, Davies, Gail, Dörr, Marcu, Ehret, Georg, Ellis, Stephen B., Feenstra, Bjarke, Feitosa, Mary F., Ford, Ian, Fox, Caroline S., Frayling, Timothy M., Friedrich, Nele, Geller, Frank, Scotland, Generation, Gillham Nasenya, Irina, Gottesman, Omri, Graff, Misa, Grodstein, Francine, Gu, Charle, Haley, Chri, Hammond, Christopher J., Harris, Sarah E., Harris, Tamara B., Hastie, Nicholas D., Heard Costa, Nancy L., Heikkilä, Kauko, Hocking, Lynne J., Homuth, Georg, Hottenga, Jouke Jan, Huang, Jinyan, Huffman, Jennifer E., Hysi, Pirro G., Ikram, M. Arfan, Ingelsson, Erik, Joensuu, Anni, Johansson, Åsa, Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kanoni, Stavroula, Kerr, Shona M., Khan, Nazir M., Koellinger, Philipp, Koistinen, Heikki A., Kooner, Manraj K., Kubo, Michiaki, Kuusisto, Johanna, Lahti, Jari, Launer, Lenore J., Lea, Rodney A., Lehne, Benjamin, Lehtimäki, Terho, Liewald, David C. M., Lind, Lar, Loh, Marie, Lokki, Marja Liisa, London, Stephanie J., Loomis, Stephanie J., Loukola, Anu, Lu, Yingchang, Lumley, Thoma, Lundqvist, Annamari, Männistö, Satu, Marques Vidal, Pedro, Masciullo, Corrado, Matchan, Angela, Mathias, Rasika A., Matsuda, Koichi, Meigs, James B., Meisinger, Christa, Meitinger, Thoma, Menni, Cristina, Mentch, Frank D., Mihailov, Evelin, Milani, Lili, Montasser, May E., Montgomery, Grant W., Morrison, Alanna, Myers, Richard H., Nadukuru, Rajiv, Navarro, Pau, Nalis, Mari, Nieminen, Markku S., Nolte, Ilja M., O'Connor, George T., Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmas, Walter R., Pankow, James S., Patarcic, Inga, Pavani, Francesca, Peyser, Patricia A., Pietilainen, Kirsi, Poulter, Neil, Prokopenko, Inga, Ralhan, Sarju, Redmond, Paul, Rich, Stephen S., Rissanen, Harri, Robino, Antonietta, Rose, Lynda M., Rose, Richard, Sala, Cinzia, Salako, Babatunde, Salomaa, Veikko, Sarin, Antti Pekka, Saxena, Richa, Schmidt, Helena, Scott, Laura J., Scott, William R., Sennblad, Bengt, Seshadri, Sudha, Sever, Peter, Shrestha, Smeeta, Smith, Blair H., Smith, Jennifer A., Soranzo, Nicole, Sotoodehnia, Nona, Southam, Lorraine, Stanton, Alice V., Stathopoulou, Maria G., Strauch, Konstantin, Strawbridge, Rona J., Suderman, Matthew J., Tandon, Nikhil, Tang, Sian Tsun, Taylor, Kent D., Tayo, Bamidele O., Töglhofer, Anna Maria, Tomaszewski, Maciej, Tšernikova, Natalia, Tuomilehto, Jaakko, Uitterlinden, Andre G., Vaidya, Dhananjay, Van Hylckama Vlieg, Astrid, Van Setten, Jessica, Vasankari, Tuula, Vedantam, Sailaja, Vlachopoulou, Efthymia, Vozzi, Diego, Vuoksimaa, Eero, Waldenberger, Melanie, Ware, Erin B., Wentworth Shields, William, Whitfield, John B., Wild, Sarah, Willemsen, Gonneke, Yajnik, Chittaranjan S., Yao, Jie, Zaza, Gianluigi, Zhu, Xiaofeng, Salem, Rany M., Melbye, Mad, Bisgaard, Han, Samani, Nilesh J., Cusi, Daniele, Mackey, David A., Cooper, Richard S., Froguel, Philippe, Pasterkamp, Gerard, Grant, Struan F. A., Hakonarson, Hakon, Ferrucci, Luigi, Scott, Robert A., Morris, Andrew D., Palmer, Colin N. A., Dedoussis, George, Deloukas, Pano, Bertram, Lar, Lindenberger, Ulman, Berndt, Sonja I., Lindgren, Cecilia M., Timpson, Nicholas J., Tönjes, Anke, Munroe, Patricia B., Sørensen, Thorkild I. A., Rotimi, Charles N., Arnett, Donna K., Oldehinkel, Albertine J., Kardia, Sharon L. R., Balkau, Beverley, Gambaro, Giovanni, Morris, Andrew P., Eriksson, Johan G., Wright, Margie J., Martin, Nicholas G., Hunt, Steven C., Starr, John M., Deary, Ian J., Griffiths, Lyn R., Tiemeier, Henning, Pirastu, Nicola, Kaprio, Jaakko, Wareham, Nicholas J., Pérusse, Loui, Wilson, James G., Girotto, Giorgia, Caulfield, Mark J., Raitakari, Olli, Boomsma, Dorret I., Gieger, Christian, Van Der Harst, Pim, Hicks, Andrew A., Kraft, Peter, Sinisalo, Juha, Knekt, Paul, Johannesson, Magnu, Magnusson, Patrik K. E., Hamsten, Ander, Schmidt, Reinhold, Borecki, Ingrid B., Vartiainen, Erkki, Becker, Diane M., Bharadwaj, Dwaipayan, Mohlke, Karen L., Boehnke, Michael, Van Duijn, Cornelia M., Sanghera, Dharambir K., Teumer, Alexander, Zeggini, Eleftheria, Metspalu, Andre, Gasparini, Paolo, Ulivi, Sheila, Ober, Carole, Toniolo, Daniela, Rudan, Igor, Porteous, David J., Ciullo, Marina, Spector, Tim D., Hayward, Caroline, Dupuis, Josée, Loos, Ruth J. F., Wright, Alan F., Chandak, Giriraj R., Vollenweider, Peter, Shuldiner, Alan R., Ridker, Paul M., Rotter, Jerome I., Sattar, Naveed, Gyllensten, Ulf, North, Kari E., Pirastu, Mario, Psaty, Bruce M., Weir, David R., Laakso, Markku, Gudnason, Vilmundur, Takahashi, Atsushi, Chambers, John C., Kooner, Jaspal S., Strachan, David P., Campbell, Harry, Hirschhorn, Joel N., Perola, Marku, Polašek, Ozren, Wilson, James F., Imperial College Healthcare NHS Trust- BRC Funding, National Institute for Health Research, BioBank Japan, Project, The BioBank Japan Project, Ehret, Georg Benedikt, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), and Cardiovascular Centre (CVC)
- Subjects
Male ,Netherlands Twin Register (NTR) ,Blood Pressure ,BLOOD-PRESSURE ,INTELLIGENCE ,Runs of Homozygosity ,DISEASE ,Homozygosity ,Cohort Studies ,Cognition ,Forced Expiratory Volume ,GENETIC-VARIANTS ,Inbreeding depression ,Settore MED/14 - NEFROLOGIA ,Inbreeding ,Inbreeding, Evolutionary genetics, Quantitative trait loci ,Non-U.S. Gov't ,Dominance (genetics) ,ddc:616 ,Genetics ,ARCHITECTURE ,Genome ,Multidisciplinary ,Body Height/genetics ,Research Support, Non-U.S. Gov't ,Homozygote ,Confounding ,heterozygosity ,inbreeding ,genomics ,QUANTITATIVE TRAITS ,BioBank Japan Project ,Biological Evolution ,Multidisciplinary Sciences ,Cholesterol ,Phenotype ,Cholesterol, LDL/genetics ,Trait ,Science & Technology - Other Topics ,Educational Status ,Female ,Lung Volume Measurements ,Human ,INBREEDING DEPRESSION ,Quantitative trait loci ,Blood Pressure/genetics ,General Science & Technology ,Forced Expiratory Volume/genetics ,Lung Volume Measurement ,Quantitative trait locus ,Biology ,Research Support ,Evolutionary genetics ,Article ,LDL ,SDG 3 - Good Health and Well-being ,MD Multidisciplinary ,Journal Article ,Humans ,Genetic association ,Science & Technology ,Genome, Human ,ta1184 ,PATHWAYS ,Cholesterol, LDL ,Body Height ,Educational Statu ,ASSOCIATION ANALYSIS ,Evolutionary biology ,Genome, Human/genetics ,ta1181 ,Cohort Studie ,Meta-Analysis - Abstract
Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10-300, 2.1 × 10-6, 2.5 × 10-10 and 1.8 × 10-10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
- Published
- 2015
21. A genome-wide association study of early menopause and the combined impact of identified variants.
- Author
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ReproGen Consortium, Perry, J.R., Corre, T., Esko, T., Chasman, D.I., Fischer, K., Franceschini, N., He, C., Kutalik, Z., Mangino, M., Rose, L.M., Vernon Smith, A., Stolk, L., Sulem, P., Weedon, M.N., Zhuang, W.V., Arnold, A., Ashworth, A., Bergmann, S., Buring, J.E., Burri, A., Chen, C., Cornelis, M.C., Couper, D.J., Goodarzi, M.O., Gudnason, V., Harris, T., Hofman, A., Jones, M., Kraft, P., Launer, L., Laven, J.S., Li, G., McKnight, B., Masciullo, C., Milani, L., Orr, N., Psaty, B.M., Ridker, P.M., Rivadeneira, F., Sala, C., Salumets, A., Schoemaker, M., Traglia, M., Waeber, G., Chanock, S.J., Demerath, E.W., Garcia, M., Hankinson, S.E., Hu, F.B., Hunter, D.J., Lunetta, K.L., Metspalu, A., Montgomery, G.W., Murabito, J.M., Newman, A.B., Ong, K.K., Spector, T.D., Stefansson, K., Swerdlow, A.J., Thorsteinsdottir, U., Van Dam, R.M., Uitterlinden, A.G., Visser, J.A., Vollenweider, P., Toniolo, D., Murray, A., ReproGen Consortium, Perry, J.R., Corre, T., Esko, T., Chasman, D.I., Fischer, K., Franceschini, N., He, C., Kutalik, Z., Mangino, M., Rose, L.M., Vernon Smith, A., Stolk, L., Sulem, P., Weedon, M.N., Zhuang, W.V., Arnold, A., Ashworth, A., Bergmann, S., Buring, J.E., Burri, A., Chen, C., Cornelis, M.C., Couper, D.J., Goodarzi, M.O., Gudnason, V., Harris, T., Hofman, A., Jones, M., Kraft, P., Launer, L., Laven, J.S., Li, G., McKnight, B., Masciullo, C., Milani, L., Orr, N., Psaty, B.M., Ridker, P.M., Rivadeneira, F., Sala, C., Salumets, A., Schoemaker, M., Traglia, M., Waeber, G., Chanock, S.J., Demerath, E.W., Garcia, M., Hankinson, S.E., Hu, F.B., Hunter, D.J., Lunetta, K.L., Metspalu, A., Montgomery, G.W., Murabito, J.M., Newman, A.B., Ong, K.K., Spector, T.D., Stefansson, K., Swerdlow, A.J., Thorsteinsdottir, U., Van Dam, R.M., Uitterlinden, A.G., Visser, J.A., Vollenweider, P., Toniolo, D., and Murray, A.
- Abstract
Early menopause (EM) affects up to 10% of the female population, reducing reproductive lifespan considerably. Currently, it constitutes the leading cause of infertility in the western world, affecting mainly those women who postpone their first pregnancy beyond the age of 30 years. The genetic aetiology of EM is largely unknown in the majority of cases. We have undertaken a meta-analysis of genome-wide association studies (GWASs) in 3493 EM cases and 13 598 controls from 10 independent studies. No novel genetic variants were discovered, but the 17 variants previously associated with normal age at natural menopause as a quantitative trait (QT) were also associated with EM and primary ovarian insufficiency (POI). Thus, EM has a genetic aetiology which overlaps variation in normal age at menopause and is at least partly explained by the additive effects of the same polygenic variants. The combined effect of the common variants captured by the single nucleotide polymorphism arrays was estimated to account for ∼30% of the variance in EM. The association between the combined 17 variants and the risk of EM was greater than the best validated non-genetic risk factor, smoking.
- Published
- 2013
22. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.
- Author
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DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Multiple Tissue Human Expression Resource (MUTHER) Consortium, Ahmadi, K.R., Ainali, C., Barrett, A., Bataille, V., Bell, J.T., Buil, A., Deloukas, P., Dermitzakis, E.T., Dimas, A.S., Durbin, R., Glass, D., Grundberg, E., Hassanali, N., Hedman, Å.K., Ingle, C., Knowles, D., Krestyaninova, M., Lindgren, C.M., Lowe, C.E., McCarthy, M.I., Meduri, E., di Meglio, P., Min, J.L., Montgomery, S.B., Nestle, F.O., Nica, A.C., Nisbet, J., O'Rahilly, S., Parts, L., Potter, S., Sekowska, M., Shin, S.Y., Small, K.S., Soranzo, N., Spector, T.D., Surdulescu, G., Travers, M.E., Tsaprouni, L., Tsoka, S., Wilk, A., Yang, T.P., Zondervan, K.T., Voight, B.F., Scott, L.J., Steinthorsdottir, V., Morris, A.P., Dina, C., Welch, R.P., Zeggini, E., Huth, C., Aulchenko, Y.S., Thorleifsson, G., McCulloch, L.J., Ferreira, T., Grallert, H., Amin, N., Wu, G., Willer, C.J., Raychaudhuri, S., McCarroll, S.A., Langenberg, C., Hofmann, O.M., Dupuis, J., Qi, L., Segrè, A.V., van Hoek, M., Navarro, P., Ardlie, K., Balkau, B., Benediktsson, R., Bennett, A.J., Blagieva, R., Boerwinkle, E., Bonnycastle, L.L., Boström, K.B., Bravenboer, B., Bumpstead, S., Burtt, N.P., Charpentier, G., Chines, P.S., Cornelis, M., Couper, D.J., Crawford, G., Doney, A.S., Elliott, K.S., Elliott, A.L., Erdos, M.R., Fox, C.S., Franklin, C.S., Ganser, M., Gieger, C., Grarup, N., Green, T., Griffin, S., Groves, C.J., Guiducci, C., Hadjadj, S., Herder, C., Isomaa, B., Jackson, A.U., Johnson, P.R., Jørgensen, T., Kao, W.H., Klopp, N., Kong, A., Kraft, P., Kuusisto, J., Lauritzen, T., Li, M., Lieverse, A., Lyssenko, V., Marre, M., Meitinger, T., Midthjell, K., Morken, M.A., Narisu, N., Nilsson, P., Owen, K.R., Payne, F., Perry, J.R., Petersen, A.K., Platou, C., Proença, C., Prokopenko, I., Rathmann, W., Rayner, N.W., Robertson, N.R., Rocheleau, G., Roden, M., Sampson, M.J., Saxena, R., Shields, B.M., Shrader, P., Sigurdsson, G., Sparsø, T., Strassburger, K., Stringham, H.M., Sun, Q., Swift, A.J., Thorand, B., Tichet, J., Tuomi, T., van Dam, R.M., van Haeften, T.W., van Herpt, T., van Vliet-Ostaptchouk, J.V., Walters, G.B., Weedon, M.N., Wijmenga, C., Witteman, J., Bergman, R.N., Cauchi, S., Collins, F.S., Gloyn, A.L., Gyllensten, U., Hansen, T., Hide, W.A., Hitman, G.A., Hofman, A., Hunter, D.J., Hveem, K., Laakso, M., Mohlke, K.L., Morris, A.D., Palmer, C.N., Pramstaller, P.P., Rudan, I., Sijbrands, E., Stein, L.D., Tuomilehto, J., Uitterlinden, A., Walker, M., Wareham, N.J., Watanabe, R.M., Abecasis, G.R., Boehm, B.O., Campbell, H., Daly, M.J., Hattersley, A.T., Hu, F.B., Meigs, J.B., Pankow, J.S., Pedersen, O., Wichmann, H.E., Barroso, I., Florez, J.C., Frayling, T.M., Groop, L., Sladek, R., Thorsteinsdottir, U., Wilson, J.F., Illig, T., Froguel, P., van Duijn, C.M., Stefansson, K., Altshuler, D., Boehnke, M., Manning, A.K., Hivert, M.F., Scott, R.A., Grimsby, J.L., Bouatia-Naji, N., Chen, H., Rybin, D., Liu, C.T., Bielak, L.F., Barnes, D., Cadby, G., Hottenga, J.J., Ingelsson, E., Johnson, T., Kanoni, S., Ladenvall, C., Lagou, V., Lahti, J., Lecoeur, C., Liu, Y., Martinez-Larrad, M.T., Montasser, M.E., Rasmussen-Torvik, L.J., Salo, P., Sattar, N., Shungin, D., Strawbridge, R.J., Tanaka, T., An, P., de Andrade, M., Andrews, J.S., Aspelund, T., Atalay, M., Aulchenko, Y., Bandinelli, S., Beckmann, J.S., Beilby, J.P., Bellis, C., Blangero, J., Boban, M., Boomsma, D.I., Borecki, I.B., Böttcher, Y., Bouchard, C., Brunner, E., Budimir, D., Carlson, O., Clarke, R., Corbatón-Anchuelo, A., Couper, D., de