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1. Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women

Author: Jones, G. (Garan), Trajanoska, K. (Katerina), Santanasto, A.J. (Adam J.), Stringa, N. (Najada), Kuo, C.-L. (Chia-Ling), Atkins, J.L. (Janice L.), Lewis, J.R. (Joshua), Duong, T.V. (ThuyVy), Hong, S. (Shengjun), Biggs, M.L. (M.), Luan, J. (Jian’an), Sarnowski, C., Lunetta, K.L. (Kathryn), Tanaka, T. (Toshiko), Wojczynski, M.K. (Mary ), Cvejkus, R. (Ryan), Nethander, M. (Maria), Ghasemi, S. (Sahar), Yang, J. (Jingyun), Zillikens, M.C. (Carola), Walter, S. (Stefan), Sicinski, K. (Kamil), Kague, E. (Erika), Ackert-Bicknell, C.L. (Cheryl L.), Arking, D.E. (Dan E.), Windham, B.G. (Gwen), Boerwinkle, E.A. (Eric), Grove, M.L. (Megan L.), Graff, M. (Misa), Spira, D. (Dominik), Demuth, I. (Ilja), Velde, N. (Nathalie) van der, de Groot, L.C.P.G.M. (Lisette C. P. G. M.), Psaty, B.M. (Bruce M.), Odden, M.C. (Michelle C.), Fohner, A.E. (Alison E.), Langenberg, C. (Claudia), Wareham, N.J. (Nick), Bandinelli, S. (Stefania), Schoor, N.M. (Natasja) van, Huisman, M. (Martijn), Tan, Q. (Qihua), Zmuda, J. (Joseph), Mellström, D. (Dan), Karlsson, M. (Magnus), Bennett, D.A. (David), Buchman, A.S. (Aron S.), De Jager, P., Uitterlinden, A.G. (Andre G.), Völker, U. (Uwe), Kocher, T. (Thomas), Teumer, A. (Alexander), Rodríguez-Mañas, L. (Leocadio), García, F.J. (Francisco J.), Carnicero, J.A. (José A.), Herd, P. (Pamela), Bertram, L. (Lars), Ohlsson, C. (Claes), Murabito, J. (Joanne), Melzer, D. (David), Kuchel, G.A. (George A.), Ferrucci, L. (Luigi), Karasik, D. (David), Rivadeneira Ramirez, F. (Fernando), Kiel, D.P. (Douglas P.), Pilling, L.C. (Luke C.), Jones, G. (Garan), Trajanoska, K. (Katerina), Santanasto, A.J. (Adam J.), Stringa, N. (Najada), Kuo, C.-L. (Chia-Ling), Atkins, J.L. (Janice L.), Lewis, J.R. (Joshua), Duong, T.V. (ThuyVy), Hong, S. (Shengjun), Biggs, M.L. (M.), Luan, J. (Jian’an), Sarnowski, C., Lunetta, K.L. (Kathryn), Tanaka, T. (Toshiko), Wojczynski, M.K. (Mary ), Cvejkus, R. (Ryan), Nethander, M. (Maria), Ghasemi, S. (Sahar), Yang, J. (Jingyun), Zillikens, M.C. (Carola), Walter, S. (Stefan), Sicinski, K. (Kamil), Kague, E. (Erika), Ackert-Bicknell, C.L. (Cheryl L.), Arking, D.E. (Dan E.), Windham, B.G. (Gwen), Boerwinkle, E.A. (Eric), Grove, M.L. (Megan L.), Graff, M. (Misa), Spira, D. (Dominik), Demuth, I. (Ilja), Velde, N. (Nathalie) van der, de Groot, L.C.P.G.M. (Lisette C. P. G. M.), Psaty, B.M. (Bruce M.), Odden, M.C. (Michelle C.), Fohner, A.E. (Alison E.), Langenberg, C. (Claudia), Wareham, N.J. (Nick), Bandinelli, S. (Stefania), Schoor, N.M. (Natasja) van, Huisman, M. (Martijn), Tan, Q. (Qihua), Zmuda, J. (Joseph), Mellström, D. (Dan), Karlsson, M. (Magnus), Bennett, D.A. (David), Buchman, A.S. (Aron S.), De Jager, P., Uitterlinden, A.G. (Andre G.), Völker, U. (Uwe), Kocher, T. (Thomas), Teumer, A. (Alexander), Rodríguez-Mañas, L. (Leocadio), García, F.J. (Francisco J.), Carnicero, J.A. (José A.), Herd, P. (Pamela), Bertram, L. (Lars), Ohlsson, C. (Claes), Murabito, J. (Joanne), Melzer, D. (David), Kuchel, G.A. (George A.), Ferrucci, L. (Luigi), Karasik, D. (David), Rivadeneira Ramirez, F. (Fernando), Kiel, D.P. (Douglas P.), and Pilling, L.C. (Luke C.)
Abstract: Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1p = 4 × 10−17), arthritis (GDF5p = 4 × 10−13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.
Published: 2021
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2. Genetic basis of falling risk susceptibility in the UK Biobank Study

Author: 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
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3. Genetics of Bone and Muscle Interactions in Humans

Author: Trajanoska, K., Rivadeneira Ramirez, F. (Fernando), Kiel, D.P. (Douglas), Karasik, D. (David), Trajanoska, K., Rivadeneira Ramirez, F. (Fernando), Kiel, D.P. (Douglas), and Karasik, D. (David)
Abstract: Purpose of Review To summarize the evidence from recent studies on the shared genetics between bone and muscle in humans. Recent Findings Genome-wide association studies (GWAS) have successfully identified a multitude of loci influencing the variability of different bone or muscle parameters, with multiple loci overlapping between the traits. In addition, joint analyses of multiple correlated musculoskeletal traits (i.e., multivariate GWAS) have underscored several genes with possible pleiotropic effects on both bone and muscle including MEF2C and SREBF1. Notably, several of the proposed pleiotropic genes have been validated using human cells or animal models. Summary It is clear that the study of pleiotropy may provide novel insights into disease pathophysiology potentially leading to the identification of new treatment strategies that simultaneously prevent or treat both osteoporosis and sarcopenia. However, the role of muscle factors (myokines) that stimulate bone metabolism, as well as osteokines that affect muscles, is in its earliest stage of understanding
Published: 2019
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4. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

Author: Jiang, X. (Xia), O'Reilly, P. F. (Paul F.), Aschard, H. (Hugues), Hsu, Y.-H. (Yi-Hsiang), Richards, J. B. (J. Brent), Dupuis, J. (Josee), Ingelsson, E. (Erik), Karasik, D. (David), Pilz, S. (Stefan), Berry, D. (Diane), Kestenbaum, B. (Bryan), Zheng, J. (Jusheng), Luan, J. (Jianan), Sofianopoulou, E. (Eleni), Streeten, E. A. (Elizabeth A.), Albanes, D. (Demetrius), Lutsey, P. L. (Pamela L.), Yao, L. (Lu), Tang, W. (Weihong), Econs, M. J. (Michael J.), Wallaschofski, H. (Henri), Voelzke, H. (Henry), Zhou, A. (Ang), Power, C. (Chris), McCarthy, M. I. (Mark I.), Michos, E. D. (Erin D.), Boerwinkle, E. (Eric), Weinstein, S. J. (Stephanie J.), Freedman, N. D. (Neal D.), Huang, W.-Y. (Wen-Yi), Van Schoor, N. M. (Natasja M.), van der Velde, N. (Nathalie), de Groot, L. C. (Lisette C. P. G. M.), Enneman, A. (Anke), Cupples, L. A. (L. Adrienne), Booth, S. L. (Sarah L.), Vasan, R. S. (Ramachandran S.), Liu, C.-T. (Ching-Ti), Zhou, Y. (Yanhua), Ripatti, S. (Samuli), Ohlsson, C. (Claes), Vandenput, L. (Liesbeth), Lorentzon, M. (Mattias), Eriksson, J. G. (Johan G.), Shea, M. K. (M. Kyla), Houston, D. K. (Denise K.), Kritchevsky, S. B. (Stephen B.), Liu, Y. (Yongmei), Lohman, K. K. (Kurt K.), Ferrucci, L. (Luigi), Peacock, M. (Munro), Gieger, C. (Christian), Beekman, M. (Marian), Slagboom, E. (Eline), Deelen, J. (Joris), van Heemst, D. (Diana), Kleber, M. E. (Marcus E.), Maerz, W. (Winfried), de Boer, I. H. (Ian H.), Wood, A. C. (Alexis C.), Rotter, J. I. (Jerome I.), Rich, S. S. (Stephen S.), Robinson-Cohen, C. (Cassianne), den Heijer, M. (Martin), Järvelin, M.-R. (Marjo-Riitta), Cavadino, A. (Alana), Joshi, P. K. (Peter K.), Wilson, J. F. (James F.), Hayward, C. (Caroline), Lind, L. (Lars), Michaelsson, K. (Karl), Trompet, S. (Stella), Zillikens, M. C. (M. Carola), Uitterlinden, A. G. (Andre G.), Rivadeneira, F. (Fernando), Broer, L. (Linda), Zgaga, L. (Lina), Campbell, H. (Harry), Theodoratou, E. (Evropi), Farrington, S. M. (Susan M.), Timofeeva, M. (Maria), Dunlop, M. G. (Malcolm G.), Valdes, A. M. (Ana M.), Tikkanen, E. (Emmi), Lehtimaki, T. (Terho), Lyytikainen, L.-P. (Leo-Pekka), Kahonen, M. (Mika), Raitakari, O. T. (Olli T.), Mikkila, V. (Vera), Ikram, M. A. (M. Arfan), Sattar, N. (Naveed), Jukema, J. W. (J. Wouter), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Forouhi, N. G. (Nita G.), Gundersen, T. E. (Thomas E.), Khaw, K.-T. (Kay-Tee), Butterworth, A. S. (Adam S.), Danesh, J. (John), Spector, T. (Timothy), Wang, T. J. (Thomas J.), Hypponen, E. (Elina), Kraft, P. (Peter), and Kiel, D. P. (Douglas P.)
Subjects: Risk factors, Epidemiology, Genetics research, Genome-wide association studies
Abstract: Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10−9 at rs8018720 in SEC23A, and P = 1.9×10−14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene–gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
Published: 2018