Faire, U., Dedoussis, G.V., Dimitriou, M., Egan, J.M., Eiriksdottir, G., Eriksson, J.G., Eury, E., Ferrucci, L., Ford, I., Forouhi, N.G., Franzosi, M.G., Franks, P.W., Galan, P., de Geus, E., Gigante, B., Glazer, N.L., Goel, A., Gudnason, V., Hallmans, G., Hamsten, A., Hansson, O., Harris, T.B., Hayward, C., Heath, S., Hercberg, S., Hicks, A.A., Hingorani, A., Hui, J., Hung, J., Jarvelin, M.R., Jhun, M.A., Johnson, P.C., Jukema, J.W., Jula, A., Kaprio, J., Kardia, S.L., Keinanen-Kiukaanniemi, S., Kivimaki, M., Kolcic, I., Kovacs, P., Kumari, M., Kyvik, K.O., Lakka, T., Lannfelt, L., Lathrop, G.M., Launer, L.J., Leander, K., Li, G., Lind, L., Lindstrom, J., Lobbens, S., Loos, R.J., Luan, J., Mägi, R., Magnusson, P.K., Marmot, M., Meneton, P., Mooser, V., Miljkovic, I., O'Connell, J., Ong, K.K., Oostra, B.A., Palmer, L.J., Palotie, A., Peden, J.F., Pedersen, N.L., Pehlic, M., Peltonen, L., Penninx, B., Pericic, M., Perola, M., Perusse, L., Peyser, P.A., Polasek, O., Province, M.A., Räikkönen, K., Rauramaa, R., Rehnberg, E., Rice, K., Rotter, J.I., Ruokonen, A., Saaristo, T., Sabater-Lleal, M., Salomaa, V., Savage, D.B., Schwarz, P., Seedorf, U., Sennblad, B., Serrano-Rios, M., Shuldiner, A.R., Sijbrands, E.J., Siscovick, D.S., Smit, J.H., Smith, N.L., Smith, A.V., Stančáková, A., Stirrups, K., Stumvoll, M., Sun, Y.V., Tönjes, A., Trompet, S., Uitterlinden, A.G., Uusitupa, M., Vikström, M., Vitart, V., Vohl, M.C., Vollenweider, P., Waeber, G., Waterworth, D.M., Watkins, H., Wheeler, E., Widen, E., Wild, S.H., Willems, S.M., Willemsen, G., Witteman, J.C., Wright, A.F., Yaghootkar, H., Zelenika, D., Zemunik, T., Zgaga, L., DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Multiple Tissue Human Expression Resource (MUTHER) Consortium, Ahmadi, K.R., Ainali, C., Barrett, A., Bataille, V., Bell, J.T., Buil, A., Deloukas, P., Dermitzakis, E.T., Dimas, A.S., Durbin, R., Glass, D., Grundberg, E., Hassanali, N., Hedman, Å.K., Ingle, C., Knowles, D., Krestyaninova, M., Lindgren, C.M., Lowe, C.E., McCarthy, M.I., Meduri, E., di Meglio, P., Min, J.L., Montgomery, S.B., Nestle, F.O., Nica, A.C., Nisbet, J., O'Rahilly, S., Parts, L., Potter, S., Sekowska, M., Shin, S.Y., Small, K.S., Soranzo, N., Spector, T.D., Surdulescu, G., Travers, M.E., Tsaprouni, L., Tsoka, S., Wilk, A., Yang, T.P., Zondervan, K.T., Voight, B.F., Scott, L.J., Steinthorsdottir, V., Morris, A.P., Dina, C., Welch, R.P., Zeggini, E., Huth, C., Aulchenko, Y.S., Thorleifsson, G., McCulloch, L.J., Ferreira, T., Grallert, H., Amin, N., Wu, G., Willer, C.J., Raychaudhuri, S., McCarroll, S.A., Langenberg, C., Hofmann, O.M., Dupuis, J., Qi, L., Segrè, A.V., van Hoek, M., Navarro, P., Ardlie, K., Balkau, B., Benediktsson, R., Bennett, A.J., Blagieva, R., Boerwinkle, E., Bonnycastle, L.L., Boström, K.B., Bravenboer, B., Bumpstead, S., Burtt, N.P., Charpentier, G., Chines, P.S., Cornelis, M., Couper, D.J., Crawford, G., Doney, A.S., Elliott, K.S., Elliott, A.L., Erdos, M.R., Fox, C.S., Franklin, C.S., Ganser, M., Gieger, C., Grarup, N., Green, T., Griffin, S., Groves, C.J., Guiducci, C., Hadjadj, S., Herder, C., Isomaa, B., Jackson, A.U., Johnson, P.R., Jørgensen, T., Kao, W.H., Klopp, N., Kong, A., Kraft, P., Kuusisto, J., Lauritzen, T., Li, M., Lieverse, A., Lyssenko, V., Marre, M., Meitinger, T., Midthjell, K., Morken, M.A., Narisu, N., Nilsson, P., Owen, K.R., Payne, F., Perry, J.R., Petersen, A.K., Platou, C., Proença, C., Prokopenko, I., Rathmann, W., Rayner, N.W., Robertson, N.R., Rocheleau, G., Roden, M., Sampson, M.J., Saxena, R., Shields, B.M., Shrader, P., Sigurdsson, G., Sparsø, T., Strassburger, K., Stringham, H.M., Sun, Q., Swift, A.J., Thorand, B., Tichet, J., Tuomi, T., van Dam, R.M., van Haeften, T.W., van Herpt, T., van Vliet-Ostaptchouk, J.V., Walters, G.B., Weedon, M.N., Wijmenga, C., Witteman, J., Bergman, R.N., Cauchi, S., Collins, F.S., Gloyn, A.L., Gyllensten, U., Hansen, T., Hide, W.A., Hitman, G.A., Hofman, A., Hunter, D.J., Hveem, K., Laakso, M., Mohlke, K.L., Morris, A.D., Palmer, C.N., Pramstaller, P.P., Rudan, I., Sijbrands, E., Stein, L.D., Tuomilehto, J., Uitterlinden, A., Walker, M., Wareham, N.J., Watanabe, R.M., Abecasis, G.R., Boehm, B.O., Campbell, H., Daly, M.J., Hattersley, A.T., Hu, F.B., Meigs, J.B., Pankow, J.S., Pedersen, O., Wichmann, H.E., Barroso, I., Florez, J.C., Frayling, T.M., Groop, L., Sladek, R., Thorsteinsdottir, U., Wilson, J.F., Illig, T., Froguel, P., van Duijn, C.M., Stefansson, K., Altshuler, D., Boehnke, M., Manning, A.K., Hivert, M.F., Scott, R.A., Grimsby, J.L., Bouatia-Naji, N., Chen, H., Rybin, D., Liu, C.T., Bielak, L.F., Barnes, D., Cadby, G., Hottenga, J.J., Ingelsson, E., Johnson, T., Kanoni, S., Ladenvall, C., Lagou, V., Lahti, J., Lecoeur, C., Liu, Y., Martinez-Larrad, M.T., Montasser, M.E., Rasmussen-Torvik, L.J., Salo, P., Sattar, N., Shungin, D., Strawbridge, R.J., Tanaka, T., An, P., de Andrade, M., Andrews, J.S., Aspelund, T., Atalay, M., Aulchenko, Y., Bandinelli, S., Beckmann, J.S., Beilby, J.P., Bellis, C., Blangero, J., Boban, M., Boomsma, D.I., Borecki, I.B., Böttcher, Y., Bouchard, C., Brunner, E., Budimir, D., Carlson, O., Clarke, R., Corbatón-Anchuelo, A., Couper, D., de Faire, U., Dedoussis, G.V., Dimitriou, M., Egan, J.M., Eiriksdottir, G., Eriksson, J.G., Eury, E., Ferrucci, L., Ford, I., Forouhi, N.G., Franzosi, M.G., Franks, P.W., Galan, P., de Geus, E., Gigante, B., Glazer, N.L., Goel, A., Gudnason, V., Hallmans, G., Hamsten, A., Hansson, O., Harris, T.B., Hayward, C., Heath, S., Hercberg, S., Hicks, A.A., Hingorani, A., Hui, J., Hung, J., Jarvelin, M.R., Jhun, M.A., Johnson, P.C., Jukema, J.W., Jula, A., Kaprio, J., Kardia, S.L., Keinanen-Kiukaanniemi, S., Kivimaki, M., Kolcic, I., Kovacs, P., Kumari, M., Kyvik, K.O., Lakka, T., Lannfelt, L., Lathrop, G.M., Launer, L.J., Leander, K., Li, G., Lind, L., Lindstrom, J., Lobbens, S., Loos, R.J., Luan, J., Mägi, R., Magnusson, P.K., Marmot, M., Meneton, P., Mooser, V., Miljkovic, I., O'Connell, J., Ong, K.K., Oostra, B.A., Palmer, L.J., Palotie, A., Peden, J.F., Pedersen, N.L., Pehlic, M., Peltonen, L., Penninx, B., Pericic, M., Perola, M., Perusse, L., Peyser, P.A., Polasek, O., Province, M.A., Räikkönen, K., Rauramaa, R., Rehnberg, E., Rice, K., Rotter, J.I., Ruokonen, A., Saaristo, T., Sabater-Lleal, M., Salomaa, V., Savage, D.B., Schwarz, P., Seedorf, U., Sennblad, B., Serrano-Rios, M., Shuldiner, A.R., Sijbrands, E.J., Siscovick, D.S., Smit, J.H., Smith, N.L., Smith, A.V., Stančáková, A., Stirrups, K., Stumvoll, M., Sun, Y.V., Tönjes, A., Trompet, S., Uitterlinden, A.G., Uusitupa, M., Vikström, M., Vitart, V., Vohl, M.C., Vollenweider, P., Waeber, G., Waterworth, D.M., Watkins, H., Wheeler, E., Widen, E., Wild, S.H., Willems, S.M., Willemsen, G., Witteman, J.C., Wright, A.F., Yaghootkar, H., Zelenika, D., Zemunik, T., and Zgaga, L.
- Abstract
Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.
- Published
- 2012
23. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.
- Author
-
DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC investigators, GLGC Consortium, Olson, J., Kronmal, R., Robbins, J., Chaves, PH., Burke, G., Kuller, LH., Tracy, R., Gottdiener, J., Prineas, R., Becker, JT., Enright, P., Klein, R., O'Leary, DH., Dastani, Z., Hivert, M.F., Timpson, N., Perry, J.R., Yuan, X., Scott, R.A., Henneman, P., Heid, I.M., Kizer, J.R., Lyytikäinen, L.P., Fuchsberger, C., Tanaka, T., Morris, A.P., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, J.S., Uh, H.W., Wu, Y., Bidulescu, A., Rasmussen-Torvik, L.J., Greenwood, C.M., Ladouceur, M., Grimsby, J., Manning, A.K., Liu, C.T., Kooner, J., Mooser, V.E., Vollenweider, P., Kapur, K.A., Chambers, J., Wareham, N.J., Langenberg, C., Frants, R., Willems-Vandijk, K., Oostra, B.A., Willems, S.M., Lamina, C., Winkler, T.W., Psaty, B.M., Tracy, R.P., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, P.P., Evans, D.M., St Pourcain, B., Sattar, N., Wood, A.R., Bandinelli, S., Carlson, O.D., Egan, J.M., Böhringer, S., van Heemst, D., Kedenko, L., Kristiansson, K., Nuotio, M.L., Loo, B.M., Harris, T., Garcia, M., Kanaya, A., Haun, M., Klopp, N., Wichmann, H.E., Deloukas, P., Katsareli, E., Couper, D.J., Duncan, B.B., Kloppenburg, M., Adair, L.S., Borja, J.B., Wilson, J.G., Musani, S., Guo, X., Johnson, T., Semple, R., Teslovich, T.M., Allison, M.A., Redline, S., Buxbaum, S.G., Mohlke, K.L., Meulenbelt, I., Ballantyne, C.M., Dedoussis, G.V., Hu, F.B., Liu, Y., Paulweber, B., Spector, T.D., Slagboom, P.E., Ferrucci, L., Jula, A., Perola, M., Raitakari, O., Florez, J.C., Salomaa, V., Eriksson, J.G., Frayling, T.M., Hicks, A.A., Lehtimäki, T., Smith, G.D., Siscovick, D.S., Kronenberg, F., van Duijn, C., Loos, R.J., Waterworth, D.M., Meigs, J.B., Dupuis, J., Richards, J.B., Voight, B.F., Scott, L.J., Steinthorsdottir, V., Dina, C., Welch, R.P., Zeggini, E., Huth, C., Aulchenko, Y.S., Thorleifsson, G., McCulloch, L.J., Ferreira, T., Grallert, H., Amin, N., Wu, G., Willer, C.J., Raychaudhuri, S., McCarroll, S.A., Hofmann, O.M., Segrè, A.V., van Hoek, M., Navarro, P., Ardlie, K., Balkau, B., Benediktsson, R., Bennett, A.J., Blagieva, R., Boerwinkle, E., Bonnycastle, L.L., Boström, K.B., Bravenboer, B., Bumpstead, S., Burtt, N.P., Charpentier, G., Chines, P.S., Cornelis, M., Crawford, G., Doney, A.S., Elliott, K.S., Elliott, A.L., Erdos, M.R., Fox, C.S., Franklin, C.S., Ganser, M., Gieger, C., Grarup, N., Green, T., Griffin, S., Groves, C.J., Guiducci, C., Hadjadj, S., Hassanali, N., Herder, C., Isomaa, B., Jackson, A.U., Johnson, P.R., Jørgensen, T., Kao, W.H., Kong, A., Kraft, P., Kuusisto, J., Lauritzen, T., Li, M., Lieverse, A., Lindgren, C.M., Lyssenko, V., Marre, M., Meitinger, T., Midthjell, K., Morken, M.A., Narisu, N., Nilsson, P., Owen, K.R., Payne, F., Petersen, A.K., Platou, C., Proença, C., Prokopenko, I., Rathmann, W., Rayner, N.W., Robertson, N.R., Rocheleau, G., Roden, M., Sampson, M.J., Saxena, R., Shields, B.M., Shrader, P., Sigurdsson, G., Sparsø, T., Strassburger, K., Stringham, H.M., Sun, Q., Swift, A.J., Thorand, B., Tichet, J., Tuomi, T., van Dam, R.M., van Haeften, T.W., van Herpt, T., van Vliet-Ostaptchouk, J.V., Walters, G.B., Weedon, M.N., Wijmenga, C., Witteman, J., Bergman, R.N., Cauchi, S., Collins, F.S., Gloyn, A.L., Gyllensten, U., Hansen, T., Hide, W.A., Hitman, G.A., Hofman, A., Hunter, D.J., Hveem, K., Laakso, M., Morris, A.D., Palmer, C.N., Rudan, I., Sijbrands, E., Stein, L.D., Tuomilehto, J., Uitterlinden, A., Walker, M., Watanabe, R.M., Abecasis, G.R., Boehm, B.O., Campbell, H., Daly, M.J., Hattersley, A.T., Pedersen, O., Barroso, I., Groop, L., Sladek, R., Thorsteinsdottir, U., Wilson, J.F., Illig, T., Froguel, P., van Duijn, C.M., Stefansson, K., Altshuler, D., Boehnke, M., McCarthy, M.I., Soranzo, N., Wheeler, E., Glazer, N.L., Bouatia-Naji, N., Mägi, R., Randall, J., Elliott, P., Rybin, D., Dehghan, A., Hottenga, J.J., Song, K., Goel, A., Lajunen, T., Doney, A., Cavalcanti-Proença, C., Kumari, M., Timpson, N.J., Zabena, C., Ingelsson, E., An, P., O'Connell, J., Luan, J., Elliott, A., Roccasecca, R.M., Pattou, F., Sethupathy, P., Ariyurek, Y., Barter, P., Beilby, J.P., Ben-Shlomo, Y., Bergmann, S., Bochud, M., Bonnefond, A., Borch-Johnsen, K., Böttcher, Y., Brunner, E., Bumpstead, S.J., Chen, Y.D., Chines, P., Clarke, R., Coin, L.J., Cooper, M.N., Crisponi, L., Day, I.N., de Geus, E.J., Delplanque, J., Fedson, A.C., Fischer-Rosinsky, A., Forouhi, N.G., Franzosi, M.G., Galan, P., Goodarzi, M.O., Graessler, J., Grundy, S., Gwilliam, R., Hallmans, G., Hammond, N., Han, X., Hartikainen, A.L., Hayward, C., Heath, S.C., Hercberg, S., Hillman, D.R., Hingorani, A.D., Hui, J., Hung, J., Kaakinen, M., Kaprio, J., Kesaniemi, Y.A., Kivimaki, M., Knight, B., Koskinen, S., Kovacs, P., Kyvik, K.O., Lathrop, G.M., Lawlor, D.A., Le Bacquer, O., Lecoeur, C., Li, Y., Mahley, R., Mangino, M., Martínez-Larrad, M.T., McAteer, J.B., McPherson, R., Meisinger, C., Melzer, D., Meyre, D., Mitchell, B.D., Mukherjee, S., Naitza, S., Neville, M.J., Orrù, M., Pakyz, R., Paolisso, G., Pattaro, C., Pearson, D., Peden, J.F., Pedersen, N.L., Pfeiffer, A.F., Pichler, I., Polasek, O., Posthuma, D., Potter, S.C., Pouta, A., Province, M.A., Rice, K., Ripatti, S., Rivadeneira, F., Rolandsson, O., Sandbaek, A., Sandhu, M., Sanna, S., Sayer, A.A., Scheet, P., Seedorf, U., Sharp, S.J., Shields, B., Sigurðsson, G., Sijbrands, E.J., Silveira, A., Simpson, L., Singleton, A., Smith, N.L., Sovio, U., Swift, A., Syddall, H., Syvänen, A.C., Tönjes, A., Uitterlinden, A.G., van