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

Author: Hinney, A. (Anke), Kesselmeier, M. (M.), Jall, S. (S.), Volckmar, A.-L. (A. L.), Föcker, M. (M.), Antel, J. (J.), Heid, I.M. (Iris), Winkler, T.W. (Thomas W.), Grant, S.F.A. (S. F.A.), Guo, Y. (Yongli), Bergen, A.W. (Andrew), Grant, S.F.A. (Struan), Berrettini, W. (Wade), Hakonarson, H. (Hakon), Herpertz-Dahlmann, B. (B.), De Zwaan, M. (M.), Herzog, W. (W.), Ehrlich, S.M. (Stefan), Zipfel, S. (S.), Egberts, K. (Karin), Adan, R. (R.), Brandys, M. (M.), Elburg, A.A. (Annemarie) van, Boraska Perica, V. (V.), Müller, T.D., Tschöp, M.H. (M. H.), Zeggini, E. (Eleftheria), Bulik, C.M. (C. M.), Collier, D.A. (David), Scherag, A. (A.), Hebebrand, J. (J.), Tschop, M. (Matthias), Floyd, J. (Jamie), Thornton, L.M. (Laura), Huckins, L.M. (Laura M), Southam, L. (Lorraine), Rayner, N.W. (Nigel William), Tachmazidou, I. (Ioanna), Klump, K.L. (K. L.), Treasure, J. (Janet), Lewis, C.M. (Cathryn), Schmidt, U. (Ulrike), Tozzi, F. (Federica), Iezebrink, K. (Kirsty), Gorwood, P. (Philip), Kas, M.J.H. (Martien), Favaro, A. (Angela), Santonastaso, P. (Paolo), Fernández-Aranda, F. (Fernando), Gratacos, M. (Monica), Rybakowski, F. (Filip), Dmitrzak-Weglarz, M. (Monika), Kaprio, J. (Jaakko), Keski-Rahkonen, A. (Anna), Raevuori-Helkamaa, A. (Anu), Furth, E.F. (Eric) van, Slof-Op’t Landt, M.C.T. (Margarita C. T.), Hudson, J.I. (James I), Knudsen, G.P.S. (Gun Peggy S.), Monteleone, P. (Palmiero), Kaplan, A.S. (Allan S), Karwautz, A. (Andreas), Li, D. (Dong), Komaki, G. (Gen), Ando, T. (Tetsuya), Inoko, H. (Hidetoshi), Esko, T. (T.), Fischer, K. (Krista), Männik, K. (Katrin), Metspalu, A. (Andres), Baker, J.H. (Jessica H), Cone, R.D. (Roger D), Esko, T. (Tõnu), DeSocio, J.E. (Janiece E), Hilliard, C.E. (Christopher E), O’Toole, J.K. (Julie K), Pantel, J. (Jacques), Szatkiewicz, J.P. (Jin P), Taico, C. (Chrysecolla), Zerwas, S. (Stephanie), Trace, S.E. (Sara E), Davis, O.S.P. (Oliver S.), Helder, S. (Sietske), Bühren, K. (Katharina), Burghardt, R. (Roland), Imgart, H. (Hartmut), Scherag, A. (Andre), Boni, C. (Claudette), Ramoz, N. (Nicolas), Versini, A. (Audrey), Danner, U.N. (Unna N), de Kove, C. (Carolien), Hendriks, J. (Judith), Koeleman, B.P.C. (Bobby P. C.), Ophoff, R.A. (Roel), Strengman, E. (Eric), Bruson, A. (Alice), Clementi, M. (Maurizio), Degortes, D. (Daniela), Forzan, M. (Monica), Tenconi, E. (Elena), Docampo, E. (Elisa), Jiménez-Murcia, G.E.S. (Geòrgia Escaramí Susana), Lissowska, J. (Jolanta), Rajewski, A. (Andrzej), Szeszenia-Dabrowska, N. (Neonila), Slopien, A. (Agnieszka), Hauser, J. (J.), Karhunen, L. (Leila), Meulenbelt, I. (Ingrid), Slagboom, P.E. (Eline), Tortorella, A. (Alfonso), Maj, M. (Mario), Dedoussis, G.V. (George), Dedoussis, G.V. (G. V.), Koeleman, B.P.C. (Bobby), Gonidakis, F. (Fragiskos), Tziouvas, K. (Konstantinos), Tsitsika, A. (Artemis), Papezova, H. (Hana), Slachtova, L. (Lenka), Martaskova, D. (Debora), Kennedy, J.L., Levitan, R.D. (Robert D), Yilmaz, Z. (Zeynep), Huemer, J. (Julia), Koubek, D. (Doris), Merl, E. (Elisabeth), Wagner, G. (Gudrun), Lichtenstein, P. (Paul), Breen, G. (Gerome), Cohen-Woods, S. (Sarah), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Cichon, S. (Sven), Giegling, I. (Ina), Herms, S. (Stefan), Rujescu, D. (Dan), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Sladek, R. (Rob), Gambaro, G. (Giovanni), Soranzo, N. (Nicole), Julia, A. (Antonio), Marsal, S. (Sara), Rabionet, R. (Raquel), Gaborieau, V. (Valerie), Dick, D.M. (Danielle), Palotie, A. (A.), Ripatti, S. (Samuli), Widen, E., Espeseth, T. (Thomas), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Steen, V.M. (Vidar), Le Hellard, S. (Stephanie), Mattingsdal, M. (Morten), Ntalla, I. (Ioanna), Bencko, V. (Vladimir), Foretova, L. (Lenka), Janout, V. (Vladimir), Navratilova, M. (Marie), Pinto, D. (Dalila), Scherer, S.W. (Stephen W), Carlberg, L. (Laura), Schosser, A. (Alexandra), Alfredsson, L. (Lars), Pinto, D. (Duane), Scherer, S.W. (Stephen), Padyukov, L. (Leonid), Finan, C. (Chris), Kalsi, G. (Gursharan), Roberts, M. (Marion), Logan, D.W. (Darren W), Peltonen, L. (Leena Johanna), Ritchie, G.R.S. (Graham R.S.), Barrett, J.C. (Jeffrey), Estivill, X. (Xavier), Sullivan, P.F. (Patrick), Anderson, C.A. (Carl A), McGinnis, R. (Ralph), Sambrook, J. (Jennifer), Stephens, J. (Jonathan), Ouwehand, W.H. (Willem), McArdle, P.F. (P. F.), Ring, S.M. (Susan), Strachan, D.P. (David), Alexander, G. (Graeme), Conlon, P.J. (Peter J), Dominiczak, A. (Anna), Duncanson, A. (Audrey), Padyukov, L. (L.), Langford, C. (Cordelia), Lord, G. (Graham), Conlon, P. (Peter), Sandford, R. (Richard), Sheerin, N. (Neil), Vannberg, F.O. (Frederik O), Blackburn, H. (Hannah), Maxwell, A.P. (A.), Edkins, T. (Ted), Gillman, M.W. (Matthew W.), Gray, E. (Emma), Hunt, S.E. (Sarah E), Nengut, S.-G. (Suna-Gumuscu), Potter, S.C. (Simon), Rich, S.S. (Stephen), Simpkin, D. (Douglas), Whittaker, P. (Pamela), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N. (N.), Benke, K. (K.), Berry, D. (Diane), Boomsma, D.I. (Dorret), Bradfield, J.P. (Jonathan), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cooper, C. (C.), Cousminer, D.L. (Diana), Das, S. (Shikta), Elliott, P. (P.), Evans, D.M. (D. M.), Feenstra, B. (B.), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Freathy, R.M. (Rachel), Gaillard, R. (R.), Geller, F. (Frank), Groen-Blokhuis, M. (Maria), Goh, L.K. (L. K.), Guxens Junyent, M. (Mònica), Hattersley, A.T. (Andrew), Haworth, C.M.A. (Claire M.), Hadley, D. (D.), Heinrich, J. (J.), Hirschhorn, J.N. (Joel), Hocher, B. (Berthold), Holloway, J.W. (J. W.), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (E.), Iñiguez, C. (C.), Jaddoe, V.W. (V. W.), Jarvelin, M.R. (M. R.), Kaakinen, M. (M.), Kilpeläinen, T.O. (Tuomas), Hypponen, E. (Elina), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Cooper, C. (Charles), Lange, L.A. (Leslie), Lawlor, D.A. (D. A.), Lehtimäki, T. (Terho), Lewin, A. (Alex), Elliott, P. (Paul), Lindi, V. (Virpi), Maggi, R. (Reedik), Feenstra, B. (Bjarke), McCarthy, M.I. (M. I.), Melbye, M. (Mads), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (D. O.), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Oken, E. (Emily), Ong, K.K. (K. K.), O'Reilly, P.F. (P. F.), Palmer, C. (Cameron), Panoutsopoulou, K. (K.), Pararajasingham, J. (Jennifer), Pearson, E.R. (E. R.), Pennell, C.E. (Craig), Power, C. (Christopher), Price, T.S. (Thomas), Prokopenko, I. (Inga), Raitakari, O.T. (O. T.), Rodriguez, A. (A.), Salem, R.M. (Rany), Saw, S.M. (S. M.), Sebert, S. (S.), Siitonen, N. (Niina), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Sovio, U. (Ulla), Lawlor, D.A. (Debbie), Sunyer, J. (J.), Taal, H.R. (Rob), Teo, Y.Y. (Y. Y.), Thiering, E. (Elisabeth), Tiesler, C. (C.), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Valcárcel, B. (Beatriz), Teo, Y.Y. (Yik Ying), White, S.J. (Stefan), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (J. F.), Yaghootkar, H. (H.), Elks, C.E. (Cathy), Perry, J.R. (J. R.), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (C.), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (E. M.), Gudbjartsson, D.F. (Daniel), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (P.), Mangino, M. (Massimo), Byrne, E.M. (Enda), Smith, A.V. (Albert), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (J. H.), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Smith, A.V. (Davey), Chanock, S.J. (Stephen), Warrington, M. (M.), Zgaga, L. (L.), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (T.), Ulivi, S. (Shelia), Sunyer, J. (Jordi), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Boerwinkle, E. (E.), Buring, J.E. (Julie), Busonero, F. (F.), Barroso, I.E. (Inês), Chanock, S.J. (S. J.), Warrington, N.M. (Nicole), Couper, D.J. (David), Coviello, A.D. (Andrea), Busonero, F., Faire, U. (Ulf) de, de Geus, E.J. (E. J.), Deloukas, P. (Panagiotis), Döring, A. (Angela), Davey Smith, G. (G.), Adamo, P. (Pio) d', Eiriksdottir, G. (Gudny), Geus, E.J.C. (Eco) de, Hagen, K. (Knut), Ferrucci, L. (L.), Folsom, A.R. (A. R.), Foroud, T. (T.), Garcia, M.E. (M.), Gasparini, P. (P.), Gieger, C. (Christian), Gudnason, V. (V.), Folsom, A.R. (Aaron), Hankinson, S.E. (S. E.), Ferreli, L. (Liana), Gasparini, P. (Paolo), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (F. B.), Illig, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K.T. (K. T.), Kiel, D.P. (Douglas P.), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S. (J. S.), Li, S. (S.), Liu, J. (J.), Levy, D. (D.), Martin, N.G. (N. G.), Aspelund, T. (Thor), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (M.), Ness, A.R. (A. R.), Boerwinkle, E.A. (Eric), Oostra, B.A. (Ben), Peacock, M. (M.), Pare, G. (Guillame), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Cornelis, M. (Marilyn), Polasek, O. (Ozren), Plump, A.S. (A. S.), Peacock, M. (Munro), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Rivadeneira, F. (F.), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (D.), Scuteri, A. (A.), Segrè, A.V. (Ayellet), Foroud, T. (Tatiana), Srinivasan, S.R. (Sathanur), Tammesoo, M.L. (M. L.), Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Scuteri, A. (Angelo), Tryggvadottir, L. (Laufey), Tyrer, J. (J.), Uda, M. (M.), van Dam, R.M. (R. M.), Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weedon, M.N. (Michael), Wright, A.F. (Alan), Young, L. (L.), Zhai, G. (G.), Zhuang, W.V. (W. V.), Bierut, L.J. (L. J.), Boyd, H.A. (H. A.), Crisponi, L. (Laura), Demerath, E.W. (E. W.), Duijn, C.M. (Cornelia) van, Econs, M.J. (M. J.), Harris, T.B. (Tamara), Bierut, L.J. (Laura), Loos, R.J.F. (Ruth), Ridker, P.M. (Paul), Demerath, E.W. (Ellen), Streeten, E.A. (Elizabeth), Econs, M.J. (Michael), Thorsteinsdottir, U. (Unnur), Widen, E. (E.), Murabito, J. (Joanne), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Crawford, S. (Steve), Crow, S. (Scott), Fichter, M.M. (M. M.), Halmi, K.A. (K. A.), Palotie, A. (Aarno), La Via, M. (Maria), Mitchell, J. (James), Strober, M. (Michael), Rotondo, A. (Alessandro), Woodside, D.B. (D Blake), Keel, P. (Pamela), Lilenfeld, L. (Lisa), Rivadeneira Ramirez, F. (Fernando), Magistretti, P. (Pierre), Montgomery, G.W. (G. W.), Hinney, A. (Anke), Kesselmeier, M. (M.), Jall, S. (S.), Volckmar, A.-L. (A. L.), Föcker, M. (M.), Antel, J. (J.), Heid, I.M. (Iris), Winkler, T.W. (Thomas W.), Grant, S.F.A. (S. F.A.), Guo, Y. (Yongli), Bergen, A.W. (Andrew), Grant, S.F.A. (Struan), Berrettini, W. (Wade), Hakonarson, H. (Hakon), Herpertz-Dahlmann, B. (B.), De Zwaan, M. (M.), Herzog, W. (W.), Ehrlich, S.M. (Stefan), Zipfel, S. (S.), Egberts, K. (Karin), Adan, R. (R.), Brandys, M. (M.), Elburg, A.A. (Annemarie) van, Boraska Perica, V. (V.), Müller, T.D., Tschöp, M.H. (M. H.), Zeggini, E. (Eleftheria), Bulik, C.M. (C. M.), Collier, D.A. (David), Scherag, A. (A.), Hebebrand, J. (J.), Tschop, M. (Matthias), Floyd, J. (Jamie), Thornton, L.M. (Laura), Huckins, L.M. (Laura M), Southam, L. (Lorraine), Rayner, N.W. (Nigel William), Tachmazidou, I. (Ioanna), Klump, K.L. (K. L.), Treasure, J. (Janet), Lewis, C.M. (Cathryn), Schmidt, U. (Ulrike), Tozzi, F. (Federica), Iezebrink, K. (Kirsty), Gorwood, P. (Philip), Kas, M.J.H. (Martien), Favaro, A. (Angela), Santonastaso, P. (Paolo), Fernández-Aranda, F. (Fernando), Gratacos, M. (Monica), Rybakowski, F. (Filip), Dmitrzak-Weglarz, M. (Monika), Kaprio, J. (Jaakko), Keski-Rahkonen, A. (Anna), Raevuori-Helkamaa, A. (Anu), Furth, E.F. (Eric) van, Slof-Op’t Landt, M.C.T. (Margarita C. T.), Hudson, J.I. (James I), Knudsen, G.P.S. (Gun Peggy S.), Monteleone, P. (Palmiero), Kaplan, A.S. (Allan S), Karwautz, A. (Andreas), Li, D. (Dong), Komaki, G. (Gen), Ando, T. (Tetsuya), Inoko, H. (Hidetoshi), Esko, T. (T.), Fischer, K. (Krista), Männik, K. (Katrin), Metspalu, A. (Andres), Baker, J.H. (Jessica H), Cone, R.D. (Roger D), Esko, T. (Tõnu), DeSocio, J.E. (Janiece E), Hilliard, C.E. (Christopher E), O’Toole, J.K. (Julie K), Pantel, J. (Jacques), Szatkiewicz, J.P. (Jin P), Taico, C. (Chrysecolla), Zerwas, S. (Stephanie), Trace, S.E. (Sara E), Davis, O.S.P. (Oliver S.), Helder, S. (Sietske), Bühren, K. (Katharina), Burghardt, R. (Roland), Imgart, H. (Hartmut), Scherag, A. (Andre), Boni, C. (Claudette), Ramoz, N. (Nicolas), Versini, A. (Audrey), Danner, U.N. (Unna N), de Kove, C. (Carolien), Hendriks, J. (Judith), Koeleman, B.P.C. (Bobby P. C.), Ophoff, R.A. (Roel), Strengman, E. (Eric), Bruson, A. (Alice), Clementi, M. (Maurizio), Degortes, D. (Daniela), Forzan, M. (Monica), Tenconi, E. (Elena), Docampo, E. (Elisa), Jiménez-Murcia, G.E.S. (Geòrgia Escaramí Susana), Lissowska, J. (Jolanta), Rajewski, A. (Andrzej), Szeszenia-Dabrowska, N. (Neonila), Slopien, A. (Agnieszka), Hauser, J. (J.), Karhunen, L. (Leila), Meulenbelt, I. (Ingrid), Slagboom, P.E. (Eline), Tortorella, A. (Alfonso), Maj, M. (Mario), Dedoussis, G.V. (George), Dedoussis, G.V. (G. V.), Koeleman, B.P.C. (Bobby), Gonidakis, F. (Fragiskos), Tziouvas, K. (Konstantinos), Tsitsika, A. (Artemis), Papezova, H. (Hana), Slachtova, L. (Lenka), Martaskova, D. (Debora), Kennedy, J.L., Levitan, R.D. (Robert D), Yilmaz, Z. (Zeynep), Huemer, J. (Julia), Koubek, D. (Doris), Merl, E. (Elisabeth), Wagner, G. (Gudrun), Lichtenstein, P. (Paul), Breen, G. (Gerome), Cohen-Woods, S. (Sarah), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Cichon, S. (Sven), Giegling, I. (Ina), Herms, S. (Stefan), Rujescu, D. (Dan), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Sladek, R. (Rob), Gambaro, G. (Giovanni), Soranzo, N. (Nicole), Julia, A. (Antonio), Marsal, S. (Sara), Rabionet, R. (Raquel), Gaborieau, V. (Valerie), Dick, D.M. (Danielle), Palotie, A. (A.), Ripatti, S. (Samuli), Widen, E., Espeseth, T. (Thomas), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Steen, V.M. (Vidar), Le Hellard, S. (Stephanie), Mattingsdal, M. (Morten), Ntalla, I. (Ioanna), Bencko, V. (Vladimir), Foretova, L. (Lenka), Janout, V. (Vladimir), Navratilova, M. (Marie), Pinto, D. (Dalila), Scherer, S.W. (Stephen W), Carlberg, L. (Laura), Schosser, A. (Alexandra), Alfredsson, L. (Lars), Pinto, D. (Duane), Scherer, S.W. (Stephen), Padyukov, L. (Leonid), Finan, C. (Chris), Kalsi, G. (Gursharan), Roberts, M. (Marion), Logan, D.W. (Darren W), Peltonen, L. (Leena Johanna), Ritchie, G.R.S. (Graham R.S.), Barrett, J.C. (Jeffrey), Estivill, X. (Xavier), Sullivan, P.F. (Patrick), Anderson, C.A. (Carl A), McGinnis, R. (Ralph), Sambrook, J. (Jennifer), Stephens, J. (Jonathan), Ouwehand, W.H. (Willem), McArdle, P.F. (P. F.), Ring, S.M. (Susan), Strachan, D.P. (David), Alexander, G. (Graeme), Conlon, P.J. (Peter J), Dominiczak, A. (Anna), Duncanson, A. (Audrey), Padyukov, L. (L.), Langford, C. (Cordelia), Lord, G. (Graham), Conlon, P. (Peter), Sandford, R. (Richard), Sheerin, N. (Neil), Vannberg, F.O. (Frederik O), Blackburn, H. (Hannah), Maxwell, A.P. (A.), Edkins, T. (Ted), Gillman, M.W. (Matthew W.), Gray, E. (Emma), Hunt, S.E. (Sarah E), Nengut, S.-G. (Suna-Gumuscu), Potter, S.C. (Simon), Rich, S.S. (Stephen), Simpkin, D. (Douglas), Whittaker, P. (Pamela), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N. (N.), Benke, K. (K.), Berry, D. (Diane), Boomsma, D.I. (Dorret), Bradfield, J.P. (Jonathan), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cooper, C. (C.), Cousminer, D.L. (Diana), Das, S. (Shikta), Elliott, P. (P.), Evans, D.M. (D. M.), Feenstra, B. (B.), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Freathy, R.M. (Rachel), Gaillard, R. (R.), Geller, F. (Frank), Groen-Blokhuis, M. (Maria), Goh, L.K. (L. K.), Guxens Junyent, M. (Mònica), Hattersley, A.T. (Andrew), Haworth, C.M.A. (Claire M.), Hadley, D. (D.), Heinrich, J. (J.), Hirschhorn, J.N. (Joel), Hocher, B. (Berthold), Holloway, J.W. (J. W.), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (E.), Iñiguez, C. (C.), Jaddoe, V.W. (V. W.), Jarvelin, M.R. (M. R.), Kaakinen, M. (M.), Kilpeläinen, T.O. (Tuomas), Hypponen, E. (Elina), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Cooper, C. (Charles), Lange, L.A. (Leslie), Lawlor, D.A. (D. A.), Lehtimäki, T. (Terho), Lewin, A. (Alex), Elliott, P. (Paul), Lindi, V. (Virpi), Maggi, R. (Reedik), Feenstra, B. (Bjarke), McCarthy, M.I. (M. I.), Melbye, M. (Mads), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (D. O.), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Oken, E. (Emily), Ong, K.K. (K. K.), O'Reilly, P.F. (P. F.), Palmer, C. (Cameron), Panoutsopoulou, K. (K.), Pararajasingham, J. (Jennifer), Pearson, E.R. (E. R.), Pennell, C.E. (Craig), Power, C. (Christopher), Price, T.S. (Thomas), Prokopenko, I. (Inga), Raitakari, O.T. (O. T.), Rodriguez, A. (A.), Salem, R.M. (Rany), Saw, S.M. (S. M.), Sebert, S. (S.), Siitonen, N. (Niina), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Sovio, U. (Ulla), Lawlor, D.A. (Debbie), Sunyer, J. (J.), Taal, H.R. (Rob), Teo, Y.Y. (Y. Y.), Thiering, E. (Elisabeth), Tiesler, C. (C.), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Valcárcel, B. (Beatriz), Teo, Y.Y. (Yik Ying), White, S.J. (Stefan), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (J. F.), Yaghootkar, H. (H.), Elks, C.E. (Cathy), Perry, J.R. (J. R.), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (C.), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (E. M.), Gudbjartsson, D.F. (Daniel), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (P.), Mangino, M. (Massimo), Byrne, E.M. (Enda), Smith, A.V. (Albert), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (J. H.), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Smith, A.V. (Davey), Chanock, S.J. (Stephen), Warrington, M. (M.), Zgaga, L. (L.), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (T.), Ulivi, S. (Shelia), Sunyer, J. (Jordi), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Boerwinkle, E. (E.), Buring, J.E. (Julie), Busonero, F. (F.), Barroso, I.E. (Inês), Chanock, S.J. (S. J.), Warrington, N.M. (Nicole), Couper, D.J. (David), Coviello, A.D. (Andrea), Busonero, F., Faire, U. (Ulf) de, de Geus, E.J. (E. J.), Deloukas, P. (Panagiotis), Döring, A. (Angela), Davey Smith, G. (G.), Adamo, P. (Pio) d', Eiriksdottir, G. (Gudny), Geus, E.J.C. (Eco) de, Hagen, K. (Knut), Ferrucci, L. (L.), Folsom, A.R. (A. R.), Foroud, T. (T.), Garcia, M.E. (M.), Gasparini, P. (P.), Gieger, C. (Christian), Gudnason, V. (V.), Folsom, A.R. (Aaron), Hankinson, S.E. (S. E.), Ferreli, L. (Liana), Gasparini, P. (Paolo), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (F. B.), Illig, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K.T. (K. T.), Kiel, D.P. (Douglas P.), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S. (J. S.), Li, S. (S.), Liu, J. (J.), Levy, D. (D.), Martin, N.G. (N. G.), Aspelund, T. (Thor), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (M.), Ness, A.R. (A. R.), Boerwinkle, E.A. (Eric), Oostra, B.A. (Ben), Peacock, M. (M.), Pare, G. (Guillame), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Cornelis, M. (Marilyn), Polasek, O. (Ozren), Plump, A.S. (A. S.), Peacock, M. (Munro), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Rivadeneira, F. (F.), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (D.), Scuteri, A. (A.), Segrè, A.V. (Ayellet), Foroud, T. (Tatiana), Srinivasan, S.R. (Sathanur), Tammesoo, M.L. (M. L.), Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Scuteri, A. (Angelo), Tryggvadottir, L. (Laufey), Tyrer, J. (J.), Uda, M. (M.), van Dam, R.M. (R. M.), Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weedon, M.N. (Michael), Wright, A.F. (Alan), Young, L. (L.), Zhai, G. (G.), Zhuang, W.V. (W. V.), Bierut, L.J. (L. J.), Boyd, H.A. (H. A.), Crisponi, L. (Laura), Demerath, E.W. (E. W.), Duijn, C.M. (Cornelia) van, Econs, M.J. (M. J.), Harris, T.B. (Tamara), Bierut, L.J. (Laura), Loos, R.J.F. (Ruth), Ridker, P.M. (Paul), Demerath, E.W. (Ellen), Streeten, E.A. (Elizabeth), Econs, M.J. (Michael), Thorsteinsdottir, U. (Unnur), Widen, E. (E.), Murabito, J. (Joanne), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Crawford, S. (Steve), Crow, S. (Scott), Fichter, M.M. (M. M.), Halmi, K.A. (K. A.), Palotie, A. (Aarno), La Via, M. (Maria), Mitchell, J. (James), Strober, M. (Michael), Rotondo, A. (Alessandro), Woodside, D.B. (D Blake), Keel, P. (Pamela), Lilenfeld, L. (Lisa), Rivadeneira Ramirez, F. (Fernando), Magistretti, P. (Pierre), and Montgomery, G.W. (G. W.)
Abstract: The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the associa
Published: 2017
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6. Correction: The complex genetics of gait speed: Genome-wide metaanalysis approach [Aging, (Albany NY), 9, 1, (2017), (209-246)]doi 10.18632/aging.101151

Author: Ben-Avraham, D. (Dan), Karasik, D. (David), Verghese, J. (Joe), Lunetta, K.L. (Kathryn), Smith, J.A. (Jennifer A), Eicher, J.D. (John D.), Vered, R. (Rotem), Deelen, J. (Joris), Arnold, A.M. (Alice), Buchman, A.S. (Aron), Tanaka, T. (Toshiko), Faul, J.D. (Jessica D.), Nethander, M. (Maria), Fornage, M. (Myriam), Adams, H.H.H. (Hieab), Matteini, A.M. (Amy M.), Callisaya, M. (Michele), Smith, A.V. (Albert Vernon), Yu, L. (Lei), Jager, P.L. (Philip) de, Evans, D.A. (Denis), Gudnason, V. (Vilmundur), Hofman, A. (Albert), Pattie, A. (Alison), Corley, J. (Janie), Launer, L.J. (Lenore), Knopman, D.S. (Davis S.), Parimi, N. (Neeta), Turner, S.T. (Stephen T.), Bandinelli, S. (Stefania), Beekman, M. (Marian), Gutman, D. (Danielle), Sharvit, L. (Lital), Mooijaart, S.P. (Simon), Liewald, D.C.M. (David), Houwing-Duistermaat, J.J. (Jeanine), Ohlsson, C. (Claes), Moed, H. (Heleen), Verlinden, V.J.A. (Vincent), Mellström, D. (Dan), Geest, J.N. (Jos) van der, Karlsson, M. (Magnus), Hernandez, D.G. (Dena), McWhirter, R. (Rebekah), Liu, Y. (YongMei), Thomson, R. (Russell), Tranah, G.J. (Gregory), Uitterlinden, A.G. (André), Weir, D.R. (David R.), Zhao, W. (Wei), Starr, J.M. (John), Johnson, A.D. (Andrew), Ikram, M.A. (Arfan), Bennett, D.A. (David), Cummings, S., Deary, I.J. (Ian), Harris, T.B. (Tamara), Kardia, S.L.R. (Sharon L.R.), Mosley, T.H. (Thomas H.), Srikanth, V. (Velandai), Windham, B.G. (Gwen), Newman, A.B. (Anne B.), Walston, J. (Jeremy), Davies, G. (Gail), Evans, D.S. (Daniel), Slagboom, P.E. (Eline), Ferrucci, L. (Luigi), Kiel, D.P. (Douglas P.), Murabito, J. (Joanne), Atzmon, G. (Gil), Ben-Avraham, D. (Dan), Karasik, D. (David), Verghese, J. (Joe), Lunetta, K.L. (Kathryn), Smith, J.A. (Jennifer A), Eicher, J.D. (John D.), Vered, R. (Rotem), Deelen, J. (Joris), Arnold, A.M. (Alice), Buchman, A.S. (Aron), Tanaka, T. (Toshiko), Faul, J.D. (Jessica D.), Nethander, M. (Maria), Fornage, M. (Myriam), Adams, H.H.H. (Hieab), Matteini, A.M. (Amy M.), Callisaya, M. (Michele), Smith, A.V. (Albert Vernon), Yu, L. (Lei), Jager, P.L. (Philip) de, Evans, D.A. (Denis), Gudnason, V. (Vilmundur), Hofman, A. (Albert), Pattie, A. (Alison), Corley, J. (Janie), Launer, L.J. (Lenore), Knopman, D.S. (Davis S.), Parimi, N. (Neeta), Turner, S.T. (Stephen T.), Bandinelli, S. (Stefania), Beekman, M. (Marian), Gutman, D. (Danielle), Sharvit, L. (Lital), Mooijaart, S.P. (Simon), Liewald, D.C.M. (David), Houwing-Duistermaat, J.J. (Jeanine), Ohlsson, C. (Claes), Moed, H. (Heleen), Verlinden, V.J.A. (Vincent), Mellström, D. (Dan), Geest, J.N. (Jos) van der, Karlsson, M. (Magnus), Hernandez, D.G. (Dena), McWhirter, R. (Rebekah), Liu, Y. (YongMei), Thomson, R. (Russell), Tranah, G.J. (Gregory), Uitterlinden, A.G. (André), Weir, D.R. (David R.), Zhao, W. (Wei), Starr, J.M. (John), Johnson, A.D. (Andrew), Ikram, M.A. (Arfan), Bennett, D.A. (David), Cummings, S., Deary, I.J. (Ian), Harris, T.B. (Tamara), Kardia, S.L.R. (Sharon L.R.), Mosley, T.H. (Thomas H.), Srikanth, V. (Velandai), Windham, B.G. (Gwen), Newman, A.B. (Anne B.), Walston, J. (Jeremy), Davies, G. (Gail), Evans, D.S. (Daniel), Slagboom, P.E. (Eline), Ferrucci, L. (Luigi), Kiel, D.P. (Douglas P.), Murabito, J. (Joanne), and Atzmon, G. (Gil)
Abstract: Applying HaploReg v4.1 analysis to the 536 variants resulted in 9 categories (Supplementary Table 8): miscRNA (1 variant); snoRNA (2 variants); microRNA (4 variants); snRNA (9 variants); pseudogenes (14 variants); sequencing in progress (43 variants); LINC RNA (86 variants); and 372 variants within protein coding genes. In addition, some variants annotate to the same gene resulting in a total of 139 genes (protein-coding or non-coding). Of those genes, 6 are exceptionally long, containing over a million base-pairs, the longest of which is PTPRT coded by 1117219bp. The shortest genes are the ones coding for micro (MIR3143) or small nuclear (U7) RNAs at 63bp each. There is only partial information regarding the chromatin state of each variant. However, from the information gathered in the analysis we observed 14 transcription start sites and 245 enhancers (Supplementary Table 8).
Published: 2017
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7. Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis

Author: Manousaki, D. (Despoina), Dudding, T. (Tom), Haworth, S. (Simon), Hsu, Y.-H. (Yi-Hsiang), Liu, C.-T. (Ching-Ti), Medina-Gomez, M.C. (Carolina), Voortman, R.G. (Trudy), Velde, N. (Nathalie) van der, Melhus, H. (Håkan), Robinson-Cohen, C. (Cassianne), Cousminer, D.L. (Diana), Nethander, M. (Maria), Vandenput, L. (Liesbeth), Noordam, R., Forgetta, V. (Vincenzo), Greenwood, C.M.T. (Celia), Biggs, M.L. (M.), Psaty, B.M. (Bruce M.), Rotter, J.I. (Jerome I.), Zemel, B.S. (Babette S.), Mitchell, J.A. (Jonathan A.), Taylor, B. (Bruce), Lorentzon, M. (Mattias), Karlsson, M. (Magnus), Jaddoe, V.W.V. (Vincent), Tiemeier, H.W. (Henning), Campos Obando, N. (Natalia), Franco, O.H. (Oscar), Uitterlinden, A.G. (André), Broer, L. (Linda), Schoor, N.M. (Natasja) van, Ham, A.C. (Annelies), Ikram, M.K. (Kamran), Karasik, D. (David), Mutsert, R. (Reneé) de, Rosendaal, F.R. (Frits), Heijer, M. (Martin) den, Wang, T.J. (Thomas), Kao, W.H.L. (Wen), Orwoll, E.S. (Eric), Mook-Kanamori, D.O. (Dennis), Michaëlsson, K. (Karl), Kestenbaum, B. (Bryan), Ohlsson, C. (Claes), Mellström, D. (Dan), Groot, L.C.P.G.M. (Lisette) de, Grant, S.F.A. (Struan), Kiel, D.P. (Douglas P.), Zillikens, M.C. (Carola), Rivadeneira Ramirez, F. (Fernando), Sawcer, S.J. (Stephen), Timpson, N.J. (Nicholas), Richards, J.B. (Brent), Manousaki, D. (Despoina), Dudding, T. (Tom), Haworth, S. (Simon), Hsu, Y.-H. (Yi-Hsiang), Liu, C.-T. (Ching-Ti), Medina-Gomez, M.C. (Carolina), Voortman, R.G. (Trudy), Velde, N. (Nathalie) van der, Melhus, H. (Håkan), Robinson-Cohen, C. (Cassianne), Cousminer, D.L. (Diana), Nethander, M. (Maria), Vandenput, L. (Liesbeth), Noordam, R., Forgetta, V. (Vincenzo), Greenwood, C.M.T. (Celia), Biggs, M.L. (M.), Psaty, B.M. (Bruce M.), Rotter, J.I. (Jerome I.), Zemel, B.S. (Babette S.), Mitchell, J.A. (Jonathan A.), Taylor, B. (Bruce), Lorentzon, M. (Mattias), Karlsson, M. (Magnus), Jaddoe, V.W.V. (Vincent), Tiemeier, H.W. (Henning), Campos Obando, N. (Natalia), Franco, O.H. (Oscar), Uitterlinden, A.G. (André), Broer, L. (Linda), Schoor, N.M. (Natasja) van, Ham, A.C. (Annelies), Ikram, M.K. (Kamran), Karasik, D. (David), Mutsert, R. (Reneé) de, Rosendaal, F.R. (Frits), Heijer, M. (Martin) den, Wang, T.J. (Thomas), Kao, W.H.L. (Wen), Orwoll, E.S. (Eric), Mook-Kanamori, D.O. (Dennis), Michaëlsson, K. (Karl), Kestenbaum, B. (Bryan), Ohlsson, C. (Claes), Mellström, D. (Dan), Groot, L.C.P.G.M. (Lisette) de, Grant, S.F.A. (Struan), Kiel, D.P. (Douglas P.), Zillikens, M.C. (Carola), Rivadeneira Ramirez, F. (Fernando), Sawcer, S.J. (Stephen), Timpson, N.J. (Nicholas), and Richards, J.B. (Brent)
Abstract: Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency synonymous coding variant g.14900931G>A, which conferred a large effect on 25-hydroxyvitamin D levels. The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency. Individuals carrying one copy of this variant also had increased odds of multiple sclerosis in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin
Published: 2017
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8. Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus

Author: Medina-Gomez, M.C. (Carolina), Kemp, J.P. (John), Dimou, N.L. (Niki L.), Kreiner, E. (Eskil), Chesi, A. (Alessandra), Zemel, B.S. (Babette S.), Bønnelykke, K. (Klaus), Boer, C.G. (Cindy G.), Ahluwalia, T.S. (Tarunveer Singh), Bisgaard, H. (Hans), Evangelou, E. (Evangelos), Heppe, D.H.M. (Denise), Bonewald, L.F. (Lynda F.), Gorski, J.P. (Jeffrey P.), Ghanbari, M. (Mohsen), Demissie, S. (Serkalem), Duque, G. (Gustavo), Maurano, M.T. (Matthew T.), Kiel, D.P. (Douglas P.), Hsu, Y.-H. (Yi-Hsiang), Eerden, B.C.J. (Bram) van der, Ackert-Bicknell, C. (Cheryl), Reppe, S. (Sjur), Gautvik, K.M. (Kaare), Raastad, T. (Truls), Karasik, D. (David), Peppel, J. (Jeroen) van de, Jaddoe, V.W.V. (Vincent), Uitterlinden, A.G. (André), Tobias, J.H. (Jon), Grant, S.F.A. (Struan), Bagos, P.G. (Pantelis G.), Evans, D.M. (David), Rivadeneira Ramirez, F. (Fernando), Medina-Gomez, M.C. (Carolina), Kemp, J.P. (John), Dimou, N.L. (Niki L.), Kreiner, E. (Eskil), Chesi, A. (Alessandra), Zemel, B.S. (Babette S.), Bønnelykke, K. (Klaus), Boer, C.G. (Cindy G.), Ahluwalia, T.S. (Tarunveer Singh), Bisgaard, H. (Hans), Evangelou, E. (Evangelos), Heppe, D.H.M. (Denise), Bonewald, L.F. (Lynda F.), Gorski, J.P. (Jeffrey P.), Ghanbari, M. (Mohsen), Demissie, S. (Serkalem), Duque, G. (Gustavo), Maurano, M.T. (Matthew T.), Kiel, D.P. (Douglas P.), Hsu, Y.-H. (Yi-Hsiang), Eerden, B.C.J. (Bram) van der, Ackert-Bicknell, C. (Cheryl), Reppe, S. (Sjur), Gautvik, K.M. (Kaare), Raastad, T. (Truls), Karasik, D. (David), Peppel, J. (Jeroen) van de, Jaddoe, V.W.V. (Vincent), Uitterlinden, A.G. (André), Tobias, J.H. (Jon), Grant, S.F.A. (Struan), Bagos, P.G. (Pantelis G.), Evans, D.M. (David), and Rivadeneira Ramirez, F. (Fernando)
Abstract: Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% for TBLH-BMD, and 39% for TB-LM, with a shared genetic component of 43%. We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: _WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5_. Variants in the _TOM1L2/SREBF1_ locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that _SREBF1_ is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass.
Published: 2017
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9. Gene transcripts associated with muscle strength: A CHARGE meta-analysis of 7,781 persons

Author: Pilling, L.C. (Luke), Joehanes, R. (Roby), Kacprowski, T. (Tim), Peters, M.J. (Marjolein), Jansen, R., Karasik, D. (David), Kiel, D.P. (Douglas P.), Harries, L.W. (Lorna), Teumer, A. (Alexander), Powell, J., Levy, D. (Daniel), Lin, H., Lunetta, K.L. (Kathryn), Munson, P.J. (Peter), Bandinelli, S. (Stefania), Henley, W., Hernandez, D.G. (Dena), Singleton, A., Tanaka, T., Grootheest, G. (Gerard) van, Hofman, A. (Albert), Uitterlinden, A.G. (André), Biffar, R. (Reiner), Gläser, S., Homuth, G. (Georg), Malsch, C., Völker, U. (Uwe), Penninx, B.W.J.H. (Brenda W.J.H.), Meurs, J.B.J. (Joyce) van, Ferrucci, L. (Luigi), Kocher, T., Murabito, J. (Joanne), Melzer, D. (David), Pilling, L.C. (Luke), Joehanes, R. (Roby), Kacprowski, T. (Tim), Peters, M.J. (Marjolein), Jansen, R., Karasik, D. (David), Kiel, D.P. (Douglas P.), Harries, L.W. (Lorna), Teumer, A. (Alexander), Powell, J., Levy, D. (Daniel), Lin, H., Lunetta, K.L. (Kathryn), Munson, P.J. (Peter), Bandinelli, S. (Stefania), Henley, W., Hernandez, D.G. (Dena), Singleton, A., Tanaka, T., Grootheest, G. (Gerard) van, Hofman, A. (Albert), Uitterlinden, A.G. (André), Biffar, R. (Reiner), Gläser, S., Homuth, G. (Georg), Malsch, C., Völker, U. (Uwe), Penninx, B.W.J.H. (Brenda W.J.H.), Meurs, J.B.J. (Joyce) van, Ferrucci, L. (Luigi), Kocher, T., Murabito, J. (Joanne), and Melzer, D. (David)
Abstract: Lower muscle strength in midlife predicts disability and mortality in later life. Blood-borne factors, including growth differentiation factor 11 (GDF11), have been linked to muscle regeneration in animal models. We aimed to identify gene transcripts associated with muscle strength in adults. Meta-analysis of whole blood gene expression (overall 17,534 unique genes measured by microarray) and hand-grip strength in four independent cohorts (n = 7,781, ages: 20–104 yr, weighted mean = 56), adjusted for age, sex, height, weight, and leukocyte subtypes. Separate analyses were performed in subsets (older/younger than 60, men/women). Expression levels of 221 genes were associated with strength after adjustment for cofactors and for multiple statistical testing, including ALAS2 (rate-limiting enzyme in heme synthesis), PRF1 (perforin, a cytotoxic protein associated with inflammation), IGF1R, and IGF2BP2 (both insulin l
Published: 2016
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10. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture

Author: Zheng, H.-F. (Hou-Feng), Forgetta, V. (Vincenzo), Hsu, Y.-H. (Yi-Hsiang), Estrada Gil, K. (Karol), Rosello-Diez, A. (Alberto), Leo, P.J. (Paul), Dahia, C.L. (Chitra L.), Park-Min, K.H. (Kyung Hyun), Tobias, J.H. (Jon), Kooperberg, C. (Charles), Kleinman, A. (Aaron), Styrkarsdottir, U. (Unnur), Liu, C.-T. (Ching-Ti), Uggla, C. (Charlotta), Evans, D.S. (Daniel), Nielson, C. (Carrie), Walter, K. (Klaudia), Pettersson-Kymmer, U. (Ulrika), McCarthy, S. (Shane), Eriksson, J. (Joel), Kwan, T. (Tony), Jhamai, M. (Mila), Trajanoska, K. (Katerina), Memari, Y. (Yasin), Min, J.L. (Josine L.), Huang, J. (Jie), Danecek, P. (Petr), Wilmot, B. (Beth), Li, R. (Rui), Chou, W.-C. (Wen-Chi), Mokry, L.E. (Lauren E.), Moayyeri, A. (Alireza), Claussnitzer, M. (Melina), Cheng, C.-H. (Chia-Ho), Cheung, W. (Warren), Medina-Gomez, M.C. (Carolina), Ge, B. (Bing), Chen, S.-H. (Shu-Huang), Choi, K. (Kunho), Oei, L. (Ling), Fraser, J. (James), Kraaij, R. (Robert), Hibbs, M.A. (Matthew A.), Gregson, C.L. (Celia L.), Paquette, D. (Denis), Hofman, A. (Albert), Wibom, C. (Carl), Tranah, G.J. (Gregory), Marshall, M. (Mhairi), Gardiner, B.B. (Brooke B.), Cremin, K. (Katie), Auer, P. (Paul), Hsu, L. (Li), Ring, S. (Susan), Tung, J.Y. (Joyce Y.), Thorleifsson, G. (Gudmar), Enneman, A.W. (Anke), Schoor, N.M. (Natasja) van, Groot, L.C.P.G.M. (Lisette) de, Velde, N. (Nathalie) van der, Melin, B. (Beatrice), Kemp, J.P. (John), Christiansen, C., Sayers, I. (Ian), Zhou, Y. (Yanhua), Calderari, S. (Sophie), Rooij, J.G.J. (Jeroen) van, Carlson, C. (Chris), Peters, U. (Ulrike), Berlivet, S. (Soizik), Dostie, J. (Josée), Uitterlinden, A.G. (André), Williams, S.R. (Stephen R.), Farber, C. (Charles), Grinberg, D. (Daniel), LaCroix, A.Z. (Andrea), Haessler, J. (Jeff), Chasman, D.I. (Daniel), Giulianini, F. (Franco), Rose, L.M. (Lynda M.), Ridker, P.M. (Paul), Eisman, J.A. (John), Nguyen, T.V. (Tuan), Center, J.R. (Jacqueline), Nogues, X. (Xavier), Garcia-Giralt, N. (Natàlia), Launer, L.J. (Lenore), Gudnason, V. (Vilmunder), Mellström, D. (Dan), Vandenput, L. (Liesbeth), Amin, N. (Najaf), Duijn, C.M. (Cornelia) van, Karlsson, M. (Magnus), Ljunggren, O. (Östen), Svensson, O. (Olle), Hallmans, G. (Göran), Rousseau, M.F. (Francois), Giroux, S. (Sylvie), Bussière, J. (Johanne), Arp, P.P. (Pascal), Koromani, F. (Fjorda), Prince, R.L. (Richard L.), Lewis, J.R. (Joshua), Langdahl, B.L. (Bente), Hermann, A.P. (A. Pernille), Jensen, J.-E.B. (Jens-Erik B.), Kaptoge, S. (Stephen), Khaw, K.T., Reeve, J. (Jonathan), Formosa, M.M. (Melissa M.), Xuereb-Anastasi, A. (Angela), Åkesson, K. (Kristina), McGuigan, F.E., Garg, G. (Gaurav), Olmos, D. (David), Zarrabeitia, M.T. (María), Riancho, J.A. (José), Ralston, S.H. (Stuart), Alonso, N. (Nerea), Jiang, X. (Xi), Goltzman, D. (David), Pastinen, T. (Tomi), Grundberg, E. (Elin), Gauguier, D. (Dominique), Orwoll, E.S. (Eric), Karasik, D. (David), Smith, A.V. (Davey), Siggeirsdottir, K. (Kristin), Harris, T.B. (Tamara), Zillikens, M.C. (Carola), Meurs, J.B.J. (Joyce) van, Thorsteinsdottir, U. (Unnur), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Soranzo, N. (Nicole), Durbin, R. (Richard), Wilson, S.G. (Scott), Ntzani, E.E. (Evangelia), Brown, M.A. (Matthew), Zwart, J-A. (John-Anker), Hinds, D.A. (David A.), Spector, T.D. (Timothy), Cupples, L.A. (Adrienne), Ohlsson, C. (Claes), Greenwood, C.M.T. (Celia), Jackson, R.D. (Rebecca), Rowe, D.W. (David W.), Loomis, C.A. (Cynthia A.), Evans, D.M. (David M.), Ackert-Bicknell, C.L. (Cheryl), Joyner, A.L. (Alexandra L.), Duncan, E.L. (Emma), Kiel, D.P. (Douglas P.), Rivadeneira Ramirez, F. (Fernando), Richards, J.B. (Brent), Zheng, H.-F. (Hou-Feng), Forgetta, V. (Vincenzo), Hsu, Y.-H. (Yi-Hsiang), Estrada Gil, K. (Karol), Rosello-Diez, A. (Alberto), Leo, P.J. (Paul), Dahia, C.L. (Chitra L.), Park-Min, K.H. (Kyung Hyun), Tobias, J.H. (Jon), Kooperberg, C. (Charles), Kleinman, A. (Aaron), Styrkarsdottir, U. (Unnur), Liu, C.-T. (Ching-Ti), Uggla, C. (Charlotta), Evans, D.S. (Daniel), Nielson, C. (Carrie), Walter, K. (Klaudia), Pettersson-Kymmer, U. (Ulrika), McCarthy, S. (Shane), Eriksson, J. (Joel), Kwan, T. (Tony), Jhamai, M. (Mila), Trajanoska, K. (Katerina), Memari, Y. (Yasin), Min, J.L. (Josine L.), Huang, J. (Jie), Danecek, P. (Petr), Wilmot, B. (Beth), Li, R. (Rui), Chou, W.-C. (Wen-Chi), Mokry, L.E. (Lauren E.), Moayyeri, A. (Alireza), Claussnitzer, M. (Melina), Cheng, C.-H. (Chia-Ho), Cheung, W. (Warren), Medina-Gomez, M.C. (Carolina), Ge, B. (Bing), Chen, S.-H. (Shu-Huang), Choi, K. (Kunho), Oei, L. (Ling), Fraser, J. (James), Kraaij, R. (Robert), Hibbs, M.A. (Matthew A.), Gregson, C.L. (Celia L.), Paquette, D. (Denis), Hofman, A. (Albert), Wibom, C. (Carl), Tranah, G.J. (Gregory), Marshall, M. (Mhairi), Gardiner, B.B. (Brooke B.), Cremin, K. (Katie), Auer, P. (Paul), Hsu, L. (Li), Ring, S. (Susan), Tung, J.Y. (Joyce Y.), Thorleifsson, G. (Gudmar), Enneman, A.W. (Anke), Schoor, N.M. (Natasja) van, Groot, L.C.P.G.M. (Lisette) de, Velde, N. (Nathalie) van der, Melin, B. (Beatrice), Kemp, J.P. (John), Christiansen, C., Sayers, I. (Ian), Zhou, Y. (Yanhua), Calderari, S. (Sophie), Rooij, J.G.J. (Jeroen) van, Carlson, C. (Chris), Peters, U. (Ulrike), Berlivet, S. (Soizik), Dostie, J. (Josée), Uitterlinden, A.G. (André), Williams, S.R. (Stephen R.), Farber, C. (Charles), Grinberg, D. (Daniel), LaCroix, A.Z. (Andrea), Haessler, J. (Jeff), Chasman, D.I. (Daniel), Giulianini, F. (Franco), Rose, L.M. (Lynda M.), Ridker, P.M. (Paul), Eisman, J.A. (John), Nguyen, T.V. (Tuan), Center, J.R. (Jacqueline), Nogues, X. (Xavier), Garcia-Giralt, N. (Natàlia), Launer, L.J. (Lenore), Gudnason, V. (Vilmunder), Mellström, D. (Dan), Vandenput, L. (Liesbeth), Amin, N. (Najaf), Duijn, C.M. (Cornelia) van, Karlsson, M. (Magnus), Ljunggren, O. (Östen), Svensson, O. (Olle), Hallmans, G. (Göran), Rousseau, M.F. (Francois), Giroux, S. (Sylvie), Bussière, J. (Johanne), Arp, P.P. (Pascal), Koromani, F. (Fjorda), Prince, R.L. (Richard L.), Lewis, J.R. (Joshua), Langdahl, B.L. (Bente), Hermann, A.P. (A. Pernille), Jensen, J.-E.B. (Jens-Erik B.), Kaptoge, S. (Stephen), Khaw, K.T., Reeve, J. (Jonathan), Formosa, M.M. (Melissa M.), Xuereb-Anastasi, A. (Angela), Åkesson, K. (Kristina), McGuigan, F.E., Garg, G. (Gaurav), Olmos, D. (David), Zarrabeitia, M.T. (María), Riancho, J.A. (José), Ralston, S.H. (Stuart), Alonso, N. (Nerea), Jiang, X. (Xi), Goltzman, D. (David), Pastinen, T. (Tomi), Grundberg, E. (Elin), Gauguier, D. (Dominique), Orwoll, E.S. (Eric), Karasik, D. (David), Smith, A.V. (Davey), Siggeirsdottir, K. (Kristin), Harris, T.B. (Tamara), Zillikens, M.C. (Carola), Meurs, J.B.J. (Joyce) van, Thorsteinsdottir, U. (Unnur), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Soranzo, N. (Nicole), Durbin, R. (Richard), Wilson, S.G. (Scott), Ntzani, E.E. (Evangelia), Brown, M.A. (Matthew), Zwart, J-A. (John-Anker), Hinds, D.A. (David A.), Spector, T.D. (Timothy), Cupples, L.A. (Adrienne), Ohlsson, C. (Claes), Greenwood, C.M.T. (Celia), Jackson, R.D. (Rebecca), Rowe, D.W. (David W.), Loomis, C.A. (Cynthia A.), Evans, D.M. (David M.), Ackert-Bicknell, C.L. (Cheryl), Joyner, A.L. (Alexandra L.), Duncan, E.L. (Emma), Kiel, D.P. (Douglas P.), Rivadeneira Ramirez, F. (Fernando), and Richards, J.B. (Brent)
Abstract: The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10-14), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10-11; ncases = 98,742 and n controls = 409,511). Using an En1 cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10-11). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation
Published: 2015
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11. Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci

Author: Reppe, S. (Sjur), Wang, Y. (Yunpeng), Thompson, W.K. (Wesley K.), McEvoy, L.K. (Linda K.), Schork, N.J. (Nicholas), Zuber, V. (Verena), Leblanc, M. (Marissa), Bettella, F. (Francesco), Mills, I.G. (Ian G.), Desikan, R.S. (Rahul S.), Djurovic, S. (Srdjan), Gautvik, K.M. (Kaare), Dale, A.M. (Anders), Andreassen, O.A. (Ole), Estrada Gil, K. (Karol), Styrkarsdottir, U. (Unnur), Evangelou, E. (Evangelos), Hsu, Y.-H. (Yi-Hsiang), Duncan, E.L. (Emma), Ntzani, E.E. (Evangelia), Oei, L. (Ling), Albagha, O.M.E. (Omar M.), Amin, N. (Najaf), Kemp, J.P. (John), Koller, D.L. (Daniel), Li, G. (Guo), Liu, C.-T. (Ching-Ti), Minster, R.L. (Ryan), Moayyeri, A. (Alireza), Vandenput, L. (Liesbeth), Willner, D. (Dana), Xiao, S.-M. (Su-Mei), Yerges-Armstrong, L.M. (Laura), Zheng, H.-F. (Hou-Feng), Alonso, N. (Nerea), Eriksson, J. (Joel), Kammerer, C.M. (Candace), Kaptoge, S. (Stephen), Leo, P.J. (Paul), Thorleifsson, G. (Gudmar), Wilson, S.G. (Scott), Wilson, J.F. (James F), Aalto, V. (Ville), Alen, M. (Markku), Aragaki, A.K. (Aaron), Aspelund, T. (Thor), Center, J.R. (Jacqueline), Dailiana, Z. (Zoe), Duggan, C., Garcia, M. (Melissa), Garcia-Giralt, N. (Natàlia), Giroux, S. (Sylvie), Hallmans, G. (Göran), Hocking, L.J. (Lynne), Husted, L.B. (Lise Bjerre), Jameson, K. (Karen), Khusainova, R. (Rita), Kim, G.S. (Ghi Su), Kooperberg, C. (Charles), Koromila, T. (Theodora), Kruk, M. (Marcin), Laaksonen, M. (Marika), Lacroix, A.Z. (Andrea Z.), Lee, S.H. (Seung Hun), Leung, P.C. (Ping C.), Lewis, J.R. (Joshua), Masi, L. (Laura), Mencej-Bedrac, S. (Simona), Nguyen, T.V. (Tuan), Nogues, X. (Xavier), Patel, M.S. (Millan), Prezelj, J. (Janez), Rose, L.M. (Lynda), Scollen, S. (Serena), Siggeirsdottir, K. (Kristin), Smith, A.V. (Davey), Svensson, O. (Olle), Trompet, S. (Stella), Trummer, O. (Olivia), Schoor, N.M. (Natasja) van, Woo, J. (Jean), Zhu, K. (Kun), Balcells, S. (Susana), Brandi, M.L., Buckley, B.M. (Brendan M.), Cheng, S. (Sulin), Christiansen, C., Cooper, C. (Charles), Dedoussis, G.V. (George), Ford, I. (Ian), Frost, M. (Morten), Goltzman, D. (David), González-Macías, J. (Jesús), Kähönen, M. (Mika), Karlsson, M. (Magnus), Khusnutdinova, E.K. (Elza), Koh, J.-M. (Jung-Min), Kollia, P. (Panagoula), Langdahl, B.L. (Bente), Leslie, W.D. (William D.), Lips, P. (Paul), Ljunggren, O. (Östen), Lorenc, R. (Roman), Marc, J. (Janja), Mellström, D. (Dan), Obermayer-Pietsch, B. (Barbara), Olmos, D. (David), Pettersson-Kymmer, U. (Ulrika), Reid, D.M. (David), Riancho, J.A. (José), Ridker, P.M. (Paul), Rousseau, M.F. (Francois), Slagboom, P.E. (Eline), Tang, N.L.S. (Nelson L.S.), Urreizti, R. (Roser), Van Hul, W. (Wim), Viikari, J. (Jorma), Zarrabeitia, M.T. (María), Aulchenko, Y.S. (Yurii), Castaño Betancourt, M.C. (Martha), Grundberg, E. (Elin), Herrera, L. (Lizbeth), Ingvarsson, T. (Torvaldur), Johannsdottir, H. (Hrefna), Kwan, T. (Tony), Li, R. (Rui), Luben, R.N. (Robert), Medina-Gomez, M.C. (Carolina), Palsson, S.T. (Stefan Th), Rotter, J.I. (Jerome I.), Sigurdsson, G. (Gunnar), Meurs, J.B.J. (Joyce) van, Verlaan, D.J. (Dominique), Williams, F.M. (Frances), Wood, A.R. (Andrew), Zhou, Y. (Yanhua), Pastinen, T. (Tomi), Raychaudhuri, S. (Soumya), Cauley, J.A. (Jane), Chasman, D.I. (Daniel), Clark, G.R. (Graeme), Cummings, S.R. (Steven R.), Danoy, P. (Patrick), Dennison, E.M. (Elaine), Eastell, R. (Richard), Eisman, J.A. (John), Gudnason, V. (Vilmundur), Hofman, A. (Albert), Jackson, R.D. (Rebecca), Jones, G. (Graeme), Jukema, J.W. (Jan Wouter), Khaw, K.T., Lehtimäki, T. (Terho), Liu, Y. (YongMei), Lorentzon, M. (Mattias), McCloskey, E.V. (Eugene), Mitchell, B.D. (Braxton), Nandakumar, K. (Kannabiran), Nicholson, G.C. (Geoffrey), Oostra, B.A. (Ben), Peacock, M. (Munro), Pols, H.A.P. (Huib), Prince, R.L. (Richard), Raitakari, O. (Olli), Reid, I.R. (Ian), Robbins, J. (John), Sambrook, P.N. (Philip), Sham, P.C. (Pak Chung), Shuldiner, A.R. (Alan), Tylavsky, F.A. (Frances), Duijn, C.M. (Cornelia) van, Wareham, N.J. (Nicholas J.), Cupples, L.A. (Adrienne), Econs, M.J. (Michael), Evans, D.M. (David), Harris, T.B. (Tamara B.), Kung, A.W.C. (Annie Wai Chee), Psaty, B.M. (Bruce), Reeve, J. (Jonathan), Spector, T.D. (Timothy), Streeten, E.A. (Elizabeth), Zillikens, M.C. (Carola), Thorsteinsdottir, U. (Unnur), Ohlsson, C. (Claes), Karasik, D. (David), Richards, J.B. (Brent), Brown, M.A. (Matthew), Zwart, J-A. (John-Anker), Uitterlinden, A.G. (André), Ralston, S.H. (Stuart), Ioannidis, J.P.A. (John P.A.), Kiel, D.P. (Douglas P.), Rivadeneira Ramirez, F. (Fernando), Reppe, S. (Sjur), Wang, Y. (Yunpeng), Thompson, W.K. (Wesley K.), McEvoy, L.K. (Linda K.), Schork, N.J. (Nicholas), Zuber, V. (Verena), Leblanc, M. (Marissa), Bettella, F. (Francesco), Mills, I.G. (Ian G.), Desikan, R.S. (Rahul S.), Djurovic, S. (Srdjan), Gautvik, K.M. (Kaare), Dale, A.M. (Anders), Andreassen, O.A. (Ole), Estrada Gil, K. (Karol), Styrkarsdottir, U. (Unnur), Evangelou, E. (Evangelos), Hsu, Y.-H. (Yi-Hsiang), Duncan, E.L. (Emma), Ntzani, E.E. (Evangelia), Oei, L. (Ling), Albagha, O.M.E. (Omar M.), Amin, N. (Najaf), Kemp, J.P. (John), Koller, D.L. (Daniel), Li, G. (Guo), Liu, C.-T. (Ching-Ti), Minster, R.L. (Ryan), Moayyeri, A. (Alireza), Vandenput, L. (Liesbeth), Willner, D. (Dana), Xiao, S.-M. (Su-Mei), Yerges-Armstrong, L.M. (Laura), Zheng, H.-F. (Hou-Feng), Alonso, N. (Nerea), Eriksson, J. (Joel), Kammerer, C.M. (Candace), Kaptoge, S. (Stephen), Leo, P.J. (Paul), Thorleifsson, G. (Gudmar), Wilson, S.G. (Scott), Wilson, J.F. (James F), Aalto, V. (Ville), Alen, M. (Markku), Aragaki, A.K. (Aaron), Aspelund, T. (Thor), Center, J.R. (Jacqueline), Dailiana, Z. (Zoe), Duggan, C., Garcia, M. (Melissa), Garcia-Giralt, N. (Natàlia), Giroux, S. (Sylvie), Hallmans, G. (Göran), Hocking, L.J. (Lynne), Husted, L.B. (Lise Bjerre), Jameson, K. (Karen), Khusainova, R. (Rita), Kim, G.S. (Ghi Su), Kooperberg, C. (Charles), Koromila, T. (Theodora), Kruk, M. (Marcin), Laaksonen, M. (Marika), Lacroix, A.Z. (Andrea Z.), Lee, S.H. (Seung Hun), Leung, P.C. (Ping C.), Lewis, J.R. (Joshua), Masi, L. (Laura), Mencej-Bedrac, S. (Simona), Nguyen, T.V. (Tuan), Nogues, X. (Xavier), Patel, M.S. (Millan), Prezelj, J. (Janez), Rose, L.M. (Lynda), Scollen, S. (Serena), Siggeirsdottir, K. (Kristin), Smith, A.V. (Davey), Svensson, O. (Olle), Trompet, S. (Stella), Trummer, O. (Olivia), Schoor, N.M. (Natasja) van, Woo, J. (Jean), Zhu, K. (Kun), Balcells, S. (Susana), Brandi, M.L., Buckley, B.M. (Brendan M.), Cheng, S. (Sulin), Christiansen, C., Cooper, C. (Charles), Dedoussis, G.V. (George), Ford, I. (Ian), Frost, M. (Morten), Goltzman, D. (David), González-Macías, J. (Jesús), Kähönen, M. (Mika), Karlsson, M. (Magnus), Khusnutdinova, E.K. (Elza), Koh, J.-M. (Jung-Min), Kollia, P. (Panagoula), Langdahl, B.L. (Bente), Leslie, W.D. (William D.), Lips, P. (Paul), Ljunggren, O. (Östen), Lorenc, R. (Roman), Marc, J. (Janja), Mellström, D. (Dan), Obermayer-Pietsch, B. (Barbara), Olmos, D. (David), Pettersson-Kymmer, U. (Ulrika), Reid, D.M. (David), Riancho, J.A. (José), Ridker, P.M. (Paul), Rousseau, M.F. (Francois), Slagboom, P.E. (Eline), Tang, N.L.S. (Nelson L.S.), Urreizti, R. (Roser), Van Hul, W. (Wim), Viikari, J. (Jorma), Zarrabeitia, M.T. (María), Aulchenko, Y.S. (Yurii), Castaño Betancourt, M.C. (Martha), Grundberg, E. (Elin), Herrera, L. (Lizbeth), Ingvarsson, T. (Torvaldur), Johannsdottir, H. (Hrefna), Kwan, T. (Tony), Li, R. (Rui), Luben, R.N. (Robert), Medina-Gomez, M.C. (Carolina), Palsson, S.T. (Stefan Th), Rotter, J.I. (Jerome I.), Sigurdsson, G. (Gunnar), Meurs, J.B.J. (Joyce) van, Verlaan, D.J. (Dominique), Williams, F.M. (Frances), Wood, A.R. (Andrew), Zhou, Y. (Yanhua), Pastinen, T. (Tomi), Raychaudhuri, S. (Soumya), Cauley, J.A. (Jane), Chasman, D.I. (Daniel), Clark, G.R. (Graeme), Cummings, S.R. (Steven R.), Danoy, P. (Patrick), Dennison, E.M. (Elaine), Eastell, R. (Richard), Eisman, J.A. (John), Gudnason, V. (Vilmundur), Hofman, A. (Albert), Jackson, R.D. (Rebecca), Jones, G. (Graeme), Jukema, J.W. (Jan Wouter), Khaw, K.T., Lehtimäki, T. (Terho), Liu, Y. (YongMei), Lorentzon, M. (Mattias), McCloskey, E.V. (Eugene), Mitchell, B.D. (Braxton), Nandakumar, K. (Kannabiran), Nicholson, G.C. (Geoffrey), Oostra, B.A. (Ben), Peacock, M. (Munro), Pols, H.A.P. (Huib), Prince, R.L. (Richard), Raitakari, O. (Olli), Reid, I.R. (Ian), Robbins, J. (John), Sambrook, P.N. (Philip), Sham, P.C. (Pak Chung), Shuldiner, A.R. (Alan), Tylavsky, F.A. (Frances), Duijn, C.M. (Cornelia) van, Wareham, N.J. (Nicholas J.), Cupples, L.A. (Adrienne), Econs, M.J. (Michael), Evans, D.M. (David), Harris, T.B. (Tamara B.), Kung, A.W.C. (Annie Wai Chee), Psaty, B.M. (Bruce), Reeve, J. (Jonathan), Spector, T.D. (Timothy), Streeten, E.A. (Elizabeth), Zillikens, M.C. (Carola), Thorsteinsdottir, U. (Unnur), Ohlsson, C. (Claes), Karasik, D. (David), Richards, J.B. (Brent), Brown, M.A. (Matthew), Zwart, J-A. (John-Anker), Uitterlinden, A.G. (André), Ralston, S.H. (Stuart), Ioannidis, J.P.A. (John P.A.), Kiel, D.P. (Douglas P.), and Rivadeneira Ramirez, F. (Fernando)
Abstract: Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity.
Published: 2015
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12. Rare coding variants and X-linked loci associated with age at menarche