Dijk, K.W., Varma, D., Visvikis-Siest, S., Vitart, V., Vogelzangs, N., Waeber, G., Wagner, P.J., Walley, A., Ward, K.L., Watkins, H., Wild, S.H., Willemsen, G., Witteman, J.C., Yarnell, J.W., Zelenika, D., Zethelius, B., Zhai, G., Zhao, J.H., Zillikens, M.C., Borecki, I.B., Meneton, P., Magnusson, P.K., Nathan, D.M., Williams, G.H., Silander, K., Bornstein, S.R., Schwarz, P., Spranger, J., Karpe, F., Shuldiner, A.R., Cooper, C., Serrano-Ríos, M., Lind, L., Palmer, L.J., Franks, P.W., Ebrahim, S., Marmot, M., Wright, A.F., Stumvoll, M., Hamsten, A., Buchanan, T.A., Valle, T.T., Rotter, J.I., Penninx, B.W., Boomsma, D.I., Cao, A., Scuteri, A., Schlessinger, D., Uda, M., Ruokonen, A., Jarvelin, M.R., Peltonen, L., Mooser, V., Musunuru, K., Smith, A.V., Edmondson, A.C., Stylianou, I.M., Koseki, M., Pirruccello, J.P., Chasman, D.I., Johansen, C.T., Fouchier, S.W., Peloso, G.M., Barbalic, M., Ricketts, S.L., Bis, J.C., Feitosa, M.F., Orho-Melander, M., Melander, O., Li, X., Cho, Y.S., Go, M.J., Kim, Y.J., Lee, J.Y., Park, T., Kim, K., Sim, X., Ong, R.T., Croteau-Chonka, D.C., Lange, L.A., Smith, J.D., Ziegler, A., Zhang, W., Zee, R.Y., Whitfield, J.B., Thompson, J.R., Surakka, I., Smit, J.H., Sinisalo, J., Scott, J., Saharinen, J., Sabatti, C., Rose, L.M., Roberts, R., Rieder, M., Parker, A.N., Pare, G., O'Donnell, C.J., Nieminen, M.S., Nickerson, D.A., Montgomery, G.W., McArdle, W., Masson, D., Martin, N.G., Marroni, F., Lucas, G., Luben, R., Lokki, M.L., Lettre, G., Launer, L.J., Lakatta, E.G., Laaksonen, R., König, I.R., Khaw, K.T., Kaplan, L.M., Johansson, Å., Janssens, A.C., Igl, W., Hovingh, G.K., Hengstenberg, C., Havulinna, A.S., Hastie, N.D., Harris, T.B., Haritunians, T., Hall, A.S., Groop, L.C., Gonzalez, E., Freimer, N.B., Erdmann, J., Ejebe, K.G., Döring, A., Dominiczak, A.F., Demissie, S., de Faire, U., Caulfield, M.J., Boekholdt, S.M., Assimes, T.L., Quertermous, T., Seielstad, M., Wong, T.Y., Tai, E.S., Feranil, A.B., Kuzawa, C.W., Taylor, H.A., Gabriel, S.B., Holm, H., Gudnason, V., Krauss, R.M., Ordovas, J.M., Munroe, P.B., Kooner, J.S., Tall, A.R., Hegele, R.A., Kastelein, J.J., Schadt, E.E., Strachan, D.P., Reilly, M.P., Samani, N.J., Schunkert, H., Cupples, L.A., Sandhu, M.S., Ridker, P.M., Rader, D.J., Kathiresan, S., DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC investigators, GLGC Consortium, Olson, J., Kronmal, R., Robbins, J., Chaves, PH., Burke, G., Kuller, LH., Tracy, R., Gottdiener, J., Prineas, R., Becker, JT., Enright, P., Klein, R., O'Leary, DH., Dastani, Z., Hivert, M.F., Timpson, N., Perry, J.R., Yuan, X., Scott, R.A., Henneman, P., Heid, I.M., Kizer, J.R., Lyytikäinen, L.P., Fuchsberger, C., Tanaka, T., Morris, A.P., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, J.S., Uh, H.W., Wu, Y., Bidulescu, A., Rasmussen-Torvik, L.J., Greenwood, C.M., Ladouceur, M., Grimsby, J., Manning, A.K., Liu, C.T., Kooner, J., Mooser, V.E., Vollenweider, P., Kapur, K.A., Chambers, J., Wareham, N.J., Langenberg, C., Frants, R., Willems-Vandijk, K., Oostra, B.A., Willems, S.M., Lamina, C., Winkler, T.W., Psaty, B.M., Tracy, R.P., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, P.P., Evans, D.M., St Pourcain, B., Sattar, N., Wood, A.R., Bandinelli, S., Carlson, O.D., Egan, J.M., Böhringer, S., van Heemst, D., Kedenko, L., Kristiansson, K., Nuotio, M.L., Loo, B.M., Harris, T., Garcia, M., Kanaya, A., Haun, M., Klopp, N., Wichmann, H.E., Deloukas, P., Katsareli, E., Couper, D.J., Duncan, B.B., Kloppenburg, M., Adair, L.S., Borja, J.B., Wilson, J.G., Musani, S., Guo, X., Johnson, T., Semple, R., Teslovich, T.M., Allison, M.A., Redline, S., Buxbaum, S.G., Mohlke, K.L., Meulenbelt, I., Ballantyne, C.M., Dedoussis, G.V., Hu, F.B., Liu, Y., Paulweber, B., Spector, T.D., Slagboom, P.E., Ferrucci, L., Jula, A., Perola, M., Raitakari, O., Florez, J.C., Salomaa, V., Eriksson, J.G., Frayling, T.M., Hicks, A.A., Lehtimäki, T., Smith, G.D., Siscovick, D.S., Kronenberg, F., van Duijn, C., Loos, R.J., Waterworth, D.M., Meigs, J.B., Dupuis, J., Richards, J.B., Voight, B.F., Scott, L.J., Steinthorsdottir, V., Dina, C., Welch, R.P., Zeggini, E., Huth, C., Aulchenko, Y.S., Thorleifsson, G., McCulloch, L.J., Ferreira, T., Grallert, H., Amin, N., Wu, G., Willer, C.J., Raychaudhuri, S., McCarroll, S.A., Hofmann, O.M., Segrè, A.V., van Hoek, M., Navarro, P., Ardlie, K., Balkau, B., Benediktsson, R., Bennett, A.J., Blagieva, R., Boerwinkle, E., Bonnycastle, L.L., Boström, K.B., Bravenboer, B., Bumpstead, S., Burtt, N.P., Charpentier, G., Chines, P.S., Cornelis, M., Crawford, G., Doney, A.S., Elliott, K.S., Elliott, A.L., Erdos, M.R., Fox, C.S., Franklin, C.S., Ganser, M., Gieger, C., Grarup, N., Green, T., Griffin, S., Groves, C.J., Guiducci, C., Hadjadj, S., Hassanali, N., Herder, C., Isomaa, B., Jackson, A.U., Johnson, P.R., Jørgensen, T., Kao, W.H., Kong, A., Kraft, P., Kuusisto, J., Lauritzen, T., Li, M., Lieverse, A., Lindgren, C.M., Lyssenko, V., Marre, M., Meitinger, T., Midthjell, K., Morken, M.A., Narisu, N., Nilsson, P., Owen, K.R., Payne, F., Petersen, A.K., Platou, C., Proença, C., Prokopenko, I., Rathmann, W., Rayner, N.W., Robertson, N.R., Rocheleau, G., Roden, M., Sampson, M.J., Saxena, R., Shields, B.M., Shrader, P., Sigurdsson, G., Sparsø, T., Strassburger, K., Stringham, H.M., Sun, Q., Swift, A.J., Thorand, B., Tichet, J., Tuomi, T., van Dam, R.M., van Haeften, T.W., van Herpt, T., van Vliet-Ostaptchouk, J.V., Walters, G.B., Weedon, M.N., Wijmenga, C., Witteman, J., Bergman, R.N., Cauchi, S., Collins, F.S., Gloyn, A.L., Gyllensten, U., Hansen, T., Hide, W.A., Hitman, G.A., Hofman, A., Hunter, D.J., Hveem, K., Laakso, M., Morris, A.D., Palmer, C.N., Rudan, I., Sijbrands, E., Stein, L.D., Tuomilehto, J., Uitterlinden, A., Walker, M., Watanabe, R.M., Abecasis, G.R., Boehm, B.O., Campbell, H., Daly, M.J., Hattersley, A.T., Pedersen, O., Barroso, I., Groop, L., Sladek, R., Thorsteinsdottir, U., Wilson, J.F., Illig, T., Froguel, P., van Duijn, C.M., Stefansson, K., Altshuler, D., Boehnke, M., McCarthy, M.I., Soranzo, N., Wheeler, E., Glazer, N.L., Bouatia-Naji, N., Mägi, R., Randall, J., Elliott, P., Rybin, D., Dehghan, A., Hottenga, J.J., Song, K., Goel, A., Lajunen, T., Doney, A., Cavalcanti-Proença, C., Kumari, M., Timpson, N.J., Zabena, C., Ingelsson, E., An, P., O'Connell, J., Luan, J., Elliott, A., Roccasecca, R.M., Pattou, F., Sethupathy, P., Ariyurek, Y., Barter, P., Beilby, J.P., Ben-Shlomo, Y., Bergmann, S., Bochud, M., Bonnefond, A., Borch-Johnsen, K., Böttcher, Y., Brunner, E., Bumpstead, S.J., Chen, Y.D., Chines, P., Clarke, R., Coin, L.J., Cooper, M.N., Crisponi, L., Day, I.N., de Geus, E.J., Delplanque, J., Fedson, A.C., Fischer-Rosinsky, A., Forouhi, N.G., Franzosi, M.G., Galan, P., Goodarzi, M.O., Graessler, J., Grundy, S., Gwilliam, R., Hallmans, G., Hammond, N., Han, X., Hartikainen, A.L., Hayward, C., Heath, S.C., Hercberg, S., Hillman, D.R., Hingorani, A.D., Hui, J., Hung, J., Kaakinen, M., Kaprio, J., Kesaniemi, Y.A., Kivimaki, M., Knight, B., Koskinen, S., Kovacs, P., Kyvik, K.O., Lathrop, G.M., Lawlor, D.A., Le Bacquer, O., Lecoeur, C., Li, Y., Mahley, R., Mangino, M., Martínez-Larrad, M.T., McAteer, J.B., McPherson, R., Meisinger, C., Melzer, D., Meyre, D., Mitchell, B.D., Mukherjee, S., Naitza, S., Neville, M.J., Orrù, M., Pakyz, R., Paolisso, G., Pattaro, C., Pearson, D., Peden, J.F., Pedersen, N.L., Pfeiffer, A.F., Pichler, I., Polasek, O., Posthuma, D., Potter, S.C., Pouta, A., Province, M.A., Rice, K., Ripatti, S., Rivadeneira, F., Rolandsson, O., Sandbaek, A., Sandhu, M., Sanna, S., Sayer, A.A., Scheet, P., Seedorf, U., Sharp, S.J., Shields, B., Sigurðsson, G., Sijbrands, E.J., Silveira, A., Simpson, L., Singleton, A., Smith, N.L., Sovio, U., Swift, A., Syddall, H., Syvänen, A.C., Tönjes, A., Uitterlinden, A.G., van Dijk, K.W., Varma, D., Visvikis-Siest, S., Vitart, V., Vogelzangs, N., Waeber, G., Wagner, P.J., Walley, A., Ward, K.L., Watkins, H., Wild, S.H., Willemsen, G., Witteman, J.C., Yarnell, J.W., Zelenika, D., Zethelius, B., Zhai, G., Zhao, J.H., Zillikens, M.C., Borecki, I.B., Meneton, P., Magnusson, P.K., Nathan, D.M., Williams, G.H., Silander, K., Bornstein, S.R., Schwarz, P., Spranger, J., Karpe, F., Shuldiner, A.R., Cooper, C., Serrano-Ríos, M., Lind, L., Palmer, L.J., Franks, P.W., Ebrahim, S., Marmot, M., Wright, A.F., Stumvoll, M., Hamsten, A., Buchanan, T.A., Valle, T.T., Rotter, J.I., Penninx, B.W., Boomsma, D.I., Cao, A., Scuteri, A., Schlessinger, D., Uda, M., Ruokonen, A., Jarvelin, M.R., Peltonen, L., Mooser, V., Musunuru, K., Smith, A.V., Edmondson, A.C., Stylianou, I.M., Koseki, M., Pirruccello, J.P., Chasman, D.I., Johansen, C.T., Fouchier, S.W., Peloso, G.M., Barbalic, M., Ricketts, S.L., Bis, J.C., Feitosa, M.F., Orho-Melander, M., Melander, O., Li, X., Cho, Y.S., Go, M.J., Kim, Y.J., Lee, J.Y., Park, T., Kim, K., Sim, X., Ong, R.T., Croteau-Chonka, D.C., Lange, L.A., Smith, J.D., Ziegler, A., Zhang, W., Zee, R.Y., Whitfield, J.B., Thompson, J.R., Surakka, I., Smit, J.H., Sinisalo, J., Scott, J., Saharinen, J., Sabatti, C., Rose, L.M., Roberts, R., Rieder, M., Parker, A.N., Pare, G., O'Donnell, C.J., Nieminen, M.S., Nickerson, D.A., Montgomery, G.W., McArdle, W., Masson, D., Martin, N.G., Marroni, F., Lucas, G., Luben, R., Lokki, M.L., Lettre, G., Launer, L.J., Lakatta, E.G., Laaksonen, R., König, I.R., Khaw, K.T., Kaplan, L.M., Johansson, Å., Janssens, A.C., Igl, W., Hovingh, G.K., Hengstenberg, C., Havulinna, A.S., Hastie, N.D., Harris, T.B., Haritunians, T., Hall, A.S., Groop, L.C., Gonzalez, E., Freimer, N.B., Erdmann, J., Ejebe, K.G., Döring, A., Dominiczak, A.F., Demissie, S., de Faire, U., Caulfield, M.J., Boekholdt, S.M., Assimes, T.L., Quertermous, T., Seielstad, M., Wong, T.Y., Tai, E.S., Feranil, A.B., Kuzawa, C.W., Taylor, H.A., Gabriel, S.B., Holm, H., Gudnason, V., Krauss, R.M., Ordovas, J.M., Munroe, P.B., Kooner, J.S., Tall, A.R., Hegele, R.A., Kastelein, J.J., Schadt, E.E., Strachan, D.P., Reilly, M.P., Samani, N.J., Schunkert, H., Cupples, L.A., Sandhu, M.S., Ridker, P.M., Rader, D.J., and Kathiresan, S.
- Abstract
Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
- Published
- 2012
24. Genome-wide meta-analysis of common variant differences between men and women.
- Author
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Wellcome Trust Case Control Consortium, Boraska, V., Jerončić, A., Colonna, V., Southam, L., Nyholt, D.R., Rayner, N.W., Perry, J.R., Toniolo, D., Albrecht, E., Ang, W., Bandinelli, S., Barbalic, M., Barroso, I., Beckmann, J.S., Biffar, R., Boomsma, D., Campbell, H., Corre, T., Erdmann, J., Esko, T., Fischer, K., Franceschini, N., Frayling, T.M., Girotto, G., Gonzalez, J.R., Harris, T.B., Heath, A.C., Heid, I.M., Hoffmann, W., Hofman, A., Horikoshi, M., Zhao, J.H., Jackson, A.U., Hottenga, J.J., Jula, A., Kähönen, M., Khaw, K.T., Kiemeney, L.A., Klopp, N., Kutalik, Z., Lagou, V., Launer, L.J., Lehtimäki, T., Lemire, M., Lokki, M.L., Loley, C., Luan, J., Mangino, M., Mateo Leach, I., Medland, S.E., Mihailov, E., Montgomery, G.W., Navis, G., Newnham, J., Nieminen, M.S., Palotie, A., Panoutsopoulou, K., Peters, A., Pirastu, N., Polasek, O., Rehnström, K., Ripatti, S., Ritchie, G.R., Rivadeneira, F., Robino, A., Samani, N.J., Shin, S.Y., Sinisalo, J., Smit, J.H., Soranzo, N., Stolk, L., Swinkels, D.W., Tanaka, T., Teumer, A., Tönjes, A., Traglia, M., Tuomilehto, J., Valsesia, A., van Gilst, W.H., van Meurs, J.B., Smith, A.V., Viikari, J., Vink, J.M., Waeber, G., Warrington, N.M., Widen, E., Willemsen, G., Wright, A.F., Zanke, B.W., Zgaga, L., Boehnke, M., d'Adamo, A.P., de Geus, E., Demerath, E.W., den Heijer, M., Eriksson, J.G., Ferrucci, L., Gieger, C., Gudnason, V., Hayward, C., Hengstenberg, C., Hudson, T.J., Järvelin, M.R., Kogevinas, M., Loos, R.J., Martin, N.G., Metspalu, A., Pennell, C.E., Penninx, B.W., Perola, M., Raitakari, O., Salomaa, V., Schreiber, S., Schunkert, H., Spector, T.D., Stumvoll, M., Uitterlinden, A.G., Ulivi, S., van der Harst, P., Vollenweider, P., Völzke, H., Wareham, N.J., Wichmann, H.E., Wilson, J.F., Rudan, I., Xue, Y., Zeggini, E., Wellcome Trust Case Control Consortium, Boraska, V., Jerončić, A., Colonna, V., Southam, L., Nyholt, D.R., Rayner, N.W., Perry, J.R., Toniolo, D., Albrecht, E., Ang, W., Bandinelli, S., Barbalic, M., Barroso, I., Beckmann, J.S., Biffar, R., Boomsma, D., Campbell, H., Corre, T., Erdmann, J., Esko, T., Fischer, K., Franceschini, N., Frayling, T.M., Girotto, G., Gonzalez, J.R., Harris, T.B., Heath, A.C., Heid, I.M., Hoffmann, W., Hofman, A., Horikoshi, M., Zhao, J.H., Jackson, A.U., Hottenga, J.J., Jula, A., Kähönen, M., Khaw, K.T., Kiemeney, L.A., Klopp, N., Kutalik, Z., Lagou, V., Launer, L.J., Lehtimäki, T., Lemire, M., Lokki, M.L., Loley, C., Luan, J., Mangino, M., Mateo Leach, I., Medland, S.E., Mihailov, E., Montgomery, G.W., Navis, G., Newnham, J., Nieminen, M.S., Palotie, A., Panoutsopoulou, K., Peters, A., Pirastu, N., Polasek, O., Rehnström, K., Ripatti, S., Ritchie, G.R., Rivadeneira, F., Robino, A., Samani, N.J., Shin, S.Y., Sinisalo, J., Smit, J.H., Soranzo, N., Stolk, L., Swinkels, D.W., Tanaka, T., Teumer, A., Tönjes, A., Traglia, M., Tuomilehto, J., Valsesia, A., van Gilst, W.H., van Meurs, J.B., Smith, A.V., Viikari, J., Vink, J.M., Waeber, G., Warrington, N.M., Widen, E., Willemsen, G., Wright, A.F., Zanke, B.W., Zgaga, L., Boehnke, M., d'Adamo, A.P., de Geus, E., Demerath, E.W., den Heijer, M., Eriksson, J.G., Ferrucci, L., Gieger, C., Gudnason, V., Hayward, C., Hengstenberg, C., Hudson, T.J., Järvelin, M.R., Kogevinas, M., Loos, R.J., Martin, N.G., Metspalu, A., Pennell, C.E., Penninx, B.W., Perola, M., Raitakari, O., Salomaa, V., Schreiber, S., Schunkert, H., Spector, T.D., Stumvoll, M., Uitterlinden, A.G., Ulivi, S., van der Harst, P., Vollenweider, P., Völzke, H., Wareham, N.J., Wichmann, H.E., Wilson, J.F., Rudan, I., Xue, Y., and Zeggini, E.
- Abstract
The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency >0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P < 5 × 10(-8)) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across ~115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased traits.