Author: Lunetta, K.L. (Kathryn), Day, F.R. (Felix), Sulem, P. (Patrick), Ruth, K.S. (Katherine S.), Tung, J.Y. (Joyce Y.), Hinds, D.A. (David A.), Esko, T. (Tõnu), Elks, C.E. (Cathy), Altmaier, E.L. (Elizabeth), He, C. (Chunyan), Huffman, J.E. (Jennifer), Mihailov, E. (Evelin), Porcu, E. (Eleonora), Robino, A. (Antonietta), Rose, L.M. (Lynda), Schick, U.M. (Ursula), Stolk, L. (Lisette), Teumer, A. (Alexander), Thompson, D. (Deborah), Traglia, M. (Michela), Wang, C.A. (Carol A.), Yerges-Armstrong, L.M. (Laura), Antoniou, A.C. (Antonis), Barbieri, C. (Caterina), Coviello, A.D. (Andrea), Cucca, F. (Francesco), Demerath, E.W. (Ellen), Dunning, A.M. (Alison), Gandin, I. (Ilaria), Grove, M.L. (Megan L.), Gudbjartsson, D.F. (Daniel), Hocking, L.J. (Lynne), Hofman, A. (Albert), Huang, J. (Jian), Jackson, R.D. (Rebecca), Karasik, D. (David), Kriebel, J. (Jennifer), Lange, E.M. (Ethan), Lange, L.A. (Leslie), Langenberg, C. (Claudia), Li, X. (Xin), Luan, J., Mägi, R. (Reedik), Morrison, A.C. (Alanna), Padmanabhan, S. (Sandosh), Pirie, A. (Ailith), Polasek, O. (Ozren), Porteous, D.J. (David J.), Reiner, A. (Alexander), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Sala, C. (Cinzia), Schlessinger, D. (David), Scott, R.A. (Robert), Stöckl, D. (Doris), Visser, J.A. (Jenny), Völker, U. (Uwe), Vozzi, D. (Diego), Wilson, J.G. (James), Zygmunt, M. (Marek), Boerwinkle, E.A. (Eric), Buring, J.E. (Julie), Crisponi, L. (Laura), Easton, D.F. (Douglas), Hayward, C. (Caroline), Hu, F.B. (Frank), Liu, S. (Simin), Metspalu, A. (Andres), Pennell, C.E. (Craig), Ridker, P.M. (Paul), Strauch, K. (Konstantin), Streeten, E.A. (Elizabeth), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Ulivi, S. (Shelia), Völzke, H. (Henry), Wareham, N.J. (Nick), Wellons, M. (Melissa), Franceschini, N. (Nora), Chasman, D.I. (Daniel), Thorsteinsdottir, U. (Unnur), Murray, A. (Anna), Zwart, J-A. (John-Anker), Murabito, J. (Joanne), Ong, K.K. (Ken), Perry, J.R.B. (John), Forouhi, N.G. (Nita G.), Kerrison, N.D. (Nicola D.), Sharp, S.J. (Stephen J.), Sims, M.A. (Matthew), Barroso, I.E. (Inês), Deloukas, P. (Panagiotis), McCarthy, M.I. (Mark), Arriola, L. (Larraitz), Balkau, B. (Beverley), Barricarte, A. (Aurelio), Boeing, H. (Heiner), Franks, P.W., Gonzalez, C. (Carlos), Grioni, S. (Sara), Kaaks, R. (Rudolf), Key, T.J. (Timothy J.), Navarro, C. (Carmen), Nilsson, P.M. (Peter M.), Overvad, K. (Kim), Palli, D. (Domenico), Panico, S. (Salvatore), Quirós, J.R., Rolandsson, O. (Olov), Sacerdote, C. (Carlotta), Sánchez, M.-J. (María-José), Slimani, N. (Nadia), Tjonneland, A. (Anne), Tumino, R. (Rosario), Van Der A, D.L. (Daphne L.), Schouw, Y.T. (Yvonne) van der, Riboli, E. (Elio), Smith, B.H. (Blair), Campbell, A. (Archie), Deary, I.J. (Ian), McIntosh, A.M. (Andrew), Lunetta, K.L. (Kathryn), Day, F.R. (Felix), Sulem, P. (Patrick), Ruth, K.S. (Katherine S.), Tung, J.Y. (Joyce Y.), Hinds, D.A. (David A.), Esko, T. (Tõnu), Elks, C.E. (Cathy), Altmaier, E.L. (Elizabeth), He, C. (Chunyan), Huffman, J.E. (Jennifer), Mihailov, E. (Evelin), Porcu, E. (Eleonora), Robino, A. (Antonietta), Rose, L.M. (Lynda), Schick, U.M. (Ursula), Stolk, L. (Lisette), Teumer, A. (Alexander), Thompson, D. (Deborah), Traglia, M. (Michela), Wang, C.A. (Carol A.), Yerges-Armstrong, L.M. (Laura), Antoniou, A.C. (Antonis), Barbieri, C. (Caterina), Coviello, A.D. (Andrea), Cucca, F. (Francesco), Demerath, E.W. (Ellen), Dunning, A.M. (Alison), Gandin, I. (Ilaria), Grove, M.L. (Megan L.), Gudbjartsson, D.F. (Daniel), Hocking, L.J. (Lynne), Hofman, A. (Albert), Huang, J. (Jian), Jackson, R.D. (Rebecca), Karasik, D. (David), Kriebel, J. (Jennifer), Lange, E.M. (Ethan), Lange, L.A. (Leslie), Langenberg, C. (Claudia), Li, X. (Xin), Luan, J., Mägi, R. (Reedik), Morrison, A.C. (Alanna), Padmanabhan, S. (Sandosh), Pirie, A. (Ailith), Polasek, O. (Ozren), Porteous, D.J. (David J.), Reiner, A. (Alexander), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Sala, C. (Cinzia), Schlessinger, D. (David), Scott, R.A. (Robert), Stöckl, D. (Doris), Visser, J.A. (Jenny), Völker, U. (Uwe), Vozzi, D. (Diego), Wilson, J.G. (James), Zygmunt, M. (Marek), Boerwinkle, E.A. (Eric), Buring, J.E. (Julie), Crisponi, L. (Laura), Easton, D.F. (Douglas), Hayward, C. (Caroline), Hu, F.B. (Frank), Liu, S. (Simin), Metspalu, A. (Andres), Pennell, C.E. (Craig), Ridker, P.M. (Paul), Strauch, K. (Konstantin), Streeten, E.A. (Elizabeth), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Ulivi, S. (Shelia), Völzke, H. (Henry), Wareham, N.J. (Nick), Wellons, M. (Melissa), Franceschini, N. (Nora), Chasman, D.I. (Daniel), Thorsteinsdottir, U. (Unnur), Murray, A. (Anna), Zwart, J-A. (John-Anker), Murabito, J. (Joanne), Ong, K.K. (Ken), Perry, J.R.B. (John), Forouhi, N.G. (Nita G.), Kerrison, N.D. (Nicola D.), Sharp, S.J. (Stephen J.), Sims, M.A. (Matthew), Barroso, I.E. (Inês), Deloukas, P. (Panagiotis), McCarthy, M.I. (Mark), Arriola, L. (Larraitz), Balkau, B. (Beverley), Barricarte, A. (Aurelio), Boeing, H. (Heiner), Franks, P.W., Gonzalez, C. (Carlos), Grioni, S. (Sara), Kaaks, R. (Rudolf), Key, T.J. (Timothy J.), Navarro, C. (Carmen), Nilsson, P.M. (Peter M.), Overvad, K. (Kim), Palli, D. (Domenico), Panico, S. (Salvatore), Quirós, J.R., Rolandsson, O. (Olov), Sacerdote, C. (Carlotta), Sánchez, M.-J. (María-José), Slimani, N. (Nadia), Tjonneland, A. (Anne), Tumino, R. (Rosario), Van Der A, D.L. (Daphne L.), Schouw, Y.T. (Yvonne) van der, Riboli, E. (Elio), Smith, B.H. (Blair), Campbell, A. (Archie), Deary, I.J. (Ian), and McIntosh, A.M. (Andrew)
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; P<5 × 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.
Published: 2015
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13. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche

Author: Perry, J.R.B. (John), Day, F.R. (Felix), Elks, C.E. (Cathy), Sulem, P. (Patrick), Thompson, D. (Deborah), Ferreira, T. (Teresa), He, C. (Chunyan), Chasman, D.I. (Daniel), Esko, T. (Tõnu), Thorleifsson, G. (Gudmar), Albrecht, E. (Eva), Ang, W.Q. (Wei), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Feenstra, B. (Bjarke), Franceschini, N. (Nora), Ganna, A. (Andrea), Johnson, A.D. (Andrew), Kjellqvist, S. (Sanela), Lunetta, K.L. (Kathryn), Mcmahon, G. (George), Nolte, I.M. (Ilja), Paternoster, L. (Lavinia), Porcu, E. (Eleonora), Smith, A.V. (Davey), Stolk, L. (Lisette), Teumer, A. (Alexander), Tsernikova, N. (Natalia), Tikkanen, E. (Emmi), Ulivi, S. (Shelia), Wagner, E.K. (Erin K.), Amin, N. (Najaf), Bierut, L.J. (Laura), Byrne, E.M. (Enda), Hottenga, J.J. (Jouke Jan), Koller, D.L. (Daniel), Mangino, M. (Massimo), Pers, T.H. (Tune), Yerges-Armstrong, L.M. (Laura), Zhao, J.H. (Jing Hua), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Atsma, F. (Femke), Bandinelli, S. (Stefania), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Blomqvist, C. (Carl), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet), Bonnani, B. (Bernardo), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Buring, J.E. (Julie), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, J. (Jinhui), Chenevix-Trench, G. (Georgia), Collée, J.M. (Margriet), Couch, F.J. (Fergus), Couper, D.J. (David), Coviello, A.D. (Andrea), Cox, A. (Angela), Czene, K. (Kamila), Adamo, P. (Pio) d', Vivo, I. (Immaculata) de, Demerath, E.W. (Ellen), Dennis, J. (Joe), Devilee, P. (Peter), Dieffenbach, A.K. (Aida Karina), Dunning, A.M. (Alison), Eiriksdottir, G. (Gudny), Hagen, K. (Knut), Fasching, P.A. (Peter), Ferrucci, L. (Luigi), Flesch-Janys, D. (Dieter), Flyger, H. (Henrik), Foroud, T. (Tatiana), Franke, L. (Lude), Garcia, M. (Melissa), García-Closas, M. (Montserrat), Geller, F. (Frank), Geus, E.J.C. (Eco) de, Giles, G.G. (Graham), Gudbjartsson, D.F. (Daniel), Gudnason, V. (Vilmundur), Guénel, P. (Pascal), Guo, S. (Suiqun), Hall, P. (Per), Hamann, U. (Ute), Haring, R. (Robin), Hartman, C.A. (Catharina), Heath, A.C. (Andrew), Hofman, A. (Albert), Hooning, M.J. (Maartje), Hopper, J.L. (John), Hu, F.B. (Frank), Hunter, D. (David), Karasik, D. (David), Kiel, D.P. (Douglas P.), Knight, J.A. (Julia), Kosma, V-M. (Veli-Matti), Kutalik, Z. (Zoltán), Lai, S. (Sandra), Lambrechts, D. (Diether), Lindblom, A. (Annika), Mägi, R. (Reedik), Magnusson, P.K. (Patrik), Mannermaa, A. (Arto), Martin, N.G. (Nicholas), Masson, G. (Gisli), McArdle, P.F. (Patrick), McArdle, W.L. (Wendy), Melbye, M. (Mads), Michailidou, K. (Kyriaki), Mihailov, E. (Evelin), Milani, L. (Lili), Milne, R.L. (Roger L), Nevanlinna, H. (Heli), Neven, P. (Patrick), Nohr, C. (Christian), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), Palotie, A. (Aarno), Peacock, M. (Munro), Pedersen, N.L. (Nancy L.), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Postma, D.S. (Dirkje), Pouta, A. (Anneli), Pykäs, K. (Katri), Radice, P. (Paolo), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Robino, A. (Antonietta), Rose, L.M. (Lynda), Rudolph, A. (Anja), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (David), Schmidt, M.K. (Marjanka), Southey, M.C. (Mellissa C.), Sovio, U. (Ulla), Stampfer, M.J. (Meir J.), Stöckl, D. (Doris), Storniolo, A.M. (Anna M.), Timpson, N.J. (Nicholas), Tyrer, J.P. (Jonathan), Visser, J.A. (Jenny), Vollenweider, P. (Peter), Völzke, H. (Henry), Waeber, G. (Gérard), Waldenberger, M. (Melanie), Wallaschofski, H. (Henri), Wang, Q. (Qing), Willemsen, G.A.H.M. (Gonneke), Winqvist, R. (Robert), Wolffenbuttel, B.H.R. (Bruce H. R.), Wright, M.J. (Margaret), Boomsma, D.I. (Dorret), Econs, M.J. (Michael), Khaw, K.T., Loos, R.J.F. (Ruth), McCarthy, M.I. (Mark), Montgomery, G.W. (Grant), Rice, J.P. (John), Streeten, E.A. (Elizabeth), Thorsteinsdottir, U. (Unnur), Duijn, C.M. (Cornelia) van, Alizadeh, B.Z. (Behrooz), Bergmann, S.M. (Sven), Boerwinkle, E.A. (Eric), Boyd, H.A. (Heather), Crisponi, L. (Laura), Gasparini, P. (Paolo), Gieger, C. (Christian), Harris, T.B. (Tamara), Ingelsson, E. (Erik), Jarvelin, M.-R. (Marjo-Riitta), Kraft, P. (Peter), Lawlor, D.A. (Debbie), Metspalu, A. (Andres), Pennell, C.E. (Craig), Ridker, P.M. (Paul), Snieder, H. (Harold), Sørensen, T.I.A., Spector, T.D. (Timothy), Strachan, D.P. (David P.), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Widen, E. (Elisabeth), Zygmunt, M. (Marek), Murray, A. (Anna), Easton, D.F. (Douglas), Zwart, J-A. (John-Anker), Murabito, J. (Joanne), Ong, K.K. (Ken K.), Perry, J.R.B. (John), Day, F.R. (Felix), Elks, C.E. (Cathy), Sulem, P. (Patrick), Thompson, D. (Deborah), Ferreira, T. (Teresa), He, C. (Chunyan), Chasman, D.I. (Daniel), Esko, T. (Tõnu), Thorleifsson, G. (Gudmar), Albrecht, E. (Eva), Ang, W.Q. (Wei), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Feenstra, B. (Bjarke), Franceschini, N. (Nora), Ganna, A. (Andrea), Johnson, A.D. (Andrew), Kjellqvist, S. (Sanela), Lunetta, K.L. (Kathryn), Mcmahon, G. (George), Nolte, I.M. (Ilja), Paternoster, L. (Lavinia), Porcu, E. (Eleonora), Smith, A.V. (Davey), Stolk, L. (Lisette), Teumer, A. (Alexander), Tsernikova, N. (Natalia), Tikkanen, E. (Emmi), Ulivi, S. (Shelia), Wagner, E.K. (Erin K.), Amin, N. (Najaf), Bierut, L.J. (Laura), Byrne, E.M. (Enda), Hottenga, J.J. (Jouke Jan), Koller, D.L. (Daniel), Mangino, M. (Massimo), Pers, T.H. (Tune), Yerges-Armstrong, L.M. (Laura), Zhao, J.H. (Jing Hua), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Atsma, F. (Femke), Bandinelli, S. (Stefania), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Blomqvist, C. (Carl), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet), Bonnani, B. (Bernardo), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Buring, J.E. (Julie), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, J. (Jinhui), Chenevix-Trench, G. (Georgia), Collée, J.M. (Margriet), Couch, F.J. (Fergus), Couper, D.J. (David), Coviello, A.D. (Andrea), Cox, A. (Angela), Czene, K. (Kamila), Adamo, P. (Pio) d', Vivo, I. (Immaculata) de, Demerath, E.W. (Ellen), Dennis, J. (Joe), Devilee, P. (Peter), Dieffenbach, A.K. (Aida Karina), Dunning, A.M. (Alison), Eiriksdottir, G. (Gudny), Hagen, K. (Knut), Fasching, P.A. (Peter), Ferrucci, L. (Luigi), Flesch-Janys, D. (Dieter), Flyger, H. (Henrik), Foroud, T. (Tatiana), Franke, L. (Lude), Garcia, M. (Melissa), García-Closas, M. (Montserrat), Geller, F. (Frank), Geus, E.J.C. (Eco) de, Giles, G.G. (Graham), Gudbjartsson, D.F. (Daniel), Gudnason, V. (Vilmundur), Guénel, P. (Pascal), Guo, S. (Suiqun), Hall, P. (Per), Hamann, U. (Ute), Haring, R. (Robin), Hartman, C.A. (Catharina), Heath, A.C. (Andrew), Hofman, A. (Albert), Hooning, M.J. (Maartje), Hopper, J.L. (John), Hu, F.B. (Frank), Hunter, D. (David), Karasik, D. (David), Kiel, D.P. (Douglas P.), Knight, J.A. (Julia), Kosma, V-M. (Veli-Matti), Kutalik, Z. (Zoltán), Lai, S. (Sandra), Lambrechts, D. (Diether), Lindblom, A. (Annika), Mägi, R. (Reedik), Magnusson, P.K. (Patrik), Mannermaa, A. (Arto), Martin, N.G. (Nicholas), Masson, G. (Gisli), McArdle, P.F. (Patrick), McArdle, W.L. (Wendy), Melbye, M. (Mads), Michailidou, K. (Kyriaki), Mihailov, E. (Evelin), Milani, L. (Lili), Milne, R.L. (Roger L), Nevanlinna, H. (Heli), Neven, P. (Patrick), Nohr, C. (Christian), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), Palotie, A. (Aarno), Peacock, M. (Munro), Pedersen, N.L. (Nancy L.), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Postma, D.S. (Dirkje), Pouta, A. (Anneli), Pykäs, K. (Katri), Radice, P. (Paolo), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Robino, A. (Antonietta), Rose, L.M. (Lynda), Rudolph, A. (Anja), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (David), Schmidt, M.K. (Marjanka), Southey, M.C. (Mellissa C.), Sovio, U. (Ulla), Stampfer, M.J. (Meir J.), Stöckl, D. (Doris), Storniolo, A.M. (Anna M.), Timpson, N.J. (Nicholas), Tyrer, J.P. (Jonathan), Visser, J.A. (Jenny), Vollenweider, P. (Peter), Völzke, H. (Henry), Waeber, G. (Gérard), Waldenberger, M. (Melanie), Wallaschofski, H. (Henri), Wang, Q. (Qing), Willemsen, G.A.H.M. (Gonneke), Winqvist, R. (Robert), Wolffenbuttel, B.H.R. (Bruce H. R.), Wright, M.J. (Margaret), Boomsma, D.I. (Dorret), Econs, M.J. (Michael), Khaw, K.T., Loos, R.J.F. (Ruth), McCarthy, M.I. (Mark), Montgomery, G.W. (Grant), Rice, J.P. (John), Streeten, E.A. (Elizabeth), Thorsteinsdottir, U. (Unnur), Duijn, C.M. (Cornelia) van, Alizadeh, B.Z. (Behrooz), Bergmann, S.M. (Sven), Boerwinkle, E.A. (Eric), Boyd, H.A. (Heather), Crisponi, L. (Laura), Gasparini, P. (Paolo), Gieger, C. (Christian), Harris, T.B. (Tamara), Ingelsson, E. (Erik), Jarvelin, M.-R. (Marjo-Riitta), Kraft, P. (Peter), Lawlor, D.A. (Debbie), Metspalu, A. (Andres), Pennell, C.E. (Craig), Ridker, P.M. (Paul), Snieder, H. (Harold), Sørensen, T.I.A., Spector, T.D. (Timothy), Strachan, D.P. (David P.), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Widen, E. (Elisabeth), Zygmunt, M. (Marek), Murray, A. (Anna), Easton, D.F. (Douglas), Zwart, J-A. (John-Anker), Murabito, J. (Joanne), and Ong, K.K. (Ken K.)
Abstract: 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 × 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. Menarc
Published: 2014
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14. Genetic diversity is a predictor of mortality in humans

Author: Bihlmeyer, N.A. (Nathan A.), Brody, J.A. (Jennifer A.), Smith, A.V. (Davey), Lunetta, K.L. (Kathryn), Nalls, M.A. (Michael), Smith, J.A. (Jennifer A), Tanaka, T. (Toshiko), Davies, G. (Gail), Yu, L. (Lei), Mirza, S.S. (Saira), Teumer, A. (Alexander), Coresh, J. (Josef), Pankow, J.S. (James), Franceschini, N. (Nora), Scaria, A. (Anish), Oshima, J. (Junko), Psaty, B.M. (Bruce), Gudnason, V. (Vilmundur), Eiriksdottir, G. (Gudny), Harris, T.B. (Tamara), Li, H. (Hanyue), Karasik, D. (David), Kiel, D.P. (Douglas P.), Garcia, M. (Melissa), Liu, Y. (YongMei), Faul, J.D. (Jessica D.), Kardia, S.L. (Sharon L.r), Zhao, W. (Wei), Ferrucci, L. (Luigi), Allerhand, M.M. (Michael), Liewald, D.C.M. (David), Redmond, P. (Paul), Starr, J.M. (John), Jager, P.L. (Philip) de, Evans, D.A. (Denis), Direk, N. (Nese), Ikram, M.A. (Arfan), Uitterlinden, A.G. (André), Homuth, G. (Georg), Lorbeer, R. (Roberto), Grabe, H.J. (Hans Jörgen), Launer, L.J. (Lenore), Murabito, J. (Joanne), Singleton, A. (Andrew), Weir, D.R. (David), Bandinelli, S. (Stefania), Deary, I.J. (Ian), Bennett, D.A. (David A.), Tiemeier, H.W. (Henning), Kocher, T. (Thomas), Lumley, T. (Thomas), Arking, D.E. (Dan), Bihlmeyer, N.A. (Nathan A.), Brody, J.A. (Jennifer A.), Smith, A.V. (Davey), Lunetta, K.L. (Kathryn), Nalls, M.A. (Michael), Smith, J.A. (Jennifer A), Tanaka, T. (Toshiko), Davies, G. (Gail), Yu, L. (Lei), Mirza, S.S. (Saira), Teumer, A. (Alexander), Coresh, J. (Josef), Pankow, J.S. (James), Franceschini, N. (Nora), Scaria, A. (Anish), Oshima, J. (Junko), Psaty, B.M. (Bruce), Gudnason, V. (Vilmundur), Eiriksdottir, G. (Gudny), Harris, T.B. (Tamara), Li, H. (Hanyue), Karasik, D. (David), Kiel, D.P. (Douglas P.), Garcia, M. (Melissa), Liu, Y. (YongMei), Faul, J.D. (Jessica D.), Kardia, S.L. (Sharon L.r), Zhao, W. (Wei), Ferrucci, L. (Luigi), Allerhand, M.M. (Michael), Liewald, D.C.M. (David), Redmond, P. (Paul), Starr, J.M. (John), Jager, P.L. (Philip) de, Evans, D.A. (Denis), Direk, N. (Nese), Ikram, M.A. (Arfan), Uitterlinden, A.G. (André), Homuth, G. (Georg), Lorbeer, R. (Roberto), Grabe, H.J. (Hans Jörgen), Launer, L.J. (Lenore), Murabito, J. (Joanne), Singleton, A. (Andrew), Weir, D.R. (David), Bandinelli, S. (Stefania), Deary, I.J. (Ian), Bennett, D.A. (David A.), Tiemeier, H.W. (Henning), Kocher, T. (Thomas), Lumley, T. (Thomas), and Arking, D.E. (Dan)
Abstract: BACKGROUND: It has been well-established, both by population genetics theory and direct observation in many organisms, that increased genetic
Published: 2014
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15. A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus

Author: Oei, L. (Ling), Hsu, Y.-H. (Yi-Hsiang), Styrkarsdottir, U. (Unnur), Eussen, H.J.F.M.M. (Bert), Klein, J.E.M.M. (Annelies) de, Peters, M.J. (Marjolein), Halldorsson, B.V. (Bjarni), Liu, C.-T. (Ching-Ti), Alonso, N. (Nerea), Kaptoge, S. (Stephen), Thorleifsson, G. (Gudmar), Hallmans, G. (Göran), Hocking, L.J. (Lynne), Husted, L.B. (Lise Bjerre), Jameson, K. (Karen), Kingdom, M.K. (Marcin KrUnited), Lewis, J.R. (Joshua), Patel, M.S. (Millan), Scollen, S. (Serena), Svensson, O. (Olle), Trompet, S. (Stella), Schoor, N.M. (Natasja) van, Zhu, K. (Kun), Buckley, B.M. (Brendan M.), Cooper, C. (Charles), Ford, I. (Ian), Goltzman, D. (David), González-Macías, J. (Jesús), Langdahl, B.L. (Bente), Leslie, W.D. (William), Lips, P. (Paul), Lorenc, R. (Roman), Olmos, D. (David), Pettersson-Kymmer, U. (Ulrika), Reid, D.M. (David), Riancho, J.A. (José), Slagboom, P.E. (Eline), Garcia-Ibarbia, C. (Carmen), Ingvarsson, T. (Torvaldur), Johannsdottir, H. (Hrefna), Luben, R.N. (Robert), Medina-Gomez, M.C. (Carolina), Arp, P.P. (Pascal), Nandakumar, K. (Kannabiran), Palsson, S.T. (Stefan Th), Sigurdsson, G. (Gunnar), Meurs, J.B.J. (Joyce) van, Zhou, Y. (Yanhua), Hofman, A. (Albert), Jukeme, J.W. (J. Wouter), Pols, H.A.P. (Huib), Prince, R.L. (Richard), Cupples, L.A. (Adrienne), Marshall, C.R. (Christian), Pinto, D. (Duane), Sato, D.K. (DaisUnited Kingdome), Scherer, S.W. (Stephen), Reeve, J. (Jonathan), Thorsteinsdottir, U. (Unnur), Karasik, D. (David), Richards, J.B. (Brent), Zwart, J-A. (John-Anker), Uitterlinden, A.G. (André), Ralston, S.H. (Stuart), Ioannidis, J.P.A. (John), Kiel, D.P. (Douglas), Rivadeneira Ramirez, F. (Fernando), Estrada Gil, K. (Karol), Oei, L. (Ling), Hsu, Y.-H. (Yi-Hsiang), Styrkarsdottir, U. (Unnur), Eussen, H.J.F.M.M. (Bert), Klein, J.E.M.M. (Annelies) de, Peters, M.J. (Marjolein), Halldorsson, B.V. (Bjarni), Liu, C.-T. (Ching-Ti), Alonso, N. (Nerea), Kaptoge, S. (Stephen), Thorleifsson, G. (Gudmar), Hallmans, G. (Göran), Hocking, L.J. (Lynne), Husted, L.B. (Lise Bjerre), Jameson, K. (Karen), Kingdom, M.K. (Marcin KrUnited), Lewis, J.R. (Joshua), Patel, M.S. (Millan), Scollen, S. (Serena), Svensson, O. (Olle), Trompet, S. (Stella), Schoor, N.M. (Natasja) van, Zhu, K. (Kun), Buckley, B.M. (Brendan M.), Cooper, C. (Charles), Ford, I. (Ian), Goltzman, D. (David), González-Macías, J. (Jesús), Langdahl, B.L. (Bente), Leslie, W.D. (William), Lips, P. (Paul), Lorenc, R. (Roman), Olmos, D. (David), Pettersson-Kymmer, U. (Ulrika), Reid, D.M. (David), Riancho, J.A. (José), Slagboom, P.E. (Eline), Garcia-Ibarbia, C. (Carmen), Ingvarsson, T. (Torvaldur), Johannsdottir, H. (Hrefna), Luben, R.N. (Robert), Medina-Gomez, M.C. (Carolina), Arp, P.P. (Pascal), Nandakumar, K. (Kannabiran), Palsson, S.T. (Stefan Th), Sigurdsson, G. (Gunnar), Meurs, J.B.J. (Joyce) van, Zhou, Y. (Yanhua), Hofman, A. (Albert), Jukeme, J.W. (J. Wouter), Pols, H.A.P. (Huib), Prince, R.L. (Richard), Cupples, L.A. (Adrienne), Marshall, C.R. (Christian), Pinto, D. (Duane), Sato, D.K. (DaisUnited Kingdome), Scherer, S.W. (Stephen), Reeve, J. (Jonathan), Thorsteinsdottir, U. (Unnur), Karasik, D. (David), Richards, J.B. (Brent), Zwart, J-A. (John-Anker), Uitterlinden, A.G. (André), Ralston, S.H. (Stuart), Ioannidis, J.P.A. (John), Kiel, D.P. (Douglas), Rivadeneira Ramirez, F. (Fernando), and Estrada Gil, K. (Karol)
Abstract: Background Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk. Aim To identify CNVs associated with osteoporotic bone fracture risk. Method We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies. Results A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10−5). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk. Conclusions These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.
Published: 2014
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16. Association of heat shock proteins with all-cause mortality

Author: Broer, L. (Linda), Demerath, E.W. (Ellen), Garcia, M.E. (M.), Homuth, G. (Georg), Kaplan, R.C. (Robert), Lunetta, K.L. (Kathryn), Tanaka, T. (Toshiko), Tranah, G.J. (Gregory), Walter, S. (S.), Arnold, A.M. (Alice), Atzmon, G. (Gil), Harris, T.B. (Tamara), Hoffmann, W. (Wolfgang), Karasik, D. (David), Kiel, D.P. (Douglas), Kocher, T. (Thomas), Launer, L.J. (Lenore), Lohman, K.K. (K.), Rotter, J.I. (Jerome), Tiemeier, H.W. (Henning), Uitterlinden, A.G. (André), Wallaschofski, H. (Henri), Bandinelli, S. (Stefania), Dorr, M. (Marcus), Ferrucci, L. (Luigi), Franceschini, N. (Nora), Gudnason, V. (Vilmundur), Hofman, A. (Albert), Liu, Y. (YongMei), Murabito, J. (Joanne), Newman, A.B. (Anne), Oostra, B.A. (Ben), Psaty, B.M. (Bruce), Smith, A.V. (Davey), Duijn, C.M. (Cornelia) van, Broer, L. (Linda), Demerath, E.W. (Ellen), Garcia, M.E. (M.), Homuth, G. (Georg), Kaplan, R.C. (Robert), Lunetta, K.L. (Kathryn), Tanaka, T. (Toshiko), Tranah, G.J. (Gregory), Walter, S. (S.), Arnold, A.M. (Alice), Atzmon, G. (Gil), Harris, T.B. (Tamara), Hoffmann, W. (Wolfgang), Karasik, D. (David), Kiel, D.P. (Douglas), Kocher, T. (Thomas), Launer, L.J. (Lenore), Lohman, K.K. (K.), Rotter, J.I. (Jerome), Tiemeier, H.W. (Henning), Uitterlinden, A.G. (André), Wallaschofski, H. (Henri), Bandinelli, S. (Stefania), Dorr, M. (Marcus), Ferrucci, L. (Luigi), Franceschini, N. (Nora), Gudnason, V. (Vilmundur), Hofman, A. (Albert), Liu, Y. (YongMei), Murabito, J. (Joanne), Newman, A.B. (Anne), Oostra, B.A. (Ben), Psaty, B.M. (Bruce), Smith, A.V. (Davey), and Duijn, C.M. (Cornelia) van
Abstract: Experimental mild heat shock is widely known as an intervention that results in extended longevity in various models along the evolutionary lineage. Heat shock proteins (HSPs) are highly upregulated immediately after a heat shock. The elevation in HSP levels was shown to inhibit stress-mediated cell death, and recent experiments indicate a highly versatile role for these proteins as inhibitors of programmed cell death. In this study, we examined common genetic variations in 31 genes encoding all members of the HSP70, small HSP, and heat shock factor (HSF) families for their association with all-cause mortality. Our discovery cohort was the Rotterdam study (RS1) containing 5,974 participants aged 55 years and older (3,174 deaths). We assessed 4,430 single nucleotide polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. After adjusting for multiple testing by permutation analysis, three SNPs showed evidence for association with all-cause mortality in RS1. These findings were followed in eight independent population-based cohorts, leading to a total of 25,007 participants (8,444 deaths). In the replication phase, only HSF2 (rs1416733) remained significantly associated with all-causemortality. Rs1416733 is a known ciseQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality.
Published: 2013
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17. A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple loci implicated in s

Author: Coviello, A.D. (Andrea), Haring, R. (Robin), Wellons, M. (Melissa), Vaidya, D. (Dhananjay), Lehtimäki, T. (Terho), Keildson, S. (Sarah), Lunetta, K.L. (Kathryn), He, C. (Chunyan), Fornage, M. (Myriam), Lagou, V. (Vasiliki), Mangino, M. (Massimo), Onland-Moret, N.C. (Charlotte), Chen, B.H. (Brian), Eriksson, J. (Joel), Garcia, M. (Melissa), Liu, Y. (YongMei), Koster, A. (Annemarie), Lohman, K. (Kurt), Lyytikäinen, L.-P. (Leo-Pekka), Petersen, A.K., Prescott, C.A.J., Stolk, L. (Lisette), Vandenput, L. (Liesbeth), Wood, A.R. (Andrew), Zhuang, W.V., Ruokonen, A. (Aimo), Hartikainen, A.L., Pouta, A. (Anneli), Bandinelli, S. (Stefania), Biffar, R. (Reiner), Brabant, G. (Georg), Cox, D.G. (David), Cummings, S., Ferrucci, L. (Luigi), Gunter, M.J. (Marc J.), Hankinson, S.E. (Susan), Martikainen, H. (Hannu), Hofman, A. (Albert), Homuth, G. (Georg), Illig, T. (Thomas), Jansson, J.O., Johnson, A.D. (Andrew), Karasik, D. (David), Karlsson, M. (Magnus), Kettunen, J. (Johannes), Kiel, D.P. (Douglas), Kraft, P. (Peter), Ljunggren, O. (Östen), Lorentzon, M. (Mattias), Maggio, M. (Marcello), Markus, M.R.P. (Marcello R. P.), Mellström, D. (Dan), Miljkovic, I. (Iva), Mirel, D. (Daniel), Nelson, S. (Sarah), Morin Papunen, L. (Laure), Peeters, P.H.M., Prokopenko, I. (Inga), Raffel, L.J. (Leslie), Reincke, M. (Martin), Reiner, A.P. (Alex), Rexrode, K. (Kathryn), Rivadeneira Ramirez, F. (Fernando), Schwartz, S.M. (Stephen), Siscovick, D.S. (David), Soranzo, N. (Nicole), Stöckl, D. (Doris), Tworoger, S. (Shelley), Uitterlinden, A.G. (André), Gils, C.H. (Carla) van, Vasan, R.S. (Ramachandran Srini), Wichmann, H.E. (Erich), Zhai, G. (Guangju), Bhasin, S. (Shalender), Bidlingmaier, M. (Martin), Chanock, S.J. (Stephen), Vivo, I. (Immaculata) de, Harris, T.B. (Tamara), Hunter, D. (David), Kähönen, M. (Mika), Ouyang, P. (Pamela), Spector, T.D. (Timothy), Schouw, Y.T. (Yvonne) van der, Viikari, J. (Jorma), Wallaschofski, H. (Henri), McCarthy, M.I. (Mark), Frayling, T.M. (Timothy), Murray, J.C. (Jeffrey), Franks, S. (Steve), Jarvelin, M.-R. (Marjo-Riitta), Jong, F.A. (Floris) de, Raitakari, O. (Olli), Teumer, A. (Alexander), Ohlsson, C. (Claes), Murabito, J. (Joanne), Perry, J.R.B. (John), Coviello, A.D. (Andrea), Haring, R. (Robin), Wellons, M. (Melissa), Vaidya, D. (Dhananjay), Lehtimäki, T. (Terho), Keildson, S. (Sarah), Lunetta, K.L. (Kathryn), He, C. (Chunyan), Fornage, M. (Myriam), Lagou, V. (Vasiliki), Mangino, M. (Massimo), Onland-Moret, N.C. (Charlotte), Chen, B.H. (Brian), Eriksson, J. (Joel), Garcia, M. (Melissa), Liu, Y. (YongMei), Koster, A. (Annemarie), Lohman, K. (Kurt), Lyytikäinen, L.-P. (Leo-Pekka), Petersen, A.K., Prescott, C.A.J., Stolk, L. (Lisette), Vandenput, L. (Liesbeth), Wood, A.R. (Andrew), Zhuang, W.V., Ruokonen, A. (Aimo), Hartikainen, A.L., Pouta, A. (Anneli), Bandinelli, S. (Stefania), Biffar, R. (Reiner), Brabant, G. (Georg), Cox, D.G. (David), Cummings, S., Ferrucci, L. (Luigi), Gunter, M.J. (Marc J.), Hankinson, S.E. (Susan), Martikainen, H. (Hannu), Hofman, A. (Albert), Homuth, G. (Georg), Illig, T. (Thomas), Jansson, J.O., Johnson, A.D. (Andrew), Karasik, D. (David), Karlsson, M. (Magnus), Kettunen, J. (Johannes), Kiel, D.P. (Douglas), Kraft, P. (Peter), Ljunggren, O. (Östen), Lorentzon, M. (Mattias), Maggio, M. (Marcello), Markus, M.R.P. (Marcello R. P.), Mellström, D. (Dan), Miljkovic, I. (Iva), Mirel, D. (Daniel), Nelson, S. (Sarah), Morin Papunen, L. (Laure), Peeters, P.H.M., Prokopenko, I. (Inga), Raffel, L.J. (Leslie), Reincke, M. (Martin), Reiner, A.P. (Alex), Rexrode, K. (Kathryn), Rivadeneira Ramirez, F. (Fernando), Schwartz, S.M. (Stephen), Siscovick, D.S. (David), Soranzo, N. (Nicole), Stöckl, D. (Doris), Tworoger, S. (Shelley), Uitterlinden, A.G. (André), Gils, C.H. (Carla) van, Vasan, R.S. (Ramachandran Srini), Wichmann, H.E. (Erich), Zhai, G. (Guangju), Bhasin, S. (Shalender), Bidlingmaier, M. (Martin), Chanock, S.J. (Stephen), Vivo, I. (Immaculata) de, Harris, T.B. (Tamara), Hunter, D. (David), Kähönen, M. (Mika), Ouyang, P. (Pamela), Spector, T.D. (Timothy), Schouw, Y.T. (Yvonne) van der, Viikari, J. (Jorma), Wallaschofski, H. (Henri), McCarthy, M.I. (Mark), Frayling, T.M. (Timothy), Murray, J.C. (Jeffrey), Franks, S. (Steve), Jarvelin, M.-R. (Marjo-Riitta), Jong, F.A. (Floris) de, Raitakari, O. (Olli), Teumer, A. (Alexander), Ohlsson, C. (Claes), Murabito, J. (Joanne), and Perry, J.R.B. (John)
Abstract: Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG, PRMT6, GCKR, ZBTB10, JMJD1C, SLCO1B1, NR2F2, ZNF652, TDGF3, LHCGR, BAIAP2L1, and UGT2B15. These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only. Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ~15.6% and ~8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
Published: 2012
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18. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Author: Estrada Gil, K. (Karol), Styrkarsdottir, U. (Unnur), Evangelou, E. (Evangelos), Hsu, Y.-H. (Yi-Hsiang), Duncan, E.L. (Emma), Ntzani, E.E. (Evangelia), Oei, L. (Ling), Albagha, O.M.E. (Omar M.), Amin, N. (Najaf), Kemp, J.P. (John), Koller, D.L. (Daniel), Li, G. (Guo), Liu, C.-T. (Ching-Ti), Minster, R.L. (Ryan), Moayyeri, A. (Alireza), Vandenput, L. (Liesbeth), Willner, D. (Dana), Xiao, S.-M. (Su-Mei), Yerges-Armstrong, L.M. (Laura), Zheng, H.-F. (Hou-Feng), Alonso, N. (Nerea), Eriksson, J. (Joel), Kammerer, C.M. (Candace), Kaptoge, S. (Stephen), Leo, P.J. (Paul), Thorleifsson, G. (Gudmar), Wilson, S.G. (Scott), Wilson, J.F. (James), Aalto, V. (Ville), Alen, T.A. (Theo) van, Aragaki, A.K. (Aaron), Aspelund, T. (Thor), Center, J.R. (Jacqueline), Dailiana, Z. (Zoe), Duggan, C., Garcia, M. (Melissa), Garcia-Giralt, N. (Natàlia), Giroux, S. (Sylvie), Hallmans, G. (Göran), Hocking, L.J. (Lynne), Husted, L.B. (Lise Bjerre), Jameson, K. (Karen), Khusainova, R. (Rita), Kim, G.S. (Ghi Su), Kooperberg, C. (Charles), Koromila, T. (Theodora), Kruk, M. (Marcin), Laaksonen, M. (Marika), LaCroix, A.Z. (Andrea), Lee, S.U. (Seung), Leung, P.C. (Ping), Lewis, J.R. (Joshua), Masi, L. (Laura), Mencej-Bedrac, S. (Simona), Nguyen, T.V. (Tuan), Nogues, X. (Xavier), Patel, M.S. (Millan), Prezelj, J. (Janez), Rose, L.M. (Lynda), Scollen, S. (Serena), Siggeirsdottir, K. (Kristin), Smith, A.V. (Davey), Svensson, O. (Olle), Trompet, S. (Stella), Trummer, O. (Olivia), Schoor, N.M. (Natasja) van, Woo, M.M. (Margaret M.), Zhu, K. (Kun), Balcells, S. (Susana), Brandi, M.L., Buckley, B.M. (Brendan M.), Cheng, S. (Sulin), Christiansen, C., Cooper, C. (Charles), Dedoussis, G.V. (George), Ford, I. (Ian), Frost, M. (Morten), Goltzman, D. (David), González-Macías, J. (Jesús), Kähönen, M. (Mika), Karlsson, M. (Magnus), Khusnutdinova, E.K. (Elza), Koh, J.-M. (Jung-Min), Kollia, P. (Panagoula), Langdahl, B.L. (Bente), Leslie, W.D. (William), Lips, P. (Paul), Ljunggren, O. (Östen), Lorenc, R. (Roman), Marc, J. (Janja), Mellström, D. (Dan), Obermayer-Pietsch, B. (Barbara), Olmos, D. (David), Pettersson-Kymmer, U. (Ulrika), Reid, D.M. (David), Riancho, J.A. (José), Ridker, P.M. (Paul), Rousseau, M.F. (Francois), Slagboom, P.E. (Eline), Tang, N.L.S. (Nelson L.), Urreizti, R. (Roser), Van Hul, W. (Wim), Viikari, J. (Jorma), Zarrabeitia, M.T. (María), Aulchenko, Y.S. (Yurii), Castaño Betancourt, M.C. (Martha), Grundberg, E. (Elin), Herrera, L. (Lizbeth), Ingvarsson, T. (Torvaldur), Johannsdottir, H. (Hrefna), Kwan, T. (Tony), Li, R. (Rui), Luben, R.N. (Robert), Medina-Gomez, M.C. (Carolina), Palsson, S.T. (Stefan), Reppe, S. (Sjur), Rotter, J.I. (Jerome), Sigurdsson, G. (Gunnar), Meurs, J.B.J. (Joyce) van, Verlaan, D.J. (Dominique), Williams, F.M. (Frances), Wood, A.R. (Andrew), Zhou, Y. (Yanhua), Gautvik, K.M. (Kaare), Pastinen, T. (Tomi), Raychaudhuri, S. (Soumya), Cauley, J.A. (Jane), Chasman, D.I. (Daniel), Clark, G.R. (Graeme), Cummings, S., Danoy, P. (Patrick), Dennison, E.M. (Elaine), Eastell, R. (Richard), Eisman, J.A. (John), Gudnason, V. (Vilmundur), Hofman, A. (Albert), Jackson, R.D. (Rebecca), Jones, G. (Graeme), Jukema, J.W. (Jan Wouter), Khaw, K-T. (Kay-Tee), Lehtimäki, T. (Terho), Liu, Y. (YongMei), Lorentzon, M. (Mattias), McCloskey, E.V. (Eugene), Mitchell, B.D. (Braxton), Nandakumar, K. (Kannabiran), Nicholson, G.C. (Geoffrey), Oostra, B.A. (Ben), Peacock, M. (Munro), Pols, H.A.P. (Huib), Prince, R.L. (Richard), Raitakari, O. (Olli), Reid, I.R. (Ian), Robbins, J. (John), Sambrook, P.N. (Philip), Sham, P.C. (Pak), Shuldiner, A.R. (Alan), Tylavsky, F.A. (Frances), Duijn, C.M. (Cornelia) van, Wareham, N.J. (Nick), Cupples, L.A. (Adrienne), Econs, M.J. (Michael), Evans, D.M. (David), Harris, T.B. (Tamara), Kung, A.W.C. (Annie), Psaty, B.M. (Bruce), Reeve, J. (Jonathan), Spector, T.D. (Timothy), Streeten, E.A. (Elizabeth), Zillikens, M.C. (Carola), Thorsteinsdottir, U. (Unnur), Ohlsson, C. (Claes), Karasik, D. (David), Richards, J.B. (Brent), Brown, M.A. (Matthew), Zwart, J-A. (John-Anker), Uitterlinden, A.G. (André), Ralston, S.H. (Stuart), Ioannidis, J.P.A. (John), Kiel, D.P. (Douglas), Rivadeneira Ramirez, F. (Fernando), Estrada Gil, K. (Karol), Styrkarsdottir, U. (Unnur), Evangelou, E. (Evangelos), Hsu, Y.-H. (Yi-Hsiang), Duncan, E.L. (Emma), Ntzani, E.E. (Evangelia), Oei, L. (Ling), Albagha, O.M.E. (Omar M.), Amin, N. (Najaf), Kemp, J.P. (John), Koller, D.L. (Daniel), Li, G. (Guo), Liu, C.-T. (Ching-Ti), Minster, R.L. (Ryan), Moayyeri, A. (Alireza), Vandenput, L. (Liesbeth), Willner, D. (Dana), Xiao, S.-M. (Su-Mei), Yerges-Armstrong, L.M. (Laura), Zheng, H.-F. (Hou-Feng), Alonso, N. (Nerea), Eriksson, J. (Joel), Kammerer, C.M. (Candace), Kaptoge, S. (Stephen), Leo, P.J. (Paul), Thorleifsson, G. (Gudmar), Wilson, S.G. (Scott), Wilson, J.F. (James), Aalto, V. (Ville), Alen, T.A. (Theo) van, Aragaki, A.K. (Aaron), Aspelund, T. (Thor), Center, J.R. (Jacqueline), Dailiana, Z. (Zoe), Duggan, C., Garcia, M. (Melissa), Garcia-Giralt, N. (Natàlia), Giroux, S. (Sylvie), Hallmans, G. (Göran), Hocking, L.J. (Lynne), Husted, L.B. (Lise Bjerre), Jameson, K. (Karen), Khusainova, R. (Rita), Kim, G.S. (Ghi Su), Kooperberg, C. (Charles), Koromila, T. (Theodora), Kruk, M. (Marcin), Laaksonen, M. (Marika), LaCroix, A.Z. (Andrea), Lee, S.U. (Seung), Leung, P.C. (Ping), Lewis, J.R. (Joshua), Masi, L. (Laura), Mencej-Bedrac, S. (Simona), Nguyen, T.V. (Tuan), Nogues, X. (Xavier), Patel, M.S. (Millan), Prezelj, J. (Janez), Rose, L.M. (Lynda), Scollen, S. (Serena), Siggeirsdottir, K. (Kristin), Smith, A.V. (Davey), Svensson, O. (Olle), Trompet, S. (Stella), Trummer, O. (Olivia), Schoor, N.M. (Natasja) van, Woo, M.M. (Margaret M.), Zhu, K. (Kun), Balcells, S. (Susana), Brandi, M.L., Buckley, B.M. (Brendan M.), Cheng, S. (Sulin), Christiansen, C., Cooper, C. (Charles), Dedoussis, G.V. (George), Ford, I. (Ian), Frost, M. (Morten), Goltzman, D. (David), González-Macías, J. (Jesús), Kähönen, M. (Mika), Karlsson, M. (Magnus), Khusnutdinova, E.K. (Elza), Koh, J.-M. (Jung-Min), Kollia, P. (Panagoula), Langdahl, B.L. (Bente), Leslie, W.D. (William), Lips, P. (Paul), Ljunggren, O. (Östen), Lorenc, R. (Roman), Marc, J. (Janja), Mellström, D. (Dan), Obermayer-Pietsch, B. (Barbara), Olmos, D. (David), Pettersson-Kymmer, U. (Ulrika), Reid, D.M. (David), Riancho, J.A. (José), Ridker, P.M. (Paul), Rousseau, M.F. (Francois), Slagboom, P.E. (Eline), Tang, N.L.S. (Nelson L.), Urreizti, R. (Roser), Van Hul, W. (Wim), Viikari, J. (Jorma), Zarrabeitia, M.T. (María), Aulchenko, Y.S. (Yurii), Castaño Betancourt, M.C. (Martha), Grundberg, E. (Elin), Herrera, L. (Lizbeth), Ingvarsson, T. (Torvaldur), Johannsdottir, H. (Hrefna), Kwan, T. (Tony), Li, R. (Rui), Luben, R.N. (Robert), Medina-Gomez, M.C. (Carolina), Palsson, S.T. (Stefan), Reppe, S. (Sjur), Rotter, J.I. (Jerome), Sigurdsson, G. (Gunnar), Meurs, J.B.J. (Joyce) van, Verlaan, D.J. (Dominique), Williams, F.M. (Frances), Wood, A.R. (Andrew), Zhou, Y. (Yanhua), Gautvik, K.M. (Kaare), Pastinen, T. (Tomi), Raychaudhuri, S. (Soumya), Cauley, J.A. (Jane), Chasman, D.I. (Daniel), Clark, G.R. (Graeme), Cummings, S., Danoy, P. (Patrick), Dennison, E.M. (Elaine), Eastell, R. (Richard), Eisman, J.A. (John), Gudnason, V. (Vilmundur), Hofman, A. (Albert), Jackson, R.D. (Rebecca), Jones, G. (Graeme), Jukema, J.W. (Jan Wouter), Khaw, K-T. (Kay-Tee), Lehtimäki, T. (Terho), Liu, Y. (YongMei), Lorentzon, M. (Mattias), McCloskey, E.V. (Eugene), Mitchell, B.D. (Braxton), Nandakumar, K. (Kannabiran), Nicholson, G.C. (Geoffrey), Oostra, B.A. (Ben), Peacock, M. (Munro), Pols, H.A.P. (Huib), Prince, R.L. (Richard), Raitakari, O. (Olli), Reid, I.R. (Ian), Robbins, J. (John), Sambrook, P.N. (Philip), Sham, P.C. (Pak), Shuldiner, A.R. (Alan), Tylavsky, F.A. (Frances), Duijn, C.M. (Cornelia) van, Wareham, N.J. (Nick), Cupples, L.A. (Adrienne), Econs, M.J. (Michael), Evans, D.M. (David), Harris, T.B. (Tamara), Kung, A.W.C. (Annie), Psaty, B.M. (Bruce), Reeve, J. (Jonathan), Spector, T.D. (Timothy), Streeten, E.A. (Elizabeth), Zillikens, M.C. (Carola), Thorsteinsdottir, U. (Unnur), Ohlsson, C. (Claes), Karasik, D. (David), Richards, J.B. (Brent), Brown, M.A. (Matthew), Zwart, J-A. (John-Anker), Uitterlinden, A.G. (André), Ralston, S.H. (Stuart), Ioannidis, J.P.A. (John), Kiel, D.P. (Douglas), and Rivadeneira Ramirez, F. (Fernando)
Abstract: Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10 -8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10 -4, Bonferroni corrected), of which six reached P < 5 × 10 -8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Published: 2012
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19. A genome-wide association study of aging