- Published
- 2012
25. Genome-wide meta-analysis of common variant differences between men and women
- Author
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Boraska, V., Jeroncic, A., Colonna, V., Southam, L., Nyholt, D.R., William Rayner, N., Perry, J.R., Toniolo, D., Albrecht, E., Ang, W., Bandinelli, S., Barbalic, M., Barroso, I., Beckmann, J.S., Biffar, R., Boomsma, D.I., Campbell, H., Corre, T., Erdmann, J., Esko, T., Fischer, K., Franceschini, N., Frayling, T.M., Girotto, G., Gonzalez, J.R., Harris, T.B., Heath, A.C., Heid, I.M., Hoffmann, W., Hofman, A., Horikoshi, M., Hua Zhao, J., Jackson, A.U., Hottenga, J.J., Jula, A., Kahonen, M., Khaw, K.T., Kiemeney, L.A.L.M., Klopp, N., Kutalik, Z., Lagou, V., Launer, L.J., Lehtimaki, T., Lemire, M., Lokki, M.L., Loley, C., Luan, J., Mangino, M., Mateo Leach, I., Medland, S.E., Mihailov, E., Montgomery, G.W., Navis, G., Newnham, J., Nieminen, M.S., Palotie, A., Panoutsopoulou, K., Peters, A., Pirastu, N., Polasek, O., Rehnstrom, K., Ripatti, S., Ritchie, G.R., Rivadeneira, F., Robino, A., Samani, N.J., Shin, S.Y., Sinisalo, J., Smit, J.H., Soranzo, N., Stolk, L., Swinkels, D.W., Tanaka, T., Teumer, A., Tonjes, A., Traglia, M., Tuomilehto, J., Valsesia, A., van Gilst, W.H., van Meurs, J.B., Smith, A.V., Viikari, J., Vink, J.M., Waeber, G., Warrington, N.M., Widen, E., Willemsen, G., Wright, A.F., Zanke, B.W., Zgaga, L., Wellcome Trust Case Control, C., Boehnke, M., d'Adamo, A.P., de Geus, E., Demerath, E.W., den Heijer, M., Eriksson, J.G., Ferrucci, L., Gieger, C., Gudnason, V., et al., Boraska, V., Jeroncic, A., Colonna, V., Southam, L., Nyholt, D.R., William Rayner, N., Perry, J.R., Toniolo, D., Albrecht, E., Ang, W., Bandinelli, S., Barbalic, M., Barroso, I., Beckmann, J.S., Biffar, R., Boomsma, D.I., Campbell, H., Corre, T., Erdmann, J., Esko, T., Fischer, K., Franceschini, N., Frayling, T.M., Girotto, G., Gonzalez, J.R., Harris, T.B., Heath, A.C., Heid, I.M., Hoffmann, W., Hofman, A., Horikoshi, M., Hua Zhao, J., Jackson, A.U., Hottenga, J.J., Jula, A., Kahonen, M., Khaw, K.T., Kiemeney, L.A.L.M., Klopp, N., Kutalik, Z., Lagou, V., Launer, L.J., Lehtimaki, T., Lemire, M., Lokki, M.L., Loley, C., Luan, J., Mangino, M., Mateo Leach, I., Medland, S.E., Mihailov, E., Montgomery, G.W., Navis, G., Newnham, J., Nieminen, M.S., Palotie, A., Panoutsopoulou, K., Peters, A., Pirastu, N., Polasek, O., Rehnstrom, K., Ripatti, S., Ritchie, G.R., Rivadeneira, F., Robino, A., Samani, N.J., Shin, S.Y., Sinisalo, J., Smit, J.H., Soranzo, N., Stolk, L., Swinkels, D.W., Tanaka, T., Teumer, A., Tonjes, A., Traglia, M., Tuomilehto, J., Valsesia, A., van Gilst, W.H., van Meurs, J.B., Smith, A.V., Viikari, J., Vink, J.M., Waeber, G., Warrington, N.M., Widen, E., Willemsen, G., Wright, A.F., Zanke, B.W., Zgaga, L., Wellcome Trust Case Control, C., Boehnke, M., d'Adamo, A.P., de Geus, E., Demerath, E.W., den Heijer, M., Eriksson, J.G., Ferrucci, L., Gieger, C., and Gudnason, V., et al.
- Abstract
Item does not contain fulltext, The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency >0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P < 5 x 10(-8)) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across approximately 115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased traits.
- Published
- 2012
26. 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
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Dastani, Z., Hivert, M.F., Timpson, N.J., Perry, J.R., Yuan, X., Scott, R.A., Henneman, P., Heid, I.M., Kizer, J.R., Lyytikäinen, L.P., Fuchsberger, C., Tanaka, T., Morris, A.P., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, J.S., Uh, H.W., Wu, Y., Bidulescu, A., Rasmussen-Torvik, L.J., Greenwood, C.M., Ladouceur, M., Grimsby, J., Manning, A.K., Liu, C.T., Kooner, J., Mooser, V.E., Vollenweider, P., Kapur, K.A., Chambers, J., Wareham, N.J., Langenberg, C., Frants, R., Willems van Dijk, K., Oostra, B.A., Willems, S.M., Lamina, C., Winkler, T.W., Psaty, B.M., Tracy, R.P., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, P.P., Evans, D.M., St Pourcain, B., Sattar, N., Wood, A.R., Bandinelli, S., Carlson, O.D., Egan, J.M., Böhringer, S., van Heemst, D., Kedenko, L., Kristiansson, K., Nuotio, M.L., Loo, B.M., Harris, T., Garcia, M., Kanaya, A., Haun, M., Klopp, N., Wichmann, H.E., Deloukas, P., Katsareli, E., Couper, D.J., Duncan, B.B., Kloppenburg, M., Adair, L.S., Borja, J.B., Hottenga, J.J., de Geus, E.J.C., Willemsen, G., Boomsma, D.I., Wilson, J.G., Musani, G., Guo, X., Johnson, T., Semple, R., Teslovich, T.M., Allison, M.A., Redline, S., Buxbaum, S.G., Mohlke, K.L., Meulenbelt, I., Ballantyne, C.M., Dedoussis, G.V., Hu, F.B., Liu, Y., Paulweber, B., Spector, T.D., Slagboom, P.E., Ferrucci, L., Jula, A., Perola, M., Raitakari, O., Florez, J.C., Salomaa, V., Eriksson, J.G., Frayling, T.M., Hicks, A.A., Lehtimäki, T., Smith, G.D., Siscovick, D.S., Kronenberg, F., van Duijn, C.M., Loos, R.J., Waterworth, D., Meigs, J.B., Dupuis, J., Richards, J.B., Posthuma, D., Penninx, B.W.J.H., Vogelzangs, N., Kathiresan, S., Dastani, Z., Hivert, M.F., Timpson, N.J., Perry, J.R., Yuan, X., Scott, R.A., Henneman, P., Heid, I.M., Kizer, J.R., Lyytikäinen, L.P., Fuchsberger, C., Tanaka, T., Morris, A.P., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, J.S., Uh, H.W., Wu, Y., Bidulescu, A., Rasmussen-Torvik, L.J., Greenwood, C.M., Ladouceur, M., Grimsby, J., Manning, A.K., Liu, C.T., Kooner, J., Mooser, V.E., Vollenweider, P., Kapur, K.A., Chambers, J., Wareham, N.J., Langenberg, C., Frants, R., Willems van Dijk, K., Oostra, B.A., Willems, S.M., Lamina, C., Winkler, T.W., Psaty, B.M., Tracy, R.P., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, P.P., Evans, D.M., St Pourcain, B., Sattar, N., Wood, A.R., Bandinelli, S., Carlson, O.D., Egan, J.M., Böhringer, S., van Heemst, D., Kedenko, L., Kristiansson, K., Nuotio, M.L., Loo, B.M., Harris, T., Garcia, M., Kanaya, A., Haun, M., Klopp, N., Wichmann, H.E., Deloukas, P., Katsareli, E., Couper, D.J., Duncan, B.B., Kloppenburg, M., Adair, L.S., Borja, J.B., Hottenga, J.J., de Geus, E.J.C., Willemsen, G., Boomsma, D.I., Wilson, J.G., Musani, G., Guo, X., Johnson, T., Semple, R., Teslovich, T.M., Allison, M.A., Redline, S., Buxbaum, S.G., Mohlke, K.L., Meulenbelt, I., Ballantyne, C.M., Dedoussis, G.V., Hu, F.B., Liu, Y., Paulweber, B., Spector, T.D., Slagboom, P.E., Ferrucci, L., Jula, A., Perola, M., Raitakari, O., Florez, J.C., Salomaa, V., Eriksson, J.G., Frayling, T.M., Hicks, A.A., Lehtimäki, T., Smith, G.D., Siscovick, D.S., Kronenberg, F., van Duijn, C.M., Loos, R.J., Waterworth, D., Meigs, J.B., Dupuis, J., Richards, J.B., Posthuma, D., Penninx, B.W.J.H., Vogelzangs, N., and Kathiresan, S.
- Abstract
Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10
- Published
- 2012
- Full Text
- View/download PDF
27. Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms
- Author
-
Zhai, G., Teumer, A., Stolk, L., Perry, J.R., Vandenput, L., Coviello, A.D., Koster, A., Bell, J.T., Bhasin, S., Eriksson, J., Eriksson, A., Ernst, F., Ferrucci, L., Frayling, T.M., Glass, D., Grundberg, E., Haring, R., Hedman, A.K., Hofman, A., Kiel, D.P., Kroemer, H.K., Liu, Y., Lunetta, K.L., Maggio, M., Lorentzon, M., Mangino, M., Melzer, D., Miljkovic, I., Nica, A., Penninx, B.W.J.H., Vasan, R.S., Rivadeneira, F., Small, K.S., Soranzo, N., Uitterlinden, A. G., Voelzke, H., Wilson, S.G., Xi, L., Zhuang, W.V., Harris, T.B., Murabito, J.M., Ohlsson, C., Murray, A., de Jong, F.H., Spector, T.D., Wallaschofski, H., Zhai, G., Teumer, A., Stolk, L., Perry, J.R., Vandenput, L., Coviello, A.D., Koster, A., Bell, J.T., Bhasin, S., Eriksson, J., Eriksson, A., Ernst, F., Ferrucci, L., Frayling, T.M., Glass, D., Grundberg, E., Haring, R., Hedman, A.K., Hofman, A., Kiel, D.P., Kroemer, H.K., Liu, Y., Lunetta, K.L., Maggio, M., Lorentzon, M., Mangino, M., Melzer, D., Miljkovic, I., Nica, A., Penninx, B.W.J.H., Vasan, R.S., Rivadeneira, F., Small, K.S., Soranzo, N., Uitterlinden, A. G., Voelzke, H., Wilson, S.G., Xi, L., Zhuang, W.V., Harris, T.B., Murabito, J.M., Ohlsson, C., Murray, A., de Jong, F.H., Spector, T.D., and Wallaschofski, H.
- Abstract
Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10
- Published
- 2011
- Full Text
- View/download PDF
28. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.
- Author
-
Speliotes, E.K., Willer, C.J., Berndt, S.I., Monda, K.L., Thorleifsson, G., Jackson, A., Allen, H.L., Lindgren, C.M., Luan, J., Magi, R., Randall, J., Vedantam, S., Winkler, T.W., Qi, L., Workalemahu, T., Heid, I.M., Steinthorsdottir, V., Stringham, H.M., Weedon, M.N., Wheeler, E., Wood, A.R., Ferreira, T., Weyant, R.J., Segre, A., Estrada, K., Liang, L., Nemesh, J., Park, J., Gustafsson, S., Kilpelainen, T.O., Yang, J., Bouatia-Naji, N., Esko, T., Feitosa, M.F., Kutalik, Z., Mangino, M., Raychaudhuri, S., Scherag, A., Smith, A.V., Welch, R., Zhao, J.H., Aben, K.K.H., Absher, D., Amin, N., Dixon, A.L., Fisher, E., Glazer, N.L., Goddard, M.E., Hoesel, V., Hottenga, J.J., Johansson, A, Johnson, T., Ketkar, S., Lamina, C., Li, S., Moffatt, M.F., Myers, R.H., Narisu, N., Perry, J.R., Peters, M.J., Preuss, M., Ripatti, S., Rivadeneira, F., Sandholt, C., Scott, L.J., Timpson, N.J., Tyrer, J.P., Wingerden, S. van, Watanabe, R.M., White, C.C., Wiklund, F., Barlassina, C., Chasman, D.I., Cooper, M., Jansson, J.O., Lawrence, R.W., Pellikka, N., Prokopenko, I., Shi, J., Thiering, E., Alavere, H., Alibrandi, M.T., Almgren, P., Kiemeney, L.A.L.M., Speliotes, E.K., Willer, C.J., Berndt, S.I., Monda, K.L., Thorleifsson, G., Jackson, A., Allen, H.L., Lindgren, C.M., Luan, J., Magi, R., Randall, J., Vedantam, S., Winkler, T.W., Qi, L., Workalemahu, T., Heid, I.M., Steinthorsdottir, V., Stringham, H.M., Weedon, M.N., Wheeler, E., Wood, A.R., Ferreira, T., Weyant, R.J., Segre, A., Estrada, K., Liang, L., Nemesh, J., Park, J., Gustafsson, S., Kilpelainen, T.O., Yang, J., Bouatia-Naji, N., Esko, T., Feitosa, M.F., Kutalik, Z., Mangino, M., Raychaudhuri, S., Scherag, A., Smith, A.V., Welch, R., Zhao, J.H., Aben, K.K.H., Absher, D., Amin, N., Dixon, A.L., Fisher, E., Glazer, N.L., Goddard, M.E., Hoesel, V., Hottenga, J.J., Johansson, A, Johnson, T., Ketkar, S., Lamina, C., Li, S., Moffatt, M.F., Myers, R.H., Narisu, N., Perry, J.R., Peters, M.J., Preuss, M., Ripatti, S., Rivadeneira, F., Sandholt, C., Scott, L.J., Timpson, N.J., Tyrer, J.P., Wingerden, S. van, Watanabe, R.M., White, C.C., Wiklund, F., Barlassina, C., Chasman, D.I., Cooper, M., Jansson, J.O., Lawrence, R.W., Pellikka, N., Prokopenko, I., Shi, J., Thiering, E., Alavere, H., Alibrandi, M.T., Almgren, P., and Kiemeney, L.A.L.M.
- Abstract
Contains fulltext : 88350.pdf (publisher's version ) (Closed access)
- Published
- 2010
29. Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- Author
-
Lango Allen, H., Estrada, K., Lettre, G., Berndt, S.I., Weedon, M.N., Rivadeneira, F., Willer, C.J., Jackson, A.U., Vedantam, S., Raychaudhuri, S., Ferreira, T., Wood, A.R., Weyant, R.J., Segrè, A.V., Speliotes, E.K., Wheeler, E., Soranzo, N., Park, J.H., Yang, J., Gudbjartsson, D.F., Heard-Costa, N.L., Randall, J., Vernon Smith, A., Mägi, R., Pastinen, T., Liang, L., Heid, I.M., Luan, J., Thorleifsson, G., Winkler, T.W., Goddard, M.E., Sin Lo, K., Palmer, C.N., Workalemahu, T., Aulchenko, Y.S., Johansson, A., Zillikens, M.C., Feitosa, M.F., Esko, T., Johnson, T., Ketkar, S., Kraft, P., Mangino, M., Prokopenko, I., Absher, D., Albrecht, E., Ernst, F., Glazer, N.L., Hayward, C., Hottenga, J.J., Jacobs, K.B., Knowles, J.W., Kutalik, Z., Monda, K.L., Polasek, O., Preuss, M., Rayner, N.W., Robertson, N.R., Steinthorsdottir, V., Tyrer, J.P., Voight, B.F., Wiklund, F., Xu, J., Hua Zhao, J., Nyholt, D.R., Pellikka, N., Perola, M., Perry, J.R., Surakka, I., Tammesoo, M.L., Altmaier, E.L., Aben, K.K.H., Kiemeney, L.A.L.M., Heijer, M. den, Lango Allen, H., Estrada, K., Lettre, G., Berndt, S.I., Weedon, M.N., Rivadeneira, F., Willer, C.J., Jackson, A.U., Vedantam, S., Raychaudhuri, S., Ferreira, T., Wood, A.R., Weyant, R.J., Segrè, A.V., Speliotes, E.K., Wheeler, E., Soranzo, N., Park, J.H., Yang, J., Gudbjartsson, D.F., Heard-Costa, N.L., Randall, J., Vernon Smith, A., Mägi, R., Pastinen, T., Liang, L., Heid, I.M., Luan, J., Thorleifsson, G., Winkler, T.W., Goddard, M.E., Sin Lo, K., Palmer, C.N., Workalemahu, T., Aulchenko, Y.S., Johansson, A., Zillikens, M.C., Feitosa, M.F., Esko, T., Johnson, T., Ketkar, S., Kraft, P., Mangino, M., Prokopenko, I., Absher, D., Albrecht, E., Ernst, F., Glazer, N.L., Hayward, C., Hottenga, J.J., Jacobs, K.B., Knowles, J.W., Kutalik, Z., Monda, K.L., Polasek, O., Preuss, M., Rayner, N.W., Robertson, N.R., Steinthorsdottir, V., Tyrer, J.P., Voight, B.F., Wiklund, F., Xu, J., Hua Zhao, J., Nyholt, D.R., Pellikka, N., Perola, M., Perry, J.R., Surakka, I., Tammesoo, M.L., Altmaier, E.L., Aben, K.K.H., Kiemeney, L.A.L.M., and Heijer, M. den
- Abstract
Contains fulltext : 88266.pdf (publisher's version ) (Closed access)
- Published
- 2010
30. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.
- Author
-
Heid, I.M., Jackson, A.U., Randall, J.C., Winkler, T.W., Qi, L., Steinthorsdottir, V., Thorleifsson, G., Zillikens, M.C., Speliotes, E.K., Mägi, R., Workalemahu, T., White, C.C., Bouatia-Naji, N., Harris, T.B., Berndt, S.I., Ingelsson, E., Willer, C.J., Weedon, M.N., Luan, J., Vedantam, S., Esko, T., Kilpeläinen, T.O., Kutalik, Z., Li, S., Monda, K.L., Dixon, A.L., Holmes, C.C., Kaplan, L.M., Liang, L., Min, J.L., Moffatt, M.F., Molony, C., Nicholson, G., Schadt, E.E., Zondervan, K.T., Feitosa, M.F., Ferreira, T., Allen, H.L., Weyant, R.J., Wheeler, E., Wood, A.R., MAGIC, Estrada, K., Goddard, M.E., Lettre, G., Mangino, M., Nyholt, D.R., Purcell, S., Smith, A.V., Visscher, P.M., Yang, J., McCarroll, S.A., Nemesh, J., Voight, B.F., Absher, D., Amin, N., Aspelund, T., Coin, L., Glazer, N.L., Hayward, C., Heard-Costa, N.L., Hottenga, J.J., Johansson, A., Johnson, T., Kaakinen, M., Kapur, K., Ketkar, S., Knowles, J.W., Kraft, P., Kraja, A.T., Lamina, C., Leitzmann, M.F., McKnight, B., Morris, A.P., Ong, K.K., Perry, J.R., Peters, M.J., Polasek, O., Prokopenko, I., Rayner, N.W., Ripatti, S., Rivadeneira, F., Robertson, N.R., Sanna, S., Sovio, U., Surakka, I., Teumer, A., van Wingerden, S., Vitart, V., Zhao, J.H., Cavalcanti-Proença, C., Chines, P.S., Fisher, E., Kulzer, J.R., Lecoeur, C., Narisu, N., Sandholt, C., Scott, L.J., Silander, K., Stark, K., Tammesoo, M.L., Teslovich, T.M., Timpson, N.J., Watanabe, R.M., Welch, R., Chasman, D.I., Cooper, M.N., Jansson, J.O., Kettunen, J., Lawrence, R.W., Pellikka, N., Perola, M., Vandenput, L., Alavere, H., Almgren, P., Atwood, L.D., Bennett, A.J., Biffar, R., Bonnycastle, L.L., Bornstein, S.R., Buchanan, T.A., Campbell, H., Day, I.N., Dei, M., Dörr, M., Elliott, P., Erdos, M.R., Eriksson, J.G., Freimer, N.B., Fu, M., Gaget, S., Geus, E.J., Gjesing, A.P., Grallert, H., Grässler, J., Groves, C.J., Guiducci, C., Hartikainen, A.L., Hassanali, N., Havulinna, A.S., Herzig, K.H., Hicks, A.A., Hui, J., Igl, W., Jousilahti, P., Jula, A., Kajantie, E., Kinnunen, L., Kolcic, I., Koskinen, S., Kovacs, P., Kroemer, H.K., Krzelj, V., Kuusisto, J., Kvaloy, K., Laitinen, J., Lantieri, O., Lathrop, G.M., Lokki, M.L., Luben, R.N., Ludwig, B., McArdle, W.L., McCarthy, A., Morken, M.A., Nelis, M., Neville, M.J., Paré, G., Parker, A.N., Peden, J.F., Pichler, I., Pietiläinen, K.H., Platou, C.G., Pouta, A., Ridderstråle, M., Samani, N.J., Saramies, J., Sinisalo, J., Smit, J.H., Strawbridge, R.J., Stringham, H.M., Swift, A.J., Teder-Laving, M., Thomson, B., Usala, G., van Meurs, J.B., van Ommen, G.J., Vatin, V., Volpato, C.B., Wallaschofski, H., Walters, G.B., Widen, E., Wild, S.H., Willemsen, G., Witte, D.R., Zgaga, L., Zitting, P., Beilby, J.P., James, A.L., Kähönen, M., Lehtimäki, T., Nieminen, M.S., Ohlsson, C., Palmer, L.J., Raitakari, O., Ridker, P.M., Stumvoll, M., Tönjes, A., Viikari, J., Balkau, B., Ben-Shlomo, Y., Bergman, R.N., Boeing, H., Smith, G.D., Ebrahim, S., Froguel, P., Hansen, T., Hengstenberg, C., Hveem, K., Isomaa, B., Jørgensen, T., Karpe, F., Khaw, K.T., Laakso, M., Lawlor, D.A., Marre, M., Meitinger, T., Metspalu, A., Midthjell, K., Pedersen, O., Salomaa, V., Schwarz, P.E., Tuomi, T., Tuomilehto, J., Valle, T.T., Wareham, N.J., Arnold, A.M., Beckmann, J.S., Bergmann, S., Boerwinkle, E., Boomsma, D.I., Caulfield, M.J., Collins, F.S., Eiriksdottir, G., Gudnason, V., Gyllensten, U., Hamsten, A., Hattersley, A.T., Hofman, A., Hu, F.B., Illig, T., Iribarren, C., Jarvelin, M.R., Kao, W.H., Kaprio, J., Launer, L.J., Munroe, P.B., Oostra, B., Penninx, B.W., Pramstaller, P.P., Psaty, B.M., Quertermous, T., Rissanen, A., Rudan, I., Shuldiner, A.R., Soranzo, N., Spector, T.D., Syvanen, A.C., Uda, M., Uitterlinden, A., Völzke, H., Vollenweider, P., Wilson, J.F., Witteman, J.C., Wright, A.F., Abecasis, G.R., Boehnke, M., Borecki, I.B., Deloukas, P., Frayling, T.M., Groop, L.C., Haritunians, T., Hunter, D.J., Kaplan, R.C., North, K.E., O'Connell, J.R., Peltonen, L., Schlessinger, D., Strachan, D.P., Hirschhorn, J.N., Assimes, T.L., Wichmann, H.E., Thorsteinsdottir, U., van Duijn, C.M., Stefansson, K., Cupples, L.A., Loos, R.J., Barroso, I., McCarthy, M.I., Fox, C.S., Mohlke, K.L., Lindgren, C.M., Heid, I.M., Jackson, A.U., Randall, J.C., Winkler, T.W., Qi, L., Steinthorsdottir, V., Thorleifsson, G., Zillikens, M.C., Speliotes, E.K., Mägi, R., Workalemahu, T., White, C.C., Bouatia-Naji, N., Harris, T.B., Berndt, S.I., Ingelsson, E., Willer, C.J., Weedon, M.N., Luan, J., Vedantam, S., Esko, T., Kilpeläinen, T.O., Kutalik, Z., Li, S., Monda, K.L., Dixon, A.L., Holmes, C.C., Kaplan, L.M., Liang, L., Min, J.L., Moffatt, M.F., Molony, C., Nicholson, G., Schadt, E.E., Zondervan, K.T., Feitosa, M.F., Ferreira, T., Allen, H.L., Weyant, R.J., Wheeler, E., Wood, A.R., MAGIC, Estrada, K., Goddard, M.E., Lettre, G., Mangino, M., Nyholt, D.R., Purcell, S., Smith, A.V., Visscher, P.M., Yang, J., McCarroll, S.A., Nemesh, J., Voight, B.F., Absher, D., Amin, N., Aspelund, T., Coin, L., Glazer, N.L., Hayward, C., Heard-Costa, N.L., Hottenga, J.J., Johansson, A., Johnson, T., Kaakinen, M., Kapur, K., Ketkar, S., Knowles, J.W., Kraft, P., Kraja, A.T., Lamina, C., Leitzmann, M.F., McKnight, B., Morris, A.P., Ong, K.K., Perry, J.R., Peters, M.J., Polasek, O., Prokopenko, I., Rayner, N.W., Ripatti, S., Rivadeneira, F., Robertson, N.R., Sanna, S., Sovio, U., Surakka, I., Teumer, A., van Wingerden, S., Vitart, V., Zhao, J.H., Cavalcanti-Proença, C., Chines, P.S., Fisher, E., Kulzer, J.R., Lecoeur, C., Narisu, N., Sandholt, C., Scott, L.J., Silander, K., Stark, K., Tammesoo, M.L., Teslovich, T.M., Timpson, N.J., Watanabe, R.M., Welch, R., Chasman, D.I., Cooper, M.N., Jansson, J.O., Kettunen, J., Lawrence, R.W., Pellikka, N., Perola, M., Vandenput, L., Alavere, H., Almgren, P., Atwood, L.D., Bennett, A.J., Biffar, R., Bonnycastle, L.L., Bornstein, S.R., Buchanan, T.A., Campbell, H., Day, I.N., Dei, M., Dörr, M., Elliott, P., Erdos, M.R., Eriksson, J.G., Freimer, N.B., Fu, M., Gaget, S., Geus, E.J., Gjesing, A.P., Grallert, H., Grässler, J., Groves, C.J., Guiducci, C., Hartikainen, A.L., Hassanali, N., Havulinna, A.S., Herzig, K.H., Hicks, A.A., Hui, J., Igl, W., Jousilahti, P., Jula, A., Kajantie, E., Kinnunen, L., Kolcic, I., Koskinen, S., Kovacs, P., Kroemer, H.K., Krzelj, V., Kuusisto, J., Kvaloy, K., Laitinen, J., Lantieri, O., Lathrop, G.M., Lokki, M.L., Luben, R.N., Ludwig, B., McArdle, W.L., McCarthy, A., Morken, M.A., Nelis, M., Neville, M.J., Paré, G., Parker, A.N., Peden, J.F., Pichler, I., Pietiläinen, K.H., Platou, C.G., Pouta, A., Ridderstråle, M., Samani, N.J., Saramies, J., Sinisalo, J., Smit, J.H., Strawbridge, R.J., Stringham, H.M., Swift, A.J., Teder-Laving, M., Thomson, B., Usala, G., van Meurs, J.B., van Ommen, G.J., Vatin, V., Volpato, C.B., Wallaschofski, H., Walters, G.B., Widen, E., Wild, S.H., Willemsen, G., Witte, D.R., Zgaga, L., Zitting, P., Beilby, J.P., James, A.L., Kähönen, M., Lehtimäki, T., Nieminen, M.S., Ohlsson, C., Palmer, L.J., Raitakari, O., Ridker, P.M., Stumvoll, M., Tönjes, A., Viikari, J., Balkau, B., Ben-Shlomo, Y., Bergman, R.N., Boeing, H., Smith, G.D., Ebrahim, S., Froguel, P., Hansen, T., Hengstenberg, C., Hveem, K., Isomaa, B., Jørgensen, T., Karpe, F., Khaw, K.T., Laakso, M., Lawlor, D.A., Marre, M., Meitinger, T., Metspalu, A., Midthjell, K., Pedersen, O., Salomaa, V., Schwarz, P.E., Tuomi, T., Tuomilehto, J., Valle, T.T., Wareham, N.J., Arnold, A.M., Beckmann, J.S., Bergmann, S., Boerwinkle, E., Boomsma, D.I., Caulfield, M.J., Collins, F.S., Eiriksdottir, G., Gudnason, V., Gyllensten, U., Hamsten, A., Hattersley, A.T., Hofman, A., Hu, F.B., Illig, T., Iribarren, C., Jarvelin, M.R., Kao, W.H., Kaprio, J., Launer, L.J., Munroe, P.B., Oostra, B., Penninx, B.W., Pramstaller, P.P., Psaty, B.M., Quertermous, T., Rissanen, A., Rudan, I., Shuldiner, A.R., Soranzo, N., Spector, T.D., Syvanen, A.C., Uda, M., Uitterlinden, A., Völzke, H., Vollenweider, P., Wilson, J.F., Witteman, J.C., Wright, A.F., Abecasis, G.R., Boehnke, M., Borecki, I.B., Deloukas, P., Frayling, T.M., Groop, L.C., Haritunians, T., Hunter, D.J., Kaplan, R.C., North, K.E., O'Connell, J.R., Peltonen, L., Schlessinger, D., Strachan, D.P., Hirschhorn, J.N., Assimes, T.L., Wichmann, H.E., Thorsteinsdottir, U., van Duijn, C.M., Stefansson, K., Cupples, L.A., Loos, R.J., Barroso, I., McCarthy, M.I., Fox, C.S., Mohlke, K.L., and Lindgren, C.M.
- Abstract
Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
- Published
- 2010
31. Kurdish Culture and Society: an Annotated Bibliography
- Author
-
Perry, J.R.
- Subjects
Kurdish Culture and Society: an Annotated Bibliography (Book) -- Book reviews ,Books -- Book reviews - Published
- 2004
32. The right people help you do business in a way that's better, faster and cheaper. (Straight Talk/Letters)
- Author
-
Perry, J.R., Jay
- Subjects
Automobile industry ,Business - Abstract
Regardless of what business we are in, we will always be challenged with a common task: To provide products or services better, faster and cheaper. If you look at any [...]
- Published
- 2003
33. Communication: The most important part of leadership. (Straight Talk)
- Author
-
Perry, J.R.
- Subjects
Automobile repair shops -- Management ,Business communication -- Methods ,Automobile industry ,Business - Abstract
J.R.(Jay) Perry For company leaders today, time is incredibly valuable. This means the most important challenge is to more effectively use the resources available. To accomplish this, good communication is [...]
- Published
- 2001
34. Performance Features for a PACS Display Console
- Author
-
Perry, J.R., Thompson, B.G., Staab, E.V., Pizer, S.M., and Johnston, R.E.
- Subjects
Archival Storage ,Radiology ,Medical Records ,Specifications ,Hospital Information Systems ,Displays ,User Interface - Published
- 1983
35. Challenges in the design and conduct of phase III brain tumor therapy trials.
- Author
-
Perry, J.R. and DeAngelis, L.M.
- Published
- 1997
- Full Text
- View/download PDF
36. An evaluation of the effectiveness of adaptive histogram equalization for contrast enhancement.
- Author
-
Zimmerman, J.B., Pizer, S.M., Staab, E.V., Perry, J.R., McCartney, W., and Brenton, B.C.
- Published
- 1988
- Full Text
- View/download PDF
37. Synthetic Aperture Radar Imaging of Ship-Generated Internal-Waves During the Uk-Us Loch Linnhe Series of Experiments.
- Author
-
Stapleton, N.R. and Perry, J.R.
- Published
- 1992
- Full Text
- View/download PDF
38. MAKING THEMARKET IN PENSION PORTFOLIOS
- Author
-
PERRY, J.R.
- Subjects
Pensions -- Investments ,Investments -- Management ,Banking, finance and accounting industries ,Business ,Human resources and labor relations - Published
- 1979
39. Phoridae (Diptera) from English pasture soils
- Author
-
Disney, R.H.L.., Henderson, I.F.., Perry, J.R.., and Clements, R.O..
- Published
- 1981
- Full Text
- View/download PDF
40. L. P. ELWELL-SUTTON, The Persian Metres, Cambridge, Cambridge University Press 1976. Pp. xiv, 285, £ 9
- Author
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Perry, J.R.
- Published
- 1978
- Full Text
- View/download PDF
41. History - John E. Woods, The Aqquyunlu; Clan. Confederation. Empire (Minneapolis, Bibliotheca Islamica, 1976). Pp. 348 – xvi. Maps, tables, plates. $20.00.
- Author
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Perry, J.R., primary
- Published
- 1977
- Full Text
- View/download PDF
42. Body electricity
- Author
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Perry, J.R., primary
- Published
- 1934
- Full Text
- View/download PDF
43. Synthetic Aperture Radar Imaging of Ship-Generated Internal-Waves During the Uk-Us Loch Linnhe Series of Experiments
- Author
-
Stapleton, N.R., primary and Perry, J.R., additional
- Full Text
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44. Iranian Cities (Book Review).
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Perry, J.R.
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CITIES & towns ,NONFICTION - Abstract
Reviews the book 'Iranian Cities,' by Heinz Gaube.