Author: Walter, S. (Stefan), Atzmon, G. (Gil), Demerath, E.W. (Ellen), Garcia, M. (Melissa), Kaplan, R.C. (Robert), Kumari, M. (Meena), Lunetta, K.L. (Kathryn), Milaneschi, Y. (Yuri), Tanaka, T. (Toshiko), Tranah, G.J. (Gregory), Völker, U. (Uwe), Yu, L. (Lei), Arnold, A.M. (Alice), Benjamin, E.J. (Emelia), Biffar, R. (Reiner), Buchman, A.S. (Aron), Boerwinkle, E.A. (Eric), Couper, D. (David), Jager, P.L. (Philip) de, Evans, D.A. (Denis), Harris, T.B. (Tamara), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Karasik, D. (David), Kiel, D.P. (Douglas), Kocher, T. (Thomas), Kuningas, M. (Maris), Launer, L.J. (Lenore), Lohman, K. (Kurt), Lutsey, P.L. (Pamela), Mackenbach, J.P. (Johan), Marciante, K. (Kristin), Psaty, B.M. (Bruce), Reiman, E.M. (Eric), Rotter, J.I. (Jerome), Seshadri, S. (Sudha), Shardell, M.D. (Michelle), Smith, A.V. (Albert Vernon), Tikka-Kleemola, P. (Päivi), Walston, J. (Jeremy), Zillikens, M.C. (Carola), Bandinelli, S. (Stefania), Baumeister, S.E. (Sebastian), Bennett, D.A. (David), Ferrucci, L. (Luigi), Gudnason, V. (Vilmundur), Kivimaki, M. (Mika), Liu, Y. (YongMei), Murabito, J. (Joanne), Newman, A.B. (Anne), Tiemeier, H.W. (Henning), Franceschini, N. (Nora), Walter, S. (Stefan), Atzmon, G. (Gil), Demerath, E.W. (Ellen), Garcia, M. (Melissa), Kaplan, R.C. (Robert), Kumari, M. (Meena), Lunetta, K.L. (Kathryn), Milaneschi, Y. (Yuri), Tanaka, T. (Toshiko), Tranah, G.J. (Gregory), Völker, U. (Uwe), Yu, L. (Lei), Arnold, A.M. (Alice), Benjamin, E.J. (Emelia), Biffar, R. (Reiner), Buchman, A.S. (Aron), Boerwinkle, E.A. (Eric), Couper, D. (David), Jager, P.L. (Philip) de, Evans, D.A. (Denis), Harris, T.B. (Tamara), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Karasik, D. (David), Kiel, D.P. (Douglas), Kocher, T. (Thomas), Kuningas, M. (Maris), Launer, L.J. (Lenore), Lohman, K. (Kurt), Lutsey, P.L. (Pamela), Mackenbach, J.P. (Johan), Marciante, K. (Kristin), Psaty, B.M. (Bruce), Reiman, E.M. (Eric), Rotter, J.I. (Jerome), Seshadri, S. (Sudha), Shardell, M.D. (Michelle), Smith, A.V. (Albert Vernon), Tikka-Kleemola, P. (Päivi), Walston, J. (Jeremy), Zillikens, M.C. (Carola), Bandinelli, S. (Stefania), Baumeister, S.E. (Sebastian), Bennett, D.A. (David), Ferrucci, L. (Luigi), Gudnason, V. (Vilmundur), Kivimaki, M. (Mika), Liu, Y. (YongMei), Murabito, J. (Joanne), Newman, A.B. (Anne), Tiemeier, H.W. (Henning), and Franceschini, N. (Nora)
Abstract: Human longevity and healthy aging show moderate heritability (20%-50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10-8). We found 14 independent SNPs that predicted risk of death, and 8 SNPs that predicted event-free survival (p < 10-5). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer's disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity.
Published: 2011
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20. Large common deletions associate with mortality at old age

Author: Kuningas, M. (Maris), Estrada Gil, K. (Karol), Hsu, Y.-H. (Yi-Hsiang), Nandakumar, K. (Kannabiran), Uitterlinden, A.G. (André), Lunetta, K.L. (Kathryn), Tikka-Kleemola, P. (Päivi), Karasik, D. (David), Hofman, A. (Albert), Murabito, J. (Joanne), Rivadeneira Ramirez, F. (Fernando), Kiel, D.P. (Douglas), Tiemeier, H.W. (Henning), Kuningas, M. (Maris), Estrada Gil, K. (Karol), Hsu, Y.-H. (Yi-Hsiang), Nandakumar, K. (Kannabiran), Uitterlinden, A.G. (André), Lunetta, K.L. (Kathryn), Tikka-Kleemola, P. (Päivi), Karasik, D. (David), Hofman, A. (Albert), Murabito, J. (Joanne), Rivadeneira Ramirez, F. (Fernando), Kiel, D.P. (Douglas), and Tiemeier, H.W. (Henning)
Abstract: Copy-number variants (CNVs) are a source of genetic variation that increasingly are associated with human disease. However, the role of CNVs in human lifespan is to date unknown. To identify CNVs that influence mortality at old age, we analyzed genome-wide CNV data in 5178 participants of Rotterdam Study (RS1) and positive findings were evaluated in 1714 participants of the second cohort of the Rotterdam Study (RS2) and in 4550 participants of Framingham Heart Study (FHS). First, we assessed the total burden of rare (frequency <1%) and common (frequency >1%) CNVs for association with mortality during follow-up. These analyses were repeated by stratifying CNVs by type and size. Secondly, we assessed individual comm
Published: 2011
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21. Genetic determinants of serum testosterone concentrations in men

Author: Ohlsson, C. (Claes), Wallaschofski, H. (Henri), Lunetta, K.L. (Kathryn), Stolk, L. (Lisette), Perry, J.R.B. (John), Koster, A. (Annemarie), Petersen, A.K., Eriksson, J. (Joel), Lehtimäki, T. (Terho), Huhtaniemi, I.T. (Ilpo), Hammond, G.L. (Geoffrey), Maggio, M. (Marcello), Coviello, A.D. (Andrea), Ferrucci, L. (Luigi), Heier, M. (Margit), Hofman, A. (Albert), Holliday, K.L. (Kate), Jansson, J.O., Kähönen, M. (Mika), Karasik, D. (David), Karlsson, M.K. (Magnus), Kiel, D.P. (Douglas), Liu, Y. (YongMei), Ljunggren, Ö., Lorentzon, M. (Mattias), Lyytikäinen, L.-P. (Leo-Pekka), Meitinger, T. (Thomas), Mellström, D. (Dan), Melzer, D. (David), Miljkovic, I. (Iva), Nauck, M. (Matthias), Nilsson, M. (Maria), Penninx, B.W.J.H. (Brenda), Pye, S.R. (Stephen), Vasan, R.S. (Ramachandran Srini), Reincke, M. (Martin), Rivadeneira Ramirez, F. (Fernando), Tajar, A. (Abdelouahid), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Ulloor, J. (Jagadish), Viikari, J. (Jorma), Völker, U. (Uwe), Völzke, H. (Henry), Wichmann, H.E. (Heinz Erich), Wu, T.-S., Zhuang, W.V., Ziv, E. (Elad), Raitakari, O. (Olli), Bidlingmaier, M. (Martin), Harris, T.B. (Tamara), Murray, A. (Anna), Jong, F.H. (Frank) de, Murabito, J. (Joanne), Bhasin, S. (Shalender), Vandenput, L. (Liesbeth), Haring, R. (Robin), Ohlsson, C. (Claes), Wallaschofski, H. (Henri), Lunetta, K.L. (Kathryn), Stolk, L. (Lisette), Perry, J.R.B. (John), Koster, A. (Annemarie), Petersen, A.K., Eriksson, J. (Joel), Lehtimäki, T. (Terho), Huhtaniemi, I.T. (Ilpo), Hammond, G.L. (Geoffrey), Maggio, M. (Marcello), Coviello, A.D. (Andrea), Ferrucci, L. (Luigi), Heier, M. (Margit), Hofman, A. (Albert), Holliday, K.L. (Kate), Jansson, J.O., Kähönen, M. (Mika), Karasik, D. (David), Karlsson, M.K. (Magnus), Kiel, D.P. (Douglas), Liu, Y. (YongMei), Ljunggren, Ö., Lorentzon, M. (Mattias), Lyytikäinen, L.-P. (Leo-Pekka), Meitinger, T. (Thomas), Mellström, D. (Dan), Melzer, D. (David), Miljkovic, I. (Iva), Nauck, M. (Matthias), Nilsson, M. (Maria), Penninx, B.W.J.H. (Brenda), Pye, S.R. (Stephen), Vasan, R.S. (Ramachandran Srini), Reincke, M. (Martin), Rivadeneira Ramirez, F. (Fernando), Tajar, A. (Abdelouahid), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Ulloor, J. (Jagadish), Viikari, J. (Jorma), Völker, U. (Uwe), Völzke, H. (Henry), Wichmann, H.E. (Heinz Erich), Wu, T.-S., Zhuang, W.V., Ziv, E. (Elad), Raitakari, O. (Olli), Bidlingmaier, M. (Martin), Harris, T.B. (Tamara), Murray, A. (Anna), Jong, F.H. (Frank) de, Murabito, J. (Joanne), Bhasin, S. (Shalender), Vandenput, L. (Liesbeth), and Haring, R. (Robin)
Abstract: Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10-41and rs6258, p = 2.3×10-22). Subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10-16). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.
Published: 2011
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22. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile