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- 1980
- Full Text
- View/download PDF
45. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance
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John R. B. Perry, James B. Meigs, José Dupuis, Luigi Ferrucci, Johan G. Eriksson, Vilmundur Gudnason, Eric J.G. Sijbrands, Jeanette S. Andrews, Jonna L. Grimsby, Lawrence F. Bielak, Peter Kovacs, Panos Deloukas, Marijana Peričić, Johannes H. Smit, Ruth J. F. Loos, Gonneke Willemsen, Eric Boerwinkle, Ben A. Oostra, Manuel Serrano-Ríos, Alena Stančáková, Meena Kumari, Antti Jula, Michael Marmot, Caroline S. Fox, Simon Heath, Guo Li, Ola Hansson, Gerard Waeber, Anne U. Jackson, Nicholas L. Smith, Markku Laakso, George Dedoussis, Aarno Palotie, Sara M. Willems, John F. Peden, Elisabeth Widen, Caroline Hayward, Alan F. Wright, Claes Ladenvall, May E. Montasser, María Teresa Martínez-Larrad, Peter Vollenweider, Louis Pérusse, Tamara B. Harris, Wen Hong L. Kao, Danijela Budimir, Denis Rybin, David B. Savage, Michael A. Province, Alisa K. Manning, Bruna Gigante, Najaf Amin, Lenore J. Launer, Naveed Sattar, Lori L. Bonnycastle, Göran Hallmans, Jeffrey R. O'Connell, Stéphane Lobbens, Jacques S. Beckmann, Gemma Cadby, J. Wouter Jukema, Maria Dimitriou, Michael Stumvoll, Max Vikström, Rona J. Strawbridge, Hugh Watkins, Lyle J. Palmer, Johanna Kuusisto, Aimo Ruokonen, Hanieh Yaghootkar, Yan V. Sun, Inês Barroso, Amy J. Swift, Nancy L. Pedersen, Lars Lind, Mladen Boban, Nita G. Forouhi, Ken K. Ong, Ivana Kolcic, Anke Tönjes, Timothy M. Frayling, Paul W. Franks, Narisu Narisu, Karin Leander, Serge Hercberg, Diana Zelenika, Sharon L.R. Kardia, Min A. Jhun, Marjo-Riitta Järvelin, Stella Trompet, Jaakko Kaprio, Toshiko Tanaka, David S. Siscovick, Toby Johnson, Cornelia M. van Duijn, Veikko Salomaa, Jose C. Florez, James F. Wilson, Leena Peltonen, Pilar Galan, Robert Clarke, Andrew A. Hicks, Claudia Langenberg, Anders Hamsten, David Couper, Albert Hofman, Dawn M. Waterworth, John Blangero, James S. Pankow, Nabila Bouatia-Naji, Sirkka Keinänen-Kiukaanniemi, Mark I. McCarthy, Valeriya Lyssenko, Leif Groop, Brenda W.J.H. Penninx, Ching-Ti Liu, Anuj Goel, Marina Pehlić, Michael Boehnke, Mika Kivimäki, Maria Sabater-Lleal, Emil Rehnberg, Ingrid B. Borecki, Ozren Polasek, Eco J. C. de Geus, Peter P. Pramstaller, Igor Rudan, Richard M. Watanabe, Pierre Meneton, Iva Miljkovic, Vincent Mooser, G. Mark Lathrop, John Beilby, Laura J. Rasmussen-Torvik, Arturo Corbató-Anchuelo, Yvonne Böttcher, Richard N. Bergman, Daniel R. Barnes, Paul C. D. Johnson, Mustafa Atalay, Aroon D. Hingorani, Olga D. Carlson, Perttu Salo, Jacqueline C.M. Witteman, Udo Seedorf, Timo Saaristo, Jian'an Luan, Nicholas J. Wareham, Gudny Eiriksdottir, Matti Uusitupa, Yongmei Liu, Jaakko Tuomilehto, Yurii S. Aulchenko, Peter Schwarz, Robert A. Scott, Lina Zgaga, Joseph Hung, Reedik Mägi, Maria Grazia Franzosi, Eric J. Brunner, Claude Bouchard, Ian Ford, Francis S. Collins, Ulf de Faire, Benjamin F. Voight, Erik Ingelsson, Mario A. Morken, Stefania Bandinelli, Nicole L. Glazer, Dmitry Shungin, Lars Lannfelt, André G. Uitterlinden, Tatijana Zemunik, Markus Perola, Kenneth Rice, Veronique Vitart, Kerrin S. Small, Jouke-Jan Hottenga, Han Chen, Jerome I. Rotter, Philippe Froguel, Karen L. Mohlke, Marie-Claude Vohl, Dorret I. Boomsma, Harry Campbell, Peter S. Chines, Pau Navarro, Vasiliki Lagou, Albert V. Smith, Kathleen Stirrups, Josephine M. Egan, Alan R. Shuldiner, Katri Räikkönen, Inga Prokopenko, Ping An, Rainer Rauramaa, Beverley Balkau, Thor Aspelund, Eleanor Wheeler, Mariza de Andrade, Richa Saxena, Jari Lahti, Cécile Lecoeur, Timo A. Lakka, Jennie Hui, Michael R. Erdos, Stavroula Kanoni, Kirsten Ohm Kyvik, Bengt Sennblad, Sarah H. Wild, Patricia A. Peyser, Patrik K. E. Magnusson, Claire Bellis, Elodie Eury, Jaana Lindström, Boston University [Boston] (BU), Broad Institute of Harvard and MIT, Partenaires INRAE, Massachusetts General Hospital, Massachusetts General Hospital [Boston], Department of Genetics [Boston], Harvard Medical School [Boston] (HMS), Department of Medicine, Université de Sherbrooke (UdeS), Addenbrooke's Hospital, Harvard Medical School [Boston] (HMS)-Beth Israel Deaconess Medical Center [Boston] (BIDMC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Université Lille Nord de France (COMUE), Department of Epidemiology, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-Center for Social Epidemiology and Population Health, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford [Oxford], The Wellcome Trust Centre for Human Genetics [Oxford], The Netherlands Cancer Institute, Ontario Institute for Cancer Research, Mount Sinai Hospital [Toronto, Canada] (MSH), VU University Amsterdam, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Michigan System, Queen Mary University of London (QMUL), The Wellcome Trust Sanger Institute [Cambridge], Lund University [Lund], Diabetes Centre, Lund University, University of Helsinki, Wake Forest School of Medicine, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, University of Maryland School of Medicine, University of Maryland System, University of Edinburgh, University of Exeter, Department of Twin Research and Genetic Epidemiology, King's College London, London, Northwestern University [Evanston], National Institute of Health and Welfare, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Lund University Diabetes Centre, Umeå University, National Institutes of Health, Centre for Medical Systems Biology, Netherlands Genomics Initiative, Washington University in Saint Louis (WUSTL), Department of Health Sciences Research, Mayo Clinic, Wake Forest University, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, University of Iceland, Institute of Biomedicine, Physiology, University of Eastern Finland, Institut National de la Santé et de la Recherche Médicale (INSERM), UMR S 1018, Université Paris-Sud - Paris 11 (UP11), Azienda Sanitaria Firenze, Department of Medical Genetics, Université de Lausanne (UNIL), Centre Hospitalier Universitaire Vaudois (CHUV), Queen Elizabeth II Medical Centre, Research Institute, University of Southern California (USC), University of Split, The University of Texas Health Science Center at Houston (UTHealth), Leipzig University, Pennington Biomedical Research Center, Department of Epidemiology & Public Health, University College of London [London] (UCL), San Carlos Clinical Hospital, University of North Carolina, Harokopio University, National Institute on Aging, Folkhälsan Research Centre, Vaasa Central Hospital, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Psychiatry, EMGO - Lifestyle, overweight and diabetes, Epidemiology, Immunology, Erasmus School of Social and Behavioural Sciences, Clinical Genetics, Ophthalmology, Internal Medicine, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Multiple Tissue Human Expression Resource (MUTHER) Consortium, Ahmadi, K.R., Ainali, C., Barrett, A., Bataille, V., Bell, J.T., Buil, A., Deloukas, P., Dermitzakis, E.T., Dimas, A.S., Durbin, R., Glass, D., Grundberg, E., Hassanali, N., Hedman, Å.K., Ingle, C., Knowles, D., Krestyaninova, M., Lindgren, C.M., Lowe, C.E., McCarthy, M.I., Meduri, E., di Meglio, P., Min, J.L., Montgomery, S.B., Nestle, F.O., Nica, A.C., Nisbet, J., O'Rahilly, S., Parts, L., Potter, S., Sekowska, M., Shin, S.Y., Small, K.S., Soranzo, N., Spector, T.D., Surdulescu, G., Travers, M.E., Tsaprouni, L., Tsoka, S., Wilk, A., Yang, T.P., Zondervan, K.T., Voight, B.F., Scott, L.J., Steinthorsdottir, V., Morris, A.P., Dina, C., Welch, R.P., Zeggini, E., Huth, C., Aulchenko, Y.S., Thorleifsson, G., McCulloch, L.J., Ferreira, T., Grallert, H., Amin, N., Wu, G., Willer, C.J., Raychaudhuri, S., McCarroll, S.A., Langenberg, C., Hofmann, O.M., Dupuis, J., Qi, L., Segrè, A.V., van Hoek, M., Navarro, P., Ardlie, K., Balkau, B., Benediktsson, R., Bennett, A.J., Blagieva, R., Boerwinkle, E., Bonnycastle, L.L., Boström, K.B., Bravenboer, B., Bumpstead, S., Burtt, N.P., Charpentier, G., Chines, P.S., Cornelis, M., Couper, D.J., Crawford, G., Doney, A.S., Elliott, K.S., Elliott, A.L., Erdos, M.R., Fox, C.S., Franklin, C.S., Ganser, M., Gieger, C., Grarup, N., Green, T., Griffin, S., Groves, C.J., Guiducci, C., Hadjadj, S., Herder, C., Isomaa, B., Jackson, A.U., Johnson, P.R., Jørgensen, T., Kao, W.H., Klopp, N., Kong, A., Kraft, P., Kuusisto, J., Lauritzen, T., Li, M., Lieverse, A., Lyssenko, V., Marre, M., Meitinger, T., Midthjell, K., Morken, M.A., Narisu, N., Nilsson, P., Owen, K.R., Payne, F., Perry, J.R., Petersen, A.K., Platou, C., Proença, C., Prokopenko, I., Rathmann, W., Rayner, N.W., Robertson, N.R., Rocheleau, G., Roden, M., Sampson, M.J., Saxena, R., Shields, B.M., Shrader, P., Sigurdsson, G., Sparsø, T., Strassburger, K., Stringham, H.M., Sun, Q., Swift, A.J., Thorand, B., Tichet, J., Tuomi, T., van Dam, R.M., van Haeften, T.W., van Herpt, T., van Vliet-Ostaptchouk, J.V., Walters, G.B., Weedon, M.N., Wijmenga, C., Witteman, J., Bergman, R.N., Cauchi, S., Collins, F.S., Gloyn, A.L., Gyllensten, U., Hansen, T., Hide, W.A., Hitman, G.A., Hofman, A., Hunter, D.J., Hveem, K., Laakso, M., Mohlke, K.L., Morris, A.D., Palmer, C.N., Pramstaller, P.P., Rudan, I., Sijbrands, E., Stein, L.D., Tuomilehto, J., Uitterlinden, A., Walker, M., Wareham, N.J., Watanabe, R.M., Abecasis, G.R., Boehm, B.O., Campbell, H., Daly, M.J., Hattersley, A.T., Hu, F.B., Meigs, J.B., Pankow, J.S., Pedersen, O., Wichmann, H.E., Barroso, I., Florez, J.C., Frayling, T.M., Groop, L., Sladek, R., Thorsteinsdottir, U., Wilson, J.F., Illig, T., Froguel, P., van Duijn, C.M., Stefansson, K., Altshuler, D., Boehnke, M., Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA)
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Blood Glucose ,Netherlands Twin Register (NTR) ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,LOCI ,Genome-wide association study ,Type 2 diabetes ,SUSCEPTIBILITY ,Body Mass Index ,GLUCOSE ,Blood Glucose/metabolism ,Cholesterol, HDL/metabolism ,Diabetes Mellitus, Type 2/genetics ,Genome-Wide Association Study ,Humans ,Insulin/metabolism ,Insulin Resistance/genetics ,Polymorphism, Single Nucleotide ,0302 clinical medicine ,Insulin ,2. Zero hunger ,Genetics ,0303 health sciences ,COMMON VARIANTS ,3. Good health ,ENVIRONMENT INTERACTION ,OBESITY ,CORONARY-ARTERY-DISEASE ,medicine.medical_specialty ,030209 endocrinology & metabolism ,Accounting ,Biology ,Article ,03 medical and health sciences ,Insulin resistance ,SDG 3 - Good Health and Well-being ,Internal medicine ,Diabetes mellitus ,medicine ,030304 developmental biology ,Genetic association ,Glycemic ,loci ,SNP ,insulin ,business.industry ,Cholesterol, HDL ,medicine.disease ,Obesity ,POLYMORPHISM ,ASSOCIATION ANALYSIS ,Endocrinology ,Diabetes Mellitus, Type 2 ,TYPE-2 DIABETES RISK ,Insulin Resistance ,business - Abstract
Group Authors : DIAGRAM Consortium MUTHER Consortium variants influencing fasting glycemic traits and insulin resistance Seuls les 100 premiers auteurs ont été conservés dans la publication. La liste complète des auteurs et des des affiliations est disponible sur la publication https://www.nature.com/articles/ng.2274.pdf p. 667-669.; International audience; Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 x 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.
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- 2012
46. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts
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Benjamin Voight, Guillaume Pare, Ruth Loos, Michael Preuss, Åsa Johansson, Eco De Geus, Michael Weedon, Marjo-Riitta Jarvelin, Joyce Van Meurs, Torben Jørgensen, Kirsi Pietiläinen, Nicole Glazer, Mattias Lorentzon, Braxton Mitchell, Nicole Soranzo, Patricia Munroe, Ozren Polasek, Elisabeth Thiering, Marika Kaakinen, Carla Vogel, Jennie Hui, Elina Hypponen, ROBERTO ELOSUA, Amanda Bennett, Michael Stumvoll, Andrew Hattersley, Peter P Pramstaller, Lambertus Kiemeney, Sophie Visvikis-Siest, Vilmundur Gudnason, John Whittaker, Aroon Hingorani, Thor Aspelund, Dale Nyholt, Mary Feitosa, Vimal Karani, Mika Kähönen, Lachlan Coin, Malcolm Dunlop, Josee Dupuis, Terho Lehtimäki, Peter Visscher, Katja Aben, Daniel Witte, Cyrus Cooper, Stefan Pilz, Willem Ouwehand, Eleanor Wheeler, Peter Kovacs, Debbie A Lawlor, Kevin Jacobs, Evropi Theodoratou, Hana Lango Allen, Rosanda Mulic, Rui Li, Stephen Kritchevsky, Philippe Froguel, Soumya Raychaudhuri, Cornelia Van Duijn, Andrew Wood, Chiara Lanzani, Tonu Esko, Sadaf Farooqi, Reedik Mägi, Gerard Waeber, Claes Ohlsson, André Scherag, Marcus Kleber, Thomas Meitinger, Lina Zgaga, Denise Houston, Karl Michaëlsson, Robert Weyant, Thomas Wang, Paul Elliott, Robert Luben, Albert Vernon Smith, MANUELA UDA, Gonneke Willemsen, Mark McCarthy, Cecilia Lindgren, Olle Melander, Igor Rudan, Maris Teder-Laving, Liesbeth Vandenput, Vimaleswaran, K, Berry, Dj, Lu, C, Tikkanen, E, Pilz, S, Hiraki, Lt, Cooper, Jd, Dastani, Z, Li, R, Houston, Dk, Wood, Ar, Michaëlsson, K, Vandenput, L, Zgaga, L, YERGES ARMSTRONG, Lm, Mccarthy, Mi, Dupuis, J, Kaakinen, M, Kleber, Me, Jameson, K, Arden, N, Raitakari, O, Viikari, J, Lohman, Kk, Ferrucci, L, Melhus, H, Ingelsson, E, Byberg, L, Lind, L, Lorentzon, M, Salomaa, V, Campbell, H, Dunlop, M, Mitchell, Bd, Herzig, Kh, Pouta, A, Hartikainen, Al, Manunta, Paolo, Streeten, Ea, Theodoratou, E, Jula, A, Wareham, Nj, Ohlsson, C, Frayling, Tm, Kritchevsky, Sb, Spector, Td, Richards, Jb, Lehtimäki, T, Ouwehand, Wh, Kraft, P, Cooper, C, März, W, Power, C, Loos, Rj, Wang, Tj, Järvelin, Mr, Whittaker, Jc, Hingorani, Ad, Hyppönen, E., Council, Medical Research, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Institute for Molecular Medicine Finland, Haartman Institute (-2014), Transplantation Laboratory, Vimaleswaran, Karani S, Berry, Diane J, Lu, Chen, Tikkanen, Emmi, Hyppönen, Elina, Genetic Investigation of Anthropometric Traits (GIANT) Consortium, Hinney, Anke (Beitragende*r), Scherag, Susann (Beitragende*r), Hebebrand, Johannes (Beitragende*r), Epidemiology and Data Science, Psychiatry, EMGO - Lifestyle, overweight and diabetes, Genetic Investigation of Anthropometric Traits-GIANT Consortium, Speliotes, E.K., Willer, C.J., Berndt, S.I., Monda, K.L., Thorleifsson, G., Jackson, A.U., Allen, H.L., Lindgren, C.M., Jian'an, L., Mägi, R., Randall, J.C., Vedantam, S., Winkler, T.W., Qi, L., Workalemahu, T., Heid, I.M., Steinthorsdottir, V., Stringham, H.M., Weedon, M.N., Wheeler, E., Wood, A.R., Ferreira, T., Weyant, R.J., Segrè, A.V., Estrada, K., Liang, L., Nemesh, J., Park, J.H., Gustafsson, S., Kilpeläinen, T.O., Yang, J., Bouatia-Naji, N., Tõnu, E., Feitosa, M.F., Kutalik, Z., Mangino, M., Raychaudhuri, S., Scherag, A., Smith, A.V., Welch, R., Zhao, J.H., Aben, K.K., Absher, D.M., Amin, N., Dixon, A.L., Fisher, E., Glazer, N.L., Goddard, M.E., Heard-Costa, N.L., Hoesel, V., Hottenga, J.J., Johansson, Å., Johnson, T., Ketkar, S., Lamina, C., Li, S., Moffatt, M.F., Myers, R.H., Narisu, N., Perry, J.R., Peters, M.J., Preuss, M., Ripatti, S., Rivadeneira, F., Sandholt, C., Scott, L.J., Timpson, N.J., Tyrer, J.P., van Wingerden, S., Watanabe, R.M., White, C.C., Wiklund, F., Barlassina, C., Chasman, D.I., Cooper, M.N., Jansson, J.O., Lawrence, R.W., Pellikka, N., Prokopenko, I., Shi, J., Thiering, E., Alavere, H., Alibrandi, M.T., Almgren, P., Arnold, A.M., Aspelund, T., Atwood, L.D., Balkau, B., Balmforth, A.J., Bennett, A.J., Ben-Shlomo, Y., Bergman, R.N., Bergmann, S., Biebermann, H., Blakemore, A.I., Boes, T., Bonnycastle, L.L., Bornstein, S.R., Brown, M.J., Buchanan, T.A., Busonero, F., Campbell, H., Cappuccio, F.P., Cavalcanti-Proença, C., Chen, Y.D., Chen, C.M., Chines, P.S., Clarke, R., Coin, L., Connell, J., Day, I.N., Heijer, M., Duan, J., Ebrahim, S., Elliott, P., Elosua, R., Eiriksdottir, G., Erdos, M.R., Eriksson, J.G., Facheris, M.F., Felix, S.B., Fischer-Posovszky, P., Folsom, A.R., Friedrich, N., Freimer, N.B., Fu, M., Gaget, S., Gejman, P.V., Geus, E.J., Gieger, C., Gjesing, A.P., Goel, A., Goyette, P., Grallert, H., Gräßler, J., Greenawalt, D.M., Groves, C.J., Gudnason, V., Guiducci, C., Hartikainen, A.L., Hassanali, N., Hall, A.S., Havulinna, A.S., Hayward, C., Heath, A.C., Hengstenberg, C., Hicks, A.A., Hinney, A., Hofman, A., Homuth, G., Hui, J., Igl, W., Iribarren, C., Isomaa, B., Jacobs, K.B., Jarick, I., Jewell, E., John, U., Jørgensen, T., Jousilahti, P., Jula, A., Kaakinen, M., Kajantie, E., Kaplan, L.M., Kathiresan, S., Kettunen, J., Kinnunen, L., Knowles, J.W., Kolcic, I., König, I.R., Koskinen, S., Kovacs, P., Kuusisto, J., Kraft, P., Kvaløy, K., Laitinen, J., Lantieri, O., Lanzani, C., Launer, L.J., Lecoeur, C., Lehtimäki, T., Lettre, G., Liu, J., Lokki, M.L., Lorentzon, M., Luben, R.N., Ludwig, B., Manunta, P., Marek, D., Marre, M., Martin, N.G., McArdle, W.L., McCarthy, A., McKnight, B., Meitinger, T., Melander, O., Meyre, D., Midthjell, K., Montgomery, G.W., Morken, M.A., Morris, A.P., Mulic, R., Ngwa, J.S., Nelis, M., Neville, M.J., Nyholt, D.R., O'Donnell, C.J., O'Rahilly, S., Ong, K.K., Oostra, B., Paré, G., Parker, A.N., Perola, M., Pichler, I., Pietiläinen, K.H., Platou, C.G., Polasek, O., Pouta, A., Rafelt, S., Raitakari, O., Rayner, N.W., Ridderstråle, M., Rief, W., Ruokonen, A., Robertson, N.R., Rzehak, P., Salomaa, V., Sanders, A.R., Sandhu, M.S., Sanna, S., Saramies, J., Savolainen, M.J., Scherag, S., Schipf, S., Schreiber, S., Schunkert, H., Silander, K., Sinisalo, J., Siscovick, D.S., Smit, J.H., Soranzo, N., Sovio, U., Stephens, J., Surakka, I., Swift, AJ., Tammesoo, M.L., Tardif, J.C., Teder-Laving, M., Teslovich, T.M., Thompson, J.R., Thomson, B., Tönjes, A., Tuomi, T., van Meurs, J.B., van Ommen, G.J., Vatin, V., Viikari, J., Visvikis-Siest, S., Vitart, V., Vogel, C.I., Voight, B.F., Waite, L.L., Wallaschofski, H., Walters, G.B., Widen, E., Wiegand, S., Wild, S.H., Willemsen, G., Witte, D.R., Witteman, J.C., Xu, J., Zhang, Q., Zgaga, L., Ziegler, A., Zitting, P., Beilby, J.P., Farooqi, I.S., Hebebrand, J., Huikuri, H.V., James, AL., Kähönen, M., Levinson, D.F., Macciardi, F., Nieminen, M.S., Ohlsson, C., Palmer, L.J., Ridker, P.M., Stumvoll, M., Beckmann, J.S., Boeing, H., Boerwinkle, E., Boomsma, D.I., Caulfield, M.J., Chanock, S.J., Collins, F.S., Cupples, L.A., Smith, G.D., Erdmann, J., Froguel, P., Grönberg, H., Gyllensten, U., Hall, P., Hansen, T., Harris, T.B., Hattersley, A.T., Hayes, R.B., Heinrich, J., Hu, F.B., Hveem, K., Illig, T., Jarvelin, M.R., Kaprio, J., Karpe, F., Khaw, K.T., Kiemeney, L.A., Krude, H., Laakso, M., Lawlor, D.A., Metspalu, A., Munroe, P.B., Ouwehand, W.H., Pedersen, O., Penninx, B.W., Peters, A., Pramstaller, P.P., Quertermous, T., Reinehr, T., Rissanen, A., Rudan, I., Samani, N.J., Schwarz, P.E., Shuldiner, A.R., Spector, T.D., Tuomilehto, J., Uda, M., Uitterlinden, A., Valle, T.T., Wabitsch, M., Waeber, G., Wareham, N.J., Watkins, H., Wilson, J.F., Wright, A.F., Zillikens, M.C., Chatterjee, N., McCarroll, S.A., Purcell, S., Schadt, E.E., Visscher, P.M., Assimes, T.L., Borecki, I.B., Deloukas, P., Fox, C.S., Groop, L.C., Haritunians, T., Hunter, D.J., Kaplan, R.C., Mohlke, K.L., O'Connell, J.R., Peltonen, L., Schlessinger, D., Strachan, D.P., van Duijn, C.M., Wichmann, H.E., Frayling, T.M., Thorsteinsdottir, U., Abecasis, G.R., Barroso, I., Boehnke, M., Stefansson, K., North, K.E., McCarthy, M.I., Hirschhorn, J.N., Ingelsson, E., Loos, R.J., Medical Research Council (MRC), and National Institute for Health Research
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Male ,Netherlands Twin Register (NTR) ,Medicin och hälsovetenskap ,obesity ,25-HYDROXYVITAMIN D ,D INSUFFICIENCY ,Epidemiology ,Medizin ,vitamin D ,Aetiology, screening and detection [ONCOL 5] ,Medical and Health Sciences ,Gastroenterology ,Body Mass Index ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,GENETIC-VARIANTS ,Medicine ,030212 general & internal medicine ,Vitamin D ,2. Zero hunger ,Genetics ,Aged, 80 and over ,Evidence-Based Medicine ,Confounding ,11 Medical And Health Sciences ,General Medicine ,Middle Aged ,3. Good health ,PREVALENCE ,Europe ,Phenotype ,Genetic Epidemiology ,Biological Markers ,Female ,Life Sciences & Biomedicine ,Research Article ,Vitamin ,Adult ,medicine.medical_specialty ,vitamin D deficiency ,genetic variants ,Genetic Investigation of Anthropometric Traits-GIANT Consortium ,European Continental Ancestry Group ,030209 endocrinology & metabolism ,Single-nucleotide polymorphism ,body mass index ,Polymorphism, Single Nucleotide ,Risk Assessment ,White People ,COMMON OBESITY ,03 medical and health sciences ,D DEFICIENCY ,Medicine, General & Internal ,SDG 3 - Good Health and Well-being ,General & Internal Medicine ,Internal medicine ,Mendelian randomization ,Vitamin D and neurology ,INSTRUMENTAL VARIABLES ,Humans ,Genetic Predisposition to Disease ,Obesity ,GENOME-WIDE ASSOCIATION ,Biology ,Molecular epidemiology Aetiology, screening and detection [NCEBP 1] ,Aged ,Science & Technology ,Population Biology ,business.industry ,CARDIOVASCULAR-DISEASE RISK ,ta3121 ,Mendelian Randomization Analysis ,medicine.disease ,Vitamin D Deficiency ,BODY-MASS INDEX ,chemistry ,Genetic epidemiology ,3121 General medicine, internal medicine and other clinical medicine ,Multivariate Analysis ,North America ,Genetic Polymorphism ,Linear Models ,business ,Body mass index ,Population Genetics ,Biomarkers - Abstract
A mendelian randomization study based on data from multiple cohorts conducted by Karani Santhanakrishnan Vimaleswaran and colleagues re-examines the causal nature of the relationship between vitamin D levels and obesity., Background Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. Methods and Findings We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m2 higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10−27). The BMI allele score was associated both with BMI (p = 6.30×10−62) and 25(OH)D (−0.06% [95% CI −0.10 to −0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10−57 for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: −4.2 [95% CI −7.1 to −1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). Conclusions On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency. Please see later in the article for the Editors' Summary, Editors' Summary Background Obesity—having an unhealthy amount of body fat—is increasing worldwide. In the US, for example, a third of the adult population is now obese. Obesity is defined as having a body mass index (BMI, an indicator of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) of more than 30.0 kg/m2. Although there is a genetic contribution to obesity, people generally become obese by consuming food and drink that contains more energy than they need for their daily activities. Thus, obesity can be prevented by having a healthy diet and exercising regularly. Compared to people with a healthy weight, obese individuals have an increased risk of developing diabetes, heart disease and stroke, and tend to die younger. They also have a higher risk of vitamin D deficiency, another increasingly common public health concern. Vitamin D, which is essential for healthy bones as well as other functions, is made in the skin after exposure to sunlight but can also be obtained through the diet and through supplements. Why Was This Study Done? Observational studies cannot prove that obesity causes vitamin D deficiency because obese individuals may share other characteristics that reduce their circulating 25-hydroxy vitamin D [25(OH)D] levels (referred to as confounding). Moreover, observational studies cannot indicate whether the larger vitamin D storage capacity of obese individuals (vitamin D is stored in fatty tissues) lowers their 25(OH)D levels or whether 25(OH)D levels influence fat accumulation (reverse causation). If obesity causes vitamin D deficiency, monitoring and treating vitamin D deficiency might alleviate some of the adverse health effects of obesity. Conversely, if low vitamin D levels cause obesity, encouraging people to take vitamin D supplements might help to control the obesity epidemic. Here, the researchers use bi-directional “Mendelian randomization” to examine the direction and causality of the relationship between BMI and 25(OH)D. In Mendelian randomization, causality is inferred from associations between genetic variants that mimic the influence of a modifiable environmental exposure and the outcome of interest. Because gene variants do not change over time and are inherited randomly, they are not prone to confounding and are free from reverse causation. Thus, if a lower vitamin D status leads to obesity, genetic variants associated with lower 25(OH)D concentrations should be associated with higher BMI, and if obesity leads to a lower vitamin D status, then genetic variants associated with higher BMI should be associated with lower 25(OH)D concentrations. What Did the Researchers Do and Find? The researchers created a “BMI allele score” based on 12 BMI-related gene variants and two “25(OH)D allele scores,” which are based on gene variants that affect either 25(OH)D synthesis or breakdown. Using information on up to 42,024 participants from 21 studies, the researchers showed that the BMI allele score was associated with both BMI and with 25(OH)D levels among the study participants. Based on this information, they calculated that each 10% increase in BMI will lead to a 4.2% decrease in 25(OH)D concentrations. By contrast, although both 25(OH)D allele scores were strongly associated with 25(OH)D levels, neither score was associated with BMI. This lack of an association between 25(OH)D allele scores and obesity was confirmed using data from more than 100,000 individuals involved in 46 studies that has been collected by the GIANT (Genetic Investigation of Anthropometric Traits) consortium. What Do These Findings Mean? These findings suggest that a higher BMI leads to a lower vitamin D status whereas any effects of low vitamin D status on BMI are likely to be small. That is, these findings provide evidence for obesity as a causal factor in the development of vitamin D deficiency but not for vitamin D deficiency as a causal factor in the development of obesity. These findings suggest that population-level interventions to reduce obesity should lead to a reduction in the prevalence of vitamin D deficiency and highlight the importance of monitoring and treating vitamin D deficiency as a means of alleviating the adverse influences of obesity on health. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001383. The US Centers for Disease Control and Prevention provides information on all aspects of overweight and obesity (in English and Spanish); a data brief provides information about the vitamin D status of the US population The World Health Organization provides information on obesity (in several languages) The UK National Health Service Choices website provides detailed information about obesity and a link to a personal story about losing weight; it also provides information about vitamin D The International Obesity Taskforce provides information about the global obesity epidemic The US Department of Agriculture's ChooseMyPlate.gov website provides a personal healthy eating plan; the Weight-control Information Network is an information service provided for the general public and health professionals by the US National Institute of Diabetes and Digestive and Kidney Diseases (in English and Spanish) The US Office of Dietary Supplements provides information about vitamin D (in English and Spanish) MedlinePlus has links to further information about obesity and about vitamin D (in English and Spanish) Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) Overview and details of the collaborative large-scale genetic association study (D-CarDia) provide information about vitamin D and the risk of cardiovascular disease, diabetes and related traits
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- 2013
47. Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies
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Nettleton, J.A., McKeown, N.M., Kanoni, S., Lemaitre, R.N., Hivert, M.F., Ngwa, J., van Rooij, F.J., Sonestedt, E., Wojczynski, M.K., Ye, Z., Tanaka, T., Garcia, M., Anderson, J.S., Follis, J.L., Djousse, L., Mukamal, K., Papoutsakis, C., Mozaffarian, D., Zillikens, M.C., Bandinelli, S., Bennett, A.J., Borecki, I.B., Feitosa, M.F., Ferrucci, L., Forouhi, N.G., Groves, C.J., Hallmans, G., Harris, T., Hofman, A., Houston, D.K., Hu, F.B., Johansson, I., Kritchevsky, S.B., Langenberg, C., Launer, L., Liu, Y., Loos, R.J., Nalls, M., Orho-Melander, M., Renstrom, F., Rice, K., Riserus, U., Rolandsson, O., Rotter, J.I., Saylor, G., Sijbrands, E.J., Sjogren, P., Smith, A., Steingrímsdóttir, L., Uitterlinden, A.G., Wareham, N.J., Prokopenko, I., Pankow, J.S., van Duijn, C.M., Florez, J.C., Witteman, J.C., Dupuis, J., Dedoussis, G.V., Ordovas, J.M., Ingelsson, E., Cupples, L., Siscovick, D.S., Franks, P.W., Meigs, J.B., MAGIC Investigators, Dupuis, J., Claudia, L., Prokopenko, I., Saxena, R., Soranzo, N., Jackson, A.U., Wheeler, E., Glazer, N.L., Bouatia-Naji, N., Lindgren, C.M., Mägi, R., Morris, A.P., Randal, J., Rybin, D., Johnson, T., Henneman, P., Gieger, C., Thorleifsson, G., Steinthorsdottir, V., Dehghan, A., Hottenga, J.J., Franklin, C.S., Navarro, P., Song, K., Goe, A., Perry, J.R., Lajunen, T., Grallert, H., Li, M., Stringham, H.M., Kumari, M., Timpson, N.J., Shrader, P., Ingelsson, E., Zabena, C., O'Connell, J., Cavalcanti-Proença, C., Luan, J., Elliott, A., McCarroll, S.A., Payne, F., Roccasecca, R.M., Sethupathy, P., Andrew, T., Ariyurek, Y., Balkau, B., Barter, P., Bennett, A.J., Ben-Shlomo, Y., Bergmann, S., Bochud, M., Boerwinkle, E., Bonnefond, A., Bonnycastle, L.L., Böttcher, Y., Brunner, E., Bumpstead, S.J., Chen, Y.D., Chines, P., Clarke, R., Coin, L.J., Crawford, G.J., Crisponi, L., Day, I.N., Geus, Ed, Dina, C., Doney, A., Egan, J.M., Elliott, P., Erdos, M.R., Fischer-Rosinsky, A., Forouhi, N.G., Fox, C.S., Frants, R., Franzosi, M.G., Galan, P., Goodarzi, M.O., Graessler, J., Groves, C.J., Grundy, S., Gwilliam, R., Hallmans, G., Hammond, N., Han, X., Hartikainen, A.L., Hayward, C., Heath, S.C., Hercberg, S., Herder, C., Hicks, A.A., Hingorani, A.D., Hofman, A., Isomaa, B., Jula, A., Kaakinen, M., Kanoni, S., Kesaniemi, Y.A., Kivimaki, M., Knight, B., Koskinen, S., Kovacs, P., Lathrop, G.M., Lawlor, D.A., Li, Y., Lyssenko, V., Mahley, R., Mangino, M., Manning, A.K., Martínez-Larrad, M.T., McAteer, J.B., McPherson, R., Meisinger, C., Melzer, D., Meyre, D., Mitchell, B.D., Morken, M.A., Naitza, S., Narisu, N., Neville, M.J., Oostra, B.A., Orrù, M., Pakyz, R., Palmer, C.N., Paolisso, G., Pattaro, C., Pearson, D., Peden, J.F., Perola, M., Pfeiffer, A.F., Pichler, I., Polasek, O., Posthuma, D., Potter, S.C., Pouta, A., Psaty, B.M., Rathmann, W., Rayner, N.W., Rice, K., Ripatti, S., Rivadeneira, F., Rolandsson, O., Sandhu, M., Sanna, S., Sayer, A.A., Scheet, P., Scott, L.J., Seedorf, U., Sharp, S.J., Shields, B., Sijbrands, E.J., Silveira, A., Singleton, A., Smith, N.L., Sovio, U., Swift, A., Syddall, H., Syvänen, A.C., Tanaka, T., Tönjes, A., Tuomi, T., Uitterlinden, A.G., van Dijk, K.W., Varma, D., Visvikis-Siest, S., Vitart, V., Vogelzangs, N., Waeber, G., Wagner, P.J., Watkins, H., Weedon, M.N., Wild, S.H., Willemsen, G., Witteman, J.C., Yarnell, J.W., Zelenika, D., Zethelius, B., Zhai, G., Zhao, J.H., Zillikens, M.C., GIANT Consortium, X., Global BPgen Consortium, X., Loos, R.J., Meneton, P., Nathan, D.M., Williams, G.H., Hattersley, A.T., Silander, K., Salomaa, V., Smith, G.D., Bornstein, S.R., Schwarz, P., Spranger, J., Karpe, F., Shuldiner, A.R., Cooper, C., Dedoussis, G.V., Serrano-Ríos, M., Morris, A.D., Lind, L., Franks, P.W., Ebrahim, S., Marmot, M., Kuusisto, J., Laakso, M., Kao, W.H., Pankow, J.S., Pramstaller, P.P., Wichmann, H.E., Illig, T., Rudan, I., Wright, A., Stumvoll, M., Campbell, H., Wilson, J.F., Hamsten, A., Bergman, R.N., Buchanan, T.A., Collins, F.S., Mohlke, K.L., Tuomilehto, J., Valle, T.T., Altshuler, D., Rotter, J.I., Siscovick, D.S., Penninx, B.W., Boomsma, D., Deloukas, P., Spector, T.D., Frayling, T.M., Ferrucci, L., Kong, A., Thorsteinsdottir, U., Stefansson, K., van Duijn, C.M., Aulchenko, Y.S., Cao, A., Scuteri, A., Schlessinger, D., Uda, M., Ruokonen, A., Jarvelin, M.R., Waterworth, D.M., Vollenweider, P., Peltonen, L., Mooser, V., Abecasis, G.R., Wareham, N.J., Sladek, R., Froguel, P., Watanabe, R.M., Meigs, J.B., Groop, L., Boehnke, M., McCarthy, M.I., Florez, J.C., and Barroso, I.
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Adult ,Blood Glucose ,Male ,Genotype ,Reviews/Commentaries/ADA Statements ,Fasting ,Middle Aged ,Polymorphism, Single Nucleotide ,White People ,Genetic Loci ,Humans ,Insulin ,Female ,Aged ,Blood Glucose/genetics ,Blood Glucose/metabolism ,Edible Grain ,European Continental Ancestry Group ,Fasting/blood ,Genetic Loci/genetics ,Genome-Wide Association Study ,Insulin/blood ,Insulin/genetics ,Polymorphism, Single Nucleotide/genetics ,Meta-Analysis - Abstract
OBJECTIVE Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. RESEARCH DESIGN AND METHODS Via meta-analysis of data from 14 cohorts comprising ∼48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value
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- 2010
48. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche
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Jing Hua Zhao, Vilmundur Gudnason, Robin Haring, Enda M. Byrne, Christian Gieger, Marek Zygmunt, Lude Franke, Peter Kraft, Eric Boerwinkle, Matthias W. Beckmann, Catharina A. Hartman, Thorkild I. A. Sørensen, Aida Karina Dieffenbach, André G. Uitterlinden, Grant W. Montgomery, Graham G. Giles, Felix R. Day, Anja Rudolph, Arto Mannermaa, Sven Bergmann, Nora Franceschini, Julian Peto, Ellen W. Demerath, Diana L. Cousminer, Wei Ang, Gudmar Thorleifsson, Patrick F. McArdle, Dieter Flesch-Janys, Albertine J. Oldehinkel, Irene L. Andrulis, Aarno Palotie, Nicholas J. Timpson, Paolo Peterlongo, Johan G. Eriksson, Bernardo Bonanni, Dorret I. Boomsma, J. Margriet Collée, Immaculata De Vivo, Bjarke Feenstra, Teresa Ferreira, Cornelia M. van Duijn, Nancy L. Pedersen, Deborah J. Thompson, Peter Vollenweider, Douglas F. Easton, Pascal Guénel, Anna Maria Storniolo, Erik Ingelsson, Gisli Masson, Annika Lindblom, Stefania Bandinelli, Elisabeth Widen, Doris Stöckl, Veikko Salomaa, Zoltán Kutalik, Nicholas J. Wareham, Joanne M. Murabito, Eleonora Porcu, Fergus J. Couch, Katri Pylkäs, Luigi Ferrucci, Wendy L. McArdle, Frank Geller, Andrea D. Coviello, Lynda M. Rose, Daniel L. Koller, Ute Hamann, Ulla Sovio, Daniel F. Gudbjartsson, Georgia Chenevix-Trench, Roger L. Milne, Unnur Thorsteinsdottir, Paul M. Ridker, Henry Völzke, John R. B. Perry, Stephen J. Chanock, Tanguy Corre, Mads Melbye, Ben A. Oostra, Albert V. Smith, Tõnu Esko, Melissa E. Garcia, Debbie A Lawlor, Meir J. Stampfer, Per Hall, Patrick Sulem, Massimo Mangino, Nicholas G. Martin, David J. Hunter, Laura Crisponi, Tatiana Foroud, Antonietta Robino, Michael J. Econs, Susan M. Ring, Natalia Tšernikova, Dirkje S. Postma, Lavinia Paternoster, Peter A. Fasching, Tamara B. Harris, Ellen A. Nohr, Javier Benitez, Ruth J. F. Loos, Robert Winqvist, Andres Metspalu, Jenny A. Visser, Heather A. Boyd, Jonathan Tyrer, Alexander Teumer, Tim D. Spector, Sandra Lai, Douglas P. Kiel, Kamila Czene, Hiltrud Brauch, George Davey Smith, Julia A. Knight, Erin K. Wagner, Suiqun Guo, Tune H. Pers, Patrik K. E. Magnusson, Kathryn L. Lunetta, Hoda Anton-Culver, Marjanka K. Schmidt, George McMahon, Ken K. Ong, Adamo Pio D'Adamo, Veli-Matti Kosma, Jinhui Chen, Paul D.P. Pharoah, Diether Lambrechts, Femke Atsma, Serena Sanna, Ilja M. Nolte, Eco de Geus, Daniel I. Chasman, Emmi Tikkanen, John L. Hopper, Anna Murray, Laura M. Yerges-Armstrong, Sanela Kjellqvist, Eva Albrecht, Hermann Brenner, Paolo Gasparini, Bruce H. R. Wolffenbuttel, Alison M. Dunning, John P. Rice, Craig E. Pennell, Mark I. McCarthy, Andrea Ganna, Henri Wallaschofski, Frank B. Hu, Gérard Waeber, Henrik Flyger, Evelin Mihailov, Peter Devilee, Lisette Stolk, Behrooz Z. Alizadeh, Jouke-Jan Hottenga, Najaf Amin, Patrick Neven, Reedik Mägi, Kyriaki Michailidou, Kari Stefansson, Munro Peacock, Julie E. Buring, Laura J. Bierut, Cathy E. Elks, Marjo-Riitta Järvelin, Montserrat Garcia-Closas, Anneli Pouta, David Schlessinger, Harold Snieder, Chunyan He, Joe Dennis, Heli Nevanlinna, Gonneke Willemsen, Andrew C. Heath, Elizabeth A. Streeten, Albert Hofman, Angela Cox, Maartje J. Hooning, Lili Milani, Margaret J. Wright, Fernando Rivadeneira, Gudny Eiriksdottir, Mellissa C. Southey, Qin Wang, Paolo Radice, Manjeet K. Bolla, Kay-Tee Khaw, Carl Blomqvist, Melanie Waldenberger, Sheila Ulivi, David Couper, Jenny Chang-Claude, David Karasik, Stig E. Bojesen, Andrew D. Johnson, David P. Strachan, Perry, John [0000-0001-6483-3771], Day, Felix [0000-0003-3789-7651], Thompson, Deborah [0000-0003-1465-5799], Zhao, Jing Hua [0000-0003-4930-3582], Dennis, Joe [0000-0003-4591-1214], Dunning, Alison [0000-0001-6651-7166], Pharoah, Paul [0000-0001-8494-732X], Sovio, Ulla [0000-0002-0799-1105], Tyrer, Jonathan [0000-0003-3724-4757], Wang, Jean [0000-0002-9139-0627], Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Easton, Douglas [0000-0003-2444-3247], Ong, Kenneth [0000-0003-4689-7530], Apollo - University of Cambridge Repository, Australian Ovarian Cancer Study, GENICA Network, kConFab, LifeLines Cohort Study, InterAct Consortium, Early Growth Genetics (EGG) Consortium, Cousminer, D.L., Stergiakouli, E., Berry, D.J., Ang, W., Groen-Blokhuis, M.M., Körner, A., Siitonen, N., Ntalla, I., Marinelli, M., Perry, J.R., Kettunen, J., Jansen, R., Surakka, I., Timpson, N.J., Ring, S., McMahon, G., Power, C., Wang, C., Kähönen, M., Viikari, J., Lehtimäki, T., Middeldorp, C.M., Hulshoff Pol, H.E., Neef, M., Weise, S., Pahkala, K., Niinikoski, H., Zeggini, E., Panoutsopoulou, K., Bustamante, M., Penninx, B.W., Murabito, J., Torrent, M., Dedoussis, G.V., Kiess, W., Boomsma, D.I., Pennell, C.E., Raitakari, O.T., Hyppönen, E., Davey Smith, G., Ripatti, S., McCarthy, M.I., Widén, E., Alizadeh, B.Z., de Boer, R.A., Boezen, H.M., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, H.L., van der Klauw, M.M., Navis, G., Ormel, J., Postma, D., Rosmalen, J.G., Slaets, J.P., Snieder, H., Stolk, R.P., Wolffenbuttel, B.H., Wijmenga, C., Forouhi, N., Kerrison, N.D., Langenberg, C., Scott, R.A., Sharp, S.J., Sims, M., Barroso, I., Deloukas, P., Arriola, L., Balkau, B., Barricarte, A., Boeing, H., Franks, P.W., Gonzalez, C., Grioni, S., Kaaks, R., Key, T.J., Navarro, C., Nilsson, P.M., Overvad, K., Palli, D., Panico, S., Quirós, J., Rolandsson, O., Sacerdote, C., Sánchez, M.J., Slimani, N., Tjonneland, A., Tumino, R., van der A, D.L., van der Schouw, Y.T., Riboli, E., Wareham, N.J., Bowtell, D.D., Green, A., Chenevix-Trench, G., deFazio, A., Gertig, D., Webb, P.M., Brauch, H., Justenhoven, C., Hamann, U., Ko, Y.D., Baisch, C., Fischer, H.P., Pesch, B., Rabstein, S., Spickenheuer, A., Harth, V., Aghmesheh, M., Amor, D., Andrews, L., Antill, Y., Armitage, S., Arnold, L., Balleine, R., Bankier, A., Bastick, P., Beesley, J., Beilby, J., Bennett, I., Bennett, B., Berry, G., Blackburn, A., Bogwitz, M., Brennan, M., Brown, M., Buckley, M., Burgess, M., Burke, J., Butow, P., Byron, K., Callen, D., Campbell, I., Chauhan, D., Christian, A., Clarke, C., Colley, A., Cotton, D., Crook, A., Cui, J., Culling, B., Cummings, M., Dawson, S.J., Delatycki, M., Dickson, R., Dixon, J., Dobrovic, A., Dudding, T., Edkins, T., Edwards, S., Eisenbruch, M., Farshid, G., Fawcett, S., Fellows, A., Fenton, G., Field, M., Firgaira, F., Flanagan, J., Fleming, J., Fong, P., Forbes, J., Fox, S., French, J., Friedlander, M., Gaff, C., Gardner, M., Gattas, M., George, P., Giles, G., Gill, G., Goldblatt, J., Greening, S., Grist, S., Eric, H., Hardie, K., Harris, M., Hart, S., Hayward, N., Healey, S., Heiniger, L., Hopper, J., Humphrey, E., Hunt, C., James, P., Jenkins, M., Jones, A., Kefford, R., Kidd, A., Kiely, B., Kirk, J., Koehler, J., Kollias, J., Kovalenko, S., Lakhani, S., Leaming, A., Leary, J., Lim, J., Lindeman, G., Lipton, L., Lobb, L., Mann, G., Marsh, D., McLachlan, S.A., Meiser, B., Meldrum, C., Milne, R., Mitchell, G., Newman, B., O'Connell, S., O'Loughlin, I., Osborne, R., Pachter, N., Patterson, B., Peters, L., Phillips, K., Price, M., Purser, L., Reeve, J., Reeve, T., Richards, R., Rickard, E., Robinson, B., Rudzki, B., Saleh, M., Salisbury, E., Sambrook, J., Saunders, C., Saunus, J., Sayer, R., Scott, E., Scott, R., Scott, C., Seshadri, R., Sexton, A., Sharma, R., Shelling, A., Simpson, P., Southey, M., Spurdle, A., Suthers, G., Sykes, P., Taylor, D., Taylor, J., Thierry, B., Thompson, E., Thorne, H., Townshend, S., Trainer, A., Tran, L., Tucker, K., Tyler, J., Visvader, J., Walker, L., Walpole, I., Waring, P., Warner, B., Warren, G., Williams, R., Wilson, J., Winship, I., Wu, K., Young, M.A., Public Health, Internal Medicine, Epidemiology, Clinical Genetics, Medical Oncology, Child and Adolescent Psychiatry / Psychology, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Groningen Research Institute for Asthma and COPD (GRIAC), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Political Science, Perry, John R. B, Day, Felix, Elks, Cathy E, Sulem, Patrick, Thompson, Deborah J, Ferreira, Teresa, He, Chunyan, Chasman, Daniel I, Esko, Tõnu, Thorleifsson, Gudmar, Albrecht, Eva, Ang, Wei Q, Corre, Tanguy, Cousminer, Diana L, Feenstra, Bjarke, Franceschini, Nora, Ganna, Andrea, Johnson, Andrew D, Kjellqvist, Sanela, Lunetta, Kathryn L, Mcmahon, George, Nolte, Ilja M, Paternoster, Lavinia, Porcu, Eleonora, Smith, Albert V, Stolk, Lisette, Teumer, Alexander, Tšernikova, Natalia, Tikkanen, Emmi, Ulivi, Sheila, Wagner, Erin K, Amin, Najaf, Bierut, Laura J, Byrne, Enda M, Hottenga, Jouke Jan, Koller, Daniel L, Mangino, Massimo, Pers, Tune H, Yerges Armstrong, Laura M, Hua Zhao, Jing, Andrulis, Irene L, Anton Culver, Hoda, Atsma, Femke, Bandinelli, Stefania, Beckmann, Matthias W, Benitez, Javier, Blomqvist, Carl, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Brauch, Hiltrud, Brenner, Hermann, Buring, Julie E, Chang Claude, Jenny, Chanock, Stephen, Chen, Jinhui, Chenevix Trench, Georgia, Collée, J. Margriet, Couch, Fergus J, Couper, David, Coviello, Andrea D, Cox, Angela, Czene, Kamila, D'Adamo, Adamo Pio, Davey Smith, George, De Vivo, Immaculata, Demerath, Ellen W, Dennis, Joe, Devilee, Peter, Dieffenbach, Aida K, Dunning, Alison M, Eiriksdottir, Gudny, Eriksson, Johan G, Fasching, Peter A, Ferrucci, Luigi, Flesch Janys, Dieter, Flyger, Henrik, Foroud, Tatiana, Franke, Lude, Garcia, Melissa E, García Closas, Montserrat, Geller, Frank, de Geus, Eco E. J, Giles, Graham G, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Guénel, Pascal, Guo, Suiqun, Hall, Per, Hamann, Ute, Haring, Robin, Hartman, Catharina A, Heath, Andrew C, Hofman, Albert, Hooning, Maartje J, Hopper, John L, Hu, Frank B, Hunter, David J, Karasik, David, Kiel, Douglas P, Knight, Julia A, Kosma, Veli Matti, Kutalik, Zoltan, Lai, Sandra, Lambrechts, Diether, Lindblom, Annika, Mägi, Reedik, Magnusson, Patrik K, Mannermaa, Arto, Martin, Nicholas G, Masson, Gisli, Mcardle, Patrick F, Mcardle, Wendy L, Melbye, Mad, Michailidou, Kyriaki, Mihailov, Evelin, Milani, Lili, Milne, Roger L, Nevanlinna, Heli, Neven, Patrick, Nohr, Ellen A, Oldehinkel, Albertine J, Oostra, Ben A, Palotie, Aarno, Peacock, Munro, Pedersen, Nancy L, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P, Postma, Dirkje S, Pouta, Anneli, Pylkäs, Katri, Radice, Paolo, Ring, Susan, Rivadeneira, Fernando, Robino, Antonietta, Rose, Lynda M, Rudolph, Anja, Salomaa, Veikko, Sanna, Serena, Schlessinger, David, Schmidt, Marjanka K, Southey, Mellissa C, Sovio, Ulla, Stampfer, Meir J, Stöckl, Dori, Storniolo, Anna M, Timpson, Nicholas J, Tyrer, Jonathan, Visser, Jenny A, Vollenweider, Peter, Völzke, Henry, Waeber, Gerard, Waldenberger, Melanie, Wallaschofski, Henri, Wang, Qin, Willemsen, Gonneke, Winqvist, Robert, Wolffenbuttel, Bruce H. R, Wright, Margaret J, Boomsma, Dorret I, Econs, Michael J, Khaw, Kay Tee, Loos, Ruth J. F, Mccarthy, Mark I, Montgomery, Grant W, Rice, John P, Streeten, Elizabeth A, Thorsteinsdottir, Unnur, van Duijn, Cornelia M, Alizadeh, Behrooz Z, Bergmann, Sven, Boerwinkle, Eric, Boyd, Heather A, Crisponi, Laura, Gasparini, Paolo, Gieger, Christian, Harris, Tamara B, Ingelsson, Erik, Järvelin, Marjo Riitta, Kraft, Peter, Lawlor, Debbie, Metspalu, Andre, Pennell, Craig E, Ridker, Paul M, Snieder, Harold, Sørensen, Thorkild I. A, Spector, Tim D, Strachan, David P, Uitterlinden, André G, Wareham, Nicholas J, Widen, Elisabeth, Zygmunt, Marek, Murray, Anna, Easton, Douglas F, Stefansson, Kari, Murabito, Joanne M, Ong, Ken K., Panico, Salvatore, Perry, John R. B., Elks, Cathy E., Thompson, Deborah J., Chasman, Daniel I., Ang, Wei Q., Cousminer, Diana L., Johnson, Andrew D., Lunetta, Kathryn L., Nolte, Ilja M., Smith, Albert V., Wagner, Erin K., Bierut, Laura J., Byrne, Enda M., Koller, Daniel L., Pers, Tune H., Yerges Armstrong, Laura M., Zhao, Jing Hua, Andrulis, Irene L., Beckmann, Matthias W., Bojesen, Stig E., Bolla, Manjeet K., Buring, Julie E., Couch, Fergus J., Coviello, Andrea D., D'Adamo, ADAMO PIO, Smith, George Davey, Demerath, Ellen W., Dieffenbach, Aida K., Dunning, Alison M., Eriksson, Johan G., Fasching, Peter A., Garcia, Melissa E., De Geus, Eco E. J., Giles, Graham G., Gudbjartsson, Daniel F., Hartman, Catharina A., Heath, Andrew C., Hooning, Maartje J., Hopper, John L., Hu, Frank B., Hunter, David J., Kiel, Douglas P., Knight, Julia A., Magnusson, Patrik K., Martin, Nicholas G., Mcardle, Patrick F., Mcardle, Wendy L., Milne, Roger L., Nohr, Ellen A., Oldehinkel, Albertine J., Oostra, Ben A., Pedersen, Nancy L., Pharoah, Paul D. P., Postma, Dirkje S., Rose, Lynda M., Schmidt, Marjanka K., Southey, Mellissa C., Stampfer, Meir J., Storniolo, Anna M., Timpson, Nicholas J., Visser, Jenny A., Wolffenbuttel, Bruce H. R., Wright, Margaret J., Boomsma, Dorret I., Econs, Michael J., Loos, Ruth J. F., Mccarthy, Mark I., Montgomery, Grant W., Rice, John P., Streeten, Elizabeth A., Van Duijn, Cornelia M., Alizadeh, Behrooz Z., Boyd, Heather A., Harris, Tamara B., Pennell, Craig E., Ridker, Paul M., Sørensen, Thorkild I. A., Spector, Tim D., Strachan, David P., Uitterlinden, André G., Wareham, Nicholas J., Easton, Douglas F., and Murabito, Joanne M.
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Netherlands Twin Register (NTR) ,Male ,Parents ,CENTRAL PRECOCIOUS PUBERTY ,Genome-wide association study ,Disease ,VARIANTS ,DISEASE ,Body Mass Index ,0302 clinical medicine ,Adolescent ,Age Factors ,Alleles ,Breast Neoplasms/genetics ,Cardiovascular Diseases/genetics ,Child ,Diabetes Mellitus, Type 2/genetics ,Europe/ethnology ,Female ,Genetic Loci/genetics ,Genome-Wide Association Study ,Genomic Imprinting/genetics ,Humans ,Hypothalamo-Hypophyseal System/physiology ,Intercellular Signaling Peptides and Proteins/genetics ,Membrane Proteins/genetics ,Menarche/genetics ,Obesity/genetics ,Ovary/physiology ,Polymorphism, Single Nucleotide/genetics ,Potassium Channels, Tandem Pore Domain/genetics ,Proteins/genetics ,Quantitative Trait Loci/genetics ,Receptors, GABA-B/metabolism ,Receptors, Retinoic Acid/metabolism ,Ribonucleoproteins/genetics ,Intercellular Signaling Peptides and Protein ,Age Factor ,Tandem Pore Domain ,GENE-EXPRESSION ,0303 health sciences ,BREAST-CANCER RISK ,3. Good health ,Ribonucleoproteins ,Cardiovascular Diseases ,Menarche ,Intercellular Signaling Peptides and Proteins ,Science & Technology - Other Topics ,GENICA Network ,Breast Neoplasm ,Type 2 ,Human ,Hypothalamo-Hypophyseal System ,Quantitative Trait Loci ,Article ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,REVEALS ,Diabetes Mellitus ,Polymorphism ,METAANALYSIS ,Science & Technology ,ta1184 ,Calcium-Binding Proteins ,Proteins ,HUMAN PREFRONTAL CORTEX ,ta3121 ,ta3123 ,Diabetes Mellitus, Type 2 ,Genetic Loci ,CELLS ,030217 neurology & neurosurgery ,LifeLines Cohort Study ,Potassium Channels ,Receptors, Retinoic Acid ,Retinoic Acid ,Australian Ovarian Cancer Study ,Polymorphism (computer science) ,Cardiovascular Disease ,Receptors ,WIDE ASSOCIATION ,Membrane Protein ,Allele ,2. Zero hunger ,Genetics ,Multidisciplinary ,Single Nucleotide ,Europe ,Multidisciplinary Sciences ,kConFab ,Breast Neoplasms ,Genomic Imprinting ,Membrane Proteins ,Obesity ,Ovary ,Polymorphism, Single Nucleotide ,Potassium Channels, Tandem Pore Domain ,Receptors, GABA-B ,General Science & Technology ,Ubiquitin-Protein Ligases ,Quantitative trait locus ,Biology ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,Early Growth Genetics (EGG) Consortium ,030304 developmental biology ,Protein ,GABA-B ,Ribonucleoprotein ,InterAct Consortium ,Genetic architecture ,Parent ,Genomic imprinting - Abstract
Contains fulltext : 136472.pdf (Publisher’s version ) (Closed access) Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.
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