Author: Kilpeläinen, T.O. (Tuomas), Zillikens, M.C. (Carola), Stancáková, A. (Alena), Finucane, F.M. (Francis), Ried, J.S. (Janina), Langenberg, C. (Claudia), Zhang, W. (Weihua), Beckmann, J.S. (Jacques), Luan, J., Vandenput, L. (Liesbeth), Styrkarsdottir, U. (Unnur), Zhou, Y. (Yanhua), Smith, A.V. (Albert Vernon), Zhao, J.H. (Jing Hua), Amin, N. (Najaf), Vedantam, S. (Sailaja), Shin, S.-Y., Haritunians, T. (Talin), Fu, M. (Mao), Feitosa, M.F. (Mary Furlan), Kumari, M. (Meena), Halldorsson, B.V. (Bjarni), Tikkanen, E. (Emmi), Mangino, M. (Massimo), Hayward, C. (Caroline), Song, C. (Ci), Arnold, A.M. (Alice), Oostra, B.A. (Ben), Campbell, H. (Harry), Cupples, L.A. (Adrienne), Davis, K.E. (Kathryn), Döring, A. (Angela), Eiriksdottir, G. (Gudny), Estrada Gil, K. (Karol), Fernández-Real, J.M., Garcia, M. (Melissa), Gieger, C. (Christian), Glazer, N.L. (Nicole), Guiducci, C. (Candace), Hofman, A. (Albert), Humphries, S.E. (Steve), Isomaa, B. (Bo), Jacobs, L.C. (Leonie), Jula, A. (Antti), Karasik, D. (David), Karlsson, M.K. (Magnus), Khaw, K-T. (Kay-Tee), Kim, L.J. (Lauren), Kivimaki, M. (Mika), Klopp, N. (Norman), Kuhnel, B. (Brigitte), Kuusisto, J. (Johanna), Liu, Y. (YongMei), Ljunggren, Ö., Lorentzon, M. (Mattias), Luben, R.N. (Robert), McKnight, B. (Barbara), Mellström, D. (Dan), Mitchell, B.D. (Braxton), Mooser, V. (Vincent), Moreno, J.M., Männistö, S. (Satu), O'Connell, J.R. (Jeffery), Pascoe, L. (Laura), Peltonen, L. (Leena Johanna), Peral, B. (Belén), Perola, M. (Markus), Psaty, B.M. (Bruce), Salomaa, V. (Veikko), Savage, D.B. (David), Semple, R.K. (Robert), Skaric-Juric, T. (Tatjana), Sigurdsson, G. (Gunnar), Spector, T.D. (Timothy), Syvänen, A.-C., Talmud, P.J. (Philippa), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Vidal-Puig, A. (Antonio), Wild, S.H. (Sarah), Wright, A.F. (Alan), Clegg, D.J. (Deborah), Schadt, E.E. (Eric), Wilson, J.F. (James), Rudan, I. (Igor), Ripatti, S. (Samuli), Borecki, I.B. (Ingrid), Shuldiner, A.R. (Alan), Ingelsson, E. (Erik), Jansson, J.O., Kaplan, R.C. (Robert), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Groop, L. (Leif), Kiel, D.P. (Douglas), Rivadeneira Ramirez, F. (Fernando), Walker, M. (Mark), Barroso, I.E. (Inês), Vollenweider, P. (Peter), Waeber, G. (Gérard), Chambers, J.C. (John), Kooner, J.S. (Jaspal), Soranzo, N. (Nicole), Hirschhorn, J.N. (Joel), Stefansson, K. (Kari), Wichmann, H.E. (Heinz Erich), Ohlsson, C. (Claes), O'Rahilly, S. (Stephen), Wareham, N.J. (Nick), Speliotes, E.K. (Elizabeth), Fox, C.S. (Caroline), Laakso, M. (Markku), Loos, R.J.F. (Ruth), Aulchenko, Y.S. (Yurii), Kilpeläinen, T.O. (Tuomas), Zillikens, M.C. (Carola), Stancáková, A. (Alena), Finucane, F.M. (Francis), Ried, J.S. (Janina), Langenberg, C. (Claudia), Zhang, W. (Weihua), Beckmann, J.S. (Jacques), Luan, J., Vandenput, L. (Liesbeth), Styrkarsdottir, U. (Unnur), Zhou, Y. (Yanhua), Smith, A.V. (Albert Vernon), Zhao, J.H. (Jing Hua), Amin, N. (Najaf), Vedantam, S. (Sailaja), Shin, S.-Y., Haritunians, T. (Talin), Fu, M. (Mao), Feitosa, M.F. (Mary Furlan), Kumari, M. (Meena), Halldorsson, B.V. (Bjarni), Tikkanen, E. (Emmi), Mangino, M. (Massimo), Hayward, C. (Caroline), Song, C. (Ci), Arnold, A.M. (Alice), Oostra, B.A. (Ben), Campbell, H. (Harry), Cupples, L.A. (Adrienne), Davis, K.E. (Kathryn), Döring, A. (Angela), Eiriksdottir, G. (Gudny), Estrada Gil, K. (Karol), Fernández-Real, J.M., Garcia, M. (Melissa), Gieger, C. (Christian), Glazer, N.L. (Nicole), Guiducci, C. (Candace), Hofman, A. (Albert), Humphries, S.E. (Steve), Isomaa, B. (Bo), Jacobs, L.C. (Leonie), Jula, A. (Antti), Karasik, D. (David), Karlsson, M.K. (Magnus), Khaw, K-T. (Kay-Tee), Kim, L.J. (Lauren), Kivimaki, M. (Mika), Klopp, N. (Norman), Kuhnel, B. (Brigitte), Kuusisto, J. (Johanna), Liu, Y. (YongMei), Ljunggren, Ö., Lorentzon, M. (Mattias), Luben, R.N. (Robert), McKnight, B. (Barbara), Mellström, D. (Dan), Mitchell, B.D. (Braxton), Mooser, V. (Vincent), Moreno, J.M., Männistö, S. (Satu), O'Connell, J.R. (Jeffery), Pascoe, L. (Laura), Peltonen, L. (Leena Johanna), Peral, B. (Belén), Perola, M. (Markus), Psaty, B.M. (Bruce), Salomaa, V. (Veikko), Savage, D.B. (David), Semple, R.K. (Robert), Skaric-Juric, T. (Tatjana), Sigurdsson, G. (Gunnar), Spector, T.D. (Timothy), Syvänen, A.-C., Talmud, P.J. (Philippa), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Vidal-Puig, A. (Antonio), Wild, S.H. (Sarah), Wright, A.F. (Alan), Clegg, D.J. (Deborah), Schadt, E.E. (Eric), Wilson, J.F. (James), Rudan, I. (Igor), Ripatti, S. (Samuli), Borecki, I.B. (Ingrid), Shuldiner, A.R. (Alan), Ingelsson, E. (Erik), Jansson, J.O., Kaplan, R.C. (Robert), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Groop, L. (Leif), Kiel, D.P. (Douglas), Rivadeneira Ramirez, F. (Fernando), Walker, M. (Mark), Barroso, I.E. (Inês), Vollenweider, P. (Peter), Waeber, G. (Gérard), Chambers, J.C. (John), Kooner, J.S. (Jaspal), Soranzo, N. (Nicole), Hirschhorn, J.N. (Joel), Stefansson, K. (Kari), Wichmann, H.E. (Heinz Erich), Ohlsson, C. (Claes), O'Rahilly, S. (Stephen), Wareham, N.J. (Nick), Speliotes, E.K. (Elizabeth), Fox, C.S. (Caroline), Laakso, M. (Markku), Loos, R.J.F. (Ruth), and Aulchenko, Y.S. (Yurii)
Abstract: Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10-6) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10-26) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10-11) and one near SPRY2 (P = 3 × 10-8). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
Published: 2011
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23. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

Author: Elks, C.E. (Cathy), Perry, J.R.B. (John), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (Chunyan), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (Enda), Cousminer, D.L. (Diana), Gudbjartsson, D.F. (Daniel), Esko, T. (Tõnu), Feenstra, B. (Bjarke), Hottenga, J.J. (Jouke Jan), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (Peng), Mangino, M. (Massimo), Marongiu, M. (Mara), McArdle, P.F. (Patrick), Smith, A.V. (Albert Vernon), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (Jing Hua), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Ulivi, S. (Shelia), Warrington, N.M. (Nicole), Zgaga, L. (Lina), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (Thor), Bandinelli, S. (Stefania), Barroso, I.E. (Inês), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Blackburn, H. (Hannah), Boerwinkle, E.A. (Eric), Buring, J.E. (Julie), Busonero, F., Campbell, H. (Harry), Chanock, S.J. (Stephen), Chen, W. (Wei), Cornelis, M. (Marilyn), Couper, D.J. (David), Coviello, A.D. (Andrea), Adamo, P. (Pio) d', Faire, U. (Ulf) de, Geus, E.J.C. (Eco) de, Deloukas, P. (Panagiotis), Döring, A. (Angela), Easton, D.F. (Douglas), Eiriksdottir, G. (Gudny), Emilsson, V. (Valur), Eriksson, J.G. (Johan), Ferrucci, L. (Luigi), Folsom, A.R. (Aaron), Foroud, T. (Tatiana), Garcia, M. (Melissa), Gasparini, P. (Paolo), Geller, F. (Frank), Gieger, C. (Christian), Gudnason, V. (Vilmundur), Hall, A.S. (Alistair), Hankinson, S.E. (Susan), Ferreli, L. (Liana), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (Frank), Illig, T. (Thomas), Järvelin, M.R., Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K-T. (Kay-Tee), Kiel, D.P. (Douglas), Kilpelänen, T.O. (Tuomas), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S.E. (Joop), Li, S. (Shengxu), Liu, J. (Jianjun), Levy, D. (Daniel), Martin, N.G. (Nicholas), Melbye, M. (Mads), Mooser, V. (Vincent), Murray, J.C. (Jeffrey), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (Mari), Ness, A.R. (Andrew), Northstone, K. (Kate), Oostra, B.A. (Ben), Peacock, M. (Munro), Palmer, C. (Cameron), Palotie, A. (Aarno), Paré, G. (Guillaume), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Peltonen, L. (Leena Johanna), Pennell, C.E. (Craig), Pharoah, P.D.P. (Paul), Polasek, O. (Ozren), Plump, A.S. (Andrew), Pouta, A. (Anneli), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D., Schork, N.J. (Nicholas), Scuteri, A. (Angelo), Segrè, A.V. (Ayellet), Shuldiner, A.R. (Alan), Soranzo, N. (Nicole), Sovio, U. (Ulla), Srinivasan, S.R. (Sathanur), Strachan, D.P. (David), Tammesoo, M.L., Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Tsui, K. (Kim), Tryggvadottir, L. (Laufey), Tyrer, J.P. (Jonathan), Uda, M. (Manuela), Dam, R.M. (Rob) van, Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Wichmann, H.E. (Heinz Erich), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (James), Wright, A.F. (Alan), Young, L. (Lauren), Zhai, G. (Guangju), Zhuang, W.V., Bierut, L.J. (Laura), Boomsma, D.I. (Dorret), Boyd, H.A. (Heather), Crisponi, L. (Laura), Demerath, E.W. (Ellen), Tikka-Kleemola, P. (Päivi), Econs, M.J. (Michael), Harris, T.B. (Tamara), Hunter, D. (David), Loos, R.J.F. (Ruth), Metspalu, A. (Andres), Montgomery, G.W. (Grant), Ridker, P.M. (Paul), Spector, T.D. (Timothy), Streeten, E.A. (Elizabeth), Stefansson, K. (Kari), Thorsteinsdottir, U. (Unnur), Uitterlinden, A.G. (André), Widen, E. (Elisabeth), Murabito, J. (Joanne), Ong, K. (Ken), Weedon, M.N. (Michael), Elks, C.E. (Cathy), Perry, J.R.B. (John), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (Chunyan), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (Enda), Cousminer, D.L. (Diana), Gudbjartsson, D.F. (Daniel), Esko, T. (Tõnu), Feenstra, B. (Bjarke), Hottenga, J.J. (Jouke Jan), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (Peng), Mangino, M. (Massimo), Marongiu, M. (Mara), McArdle, P.F. (Patrick), Smith, A.V. (Albert Vernon), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (Jing Hua), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Ulivi, S. (Shelia), Warrington, N.M. (Nicole), Zgaga, L. (Lina), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (Thor), Bandinelli, S. (Stefania), Barroso, I.E. (Inês), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Blackburn, H. (Hannah), Boerwinkle, E.A. (Eric), Buring, J.E. (Julie), Busonero, F., Campbell, H. (Harry), Chanock, S.J. (Stephen), Chen, W. (Wei), Cornelis, M. (Marilyn), Couper, D.J. (David), Coviello, A.D. (Andrea), Adamo, P. (Pio) d', Faire, U. (Ulf) de, Geus, E.J.C. (Eco) de, Deloukas, P. (Panagiotis), Döring, A. (Angela), Easton, D.F. (Douglas), Eiriksdottir, G. (Gudny), Emilsson, V. (Valur), Eriksson, J.G. (Johan), Ferrucci, L. (Luigi), Folsom, A.R. (Aaron), Foroud, T. (Tatiana), Garcia, M. (Melissa), Gasparini, P. (Paolo), Geller, F. (Frank), Gieger, C. (Christian), Gudnason, V. (Vilmundur), Hall, A.S. (Alistair), Hankinson, S.E. (Susan), Ferreli, L. (Liana), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (Frank), Illig, T. (Thomas), Järvelin, M.R., Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K-T. (Kay-Tee), Kiel, D.P. (Douglas), Kilpelänen, T.O. (Tuomas), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S.E. (Joop), Li, S. (Shengxu), Liu, J. (Jianjun), Levy, D. (Daniel), Martin, N.G. (Nicholas), Melbye, M. (Mads), Mooser, V. (Vincent), Murray, J.C. (Jeffrey), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (Mari), Ness, A.R. (Andrew), Northstone, K. (Kate), Oostra, B.A. (Ben), Peacock, M. (Munro), Palmer, C. (Cameron), Palotie, A. (Aarno), Paré, G. (Guillaume), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Peltonen, L. (Leena Johanna), Pennell, C.E. (Craig), Pharoah, P.D.P. (Paul), Polasek, O. (Ozren), Plump, A.S. (Andrew), Pouta, A. (Anneli), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Ring, S.M. (Susan), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D., Schork, N.J. (Nicholas), Scuteri, A. (Angelo), Segrè, A.V. (Ayellet), Shuldiner, A.R. (Alan), Soranzo, N. (Nicole), Sovio, U. (Ulla), Srinivasan, S.R. (Sathanur), Strachan, D.P. (David), Tammesoo, M.L., Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Tsui, K. (Kim), Tryggvadottir, L. (Laufey), Tyrer, J.P. (Jonathan), Uda, M. (Manuela), Dam, R.M. (Rob) van, Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Wichmann, H.E. (Heinz Erich), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (James), Wright, A.F. (Alan), Young, L. (Lauren), Zhai, G. (Guangju), Zhuang, W.V., Bierut, L.J. (Laura), Boomsma, D.I. (Dorret), Boyd, H.A. (Heather), Crisponi, L. (Laura), Demerath, E.W. (Ellen), Tikka-Kleemola, P. (Päivi), Econs, M.J. (Michael), Harris, T.B. (Tamara), Hunter, D. (David), Loos, R.J.F. (Ruth), Metspalu, A. (Andres), Montgomery, G.W. (Grant), Ridker, P.M. (Paul), Spector, T.D. (Timothy), Streeten, E.A. (Elizabeth), Stefansson, K. (Kari), Thorsteinsdottir, U. (Unnur), Uitterlinden, A.G. (André), Widen, E. (Elisabeth), Murabito, J. (Joanne), Ong, K. (Ken), and Weedon, M.N. (Michael)
Abstract: To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10 -60) and 9q31.2 (P = 2.2 × 10 -33), we identified 30 new menarche loci (all P < 5 × 10 -8) and found suggestive evidence for a further 10 loci (P < 1.9 × 10 -6). The new loci included four previously associated
Published: 2010
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24. An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility loci for osteoporosis-related traits

Author: Hsu, C.Y. (Chao), Zillikens, M.C. (Carola), Wilson, S.G. (Scott), Farber, C.R. (Charles), Demissie, S. (Serkalem), Soranzo, N. (Nicole), Bianchi, E.N. (Estelle), Grundberg, E. (Elin), Liang, L. (Liming), Richards, J.B. (Brent), Estrada Gil, K. (Karol), Zhou, Y. (Yanhua), Nas, A. (Atila) van, Moffatt, M.F. (Miriam), Zhai, G. (Guangju), Hofman, A. (Albert), Meurs, J.B.J. (Joyce) van, Pols, H.A.P. (Huib), Price, R.I. (Roger Ian), Nilsson, O. (Ola), Pastinen, T. (Tomi), Cupples, L.A. (Adrienne), Lusis, A.J. (Aldons Jake), Schadt, E.E. (Eric), Uitterlinden, A.G. (André), Kiel, D.P. (Douglas), Rivadeneira Ramirez, F. (Fernando), Spector, T.D. (Timothy), Karasik, D. (David), Ferrari, S.L. (Serge), Hsu, C.Y. (Chao), Zillikens, M.C. (Carola), Wilson, S.G. (Scott), Farber, C.R. (Charles), Demissie, S. (Serkalem), Soranzo, N. (Nicole), Bianchi, E.N. (Estelle), Grundberg, E. (Elin), Liang, L. (Liming), Richards, J.B. (Brent), Estrada Gil, K. (Karol), Zhou, Y. (Yanhua), Nas, A. (Atila) van, Moffatt, M.F. (Miriam), Zhai, G. (Guangju), Hofman, A. (Albert), Meurs, J.B.J. (Joyce) van, Pols, H.A.P. (Huib), Price, R.I. (Roger Ian), Nilsson, O. (Ola), Pastinen, T. (Tomi), Cupples, L.A. (Adrienne), Lusis, A.J. (Aldons Jake), Schadt, E.E. (Eric), Uitterlinden, A.G. (André), Kiel, D.P. (Douglas), Rivadeneira Ramirez, F. (Fernando), Spector, T.D. (Timothy), Karasik, D. (David), and Ferrari, S.L. (Serge)
Abstract: Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW). A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p=3.6*10-8), 2q11.2 (
Published: 2010
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25. Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis

Author: Meurs, J.B.J. (Joyce) van, Trikalinos, T.A. (Thomas), Ralston, S.H. (Stuart), Balcells, S. (Susana), Brandi, M.L., Brixen, K. (Kim), Kiel, D.P. (Douglas), Langdahl, B.L. (Bente), Lips, P. (Paul), Ljunggren, O. (Östen), Lorenc, R. (Roman), Obermayer-Pietsch, B. (Barbara), Ohlsson, C. (Claes), Pettersson, U. (Ulrika), Reid, D.M. (David), Rousseau, M.F. (Francois), Scollen, S. (Serena), Van Hul, W. (Wim), Agueda, L. (Lidia), Åkesson, K. (Kristina), Benevolenskaya, L.I. (Lidia), Ferrari, S.L. (Serge), Hallmans, G. (Göran), Hofman, A. (Albert), Husted, L.B. (Lise Bjerre), Kruk, M. (Marcin), Kaptoge, S. (Stephen), Karasik, D. (David), Karlsson, M. (Magnus), Lorentzon, M. (Mattias), Masi, L. (Laura), McGuigan, F.E., Mellström, D. (Dan), Mosekilde, L. (Leif), Nogues, X. (Xavier), Pols, H.A.P. (Huib), Reeve, J. (Jonathan), Renner, W. (Wilfried), Rivadeneira Ramirez, F. (Fernando), Schoor, N.M. (Natasja) van, Weber, K. (Kurt), Ioannidis, J.P.A. (John), Uitterlinden, A.G. (André), Meurs, J.B.J. (Joyce) van, Trikalinos, T.A. (Thomas), Ralston, S.H. (Stuart), Balcells, S. (Susana), Brandi, M.L., Brixen, K. (Kim), Kiel, D.P. (Douglas), Langdahl, B.L. (Bente), Lips, P. (Paul), Ljunggren, O. (Östen), Lorenc, R. (Roman), Obermayer-Pietsch, B. (Barbara), Ohlsson, C. (Claes), Pettersson, U. (Ulrika), Reid, D.M. (David), Rousseau, M.F. (Francois), Scollen, S. (Serena), Van Hul, W. (Wim), Agueda, L. (Lidia), Åkesson, K. (Kristina), Benevolenskaya, L.I. (Lidia), Ferrari, S.L. (Serge), Hallmans, G. (Göran), Hofman, A. (Albert), Husted, L.B. (Lise Bjerre), Kruk, M. (Marcin), Kaptoge, S. (Stephen), Karasik, D. (David), Karlsson, M. (Magnus), Lorentzon, M. (Mattias), Masi, L. (Laura), McGuigan, F.E., Mellström, D. (Dan), Mosekilde, L. (Leif), Nogues, X. (Xavier), Pols, H.A.P. (Huib), Reeve, J. (Jonathan), Renner, W. (Wilfried), Rivadeneira Ramirez, F. (Fernando), Schoor, N.M. (Natasja) van, Weber, K. (Kurt), Ioannidis, J.P.A. (John), and Uitterlinden, A.G. (André)
Abstract: Context: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population. Objective: To generate large-scale evidence on whether 2 common variants of LRP5 (Val667Met, Ala1330Val) and 1 variant of LRP6 (Ile1062Val) are associated with BMD and fracture risk. Design and Setting: Prospective, multicenter, collaborative study of individuallevel data on 37 534 individuals from 18 participating teams in Europe and North America. Data were collected between September 2004 and January 2007; analysis of the collected data was performed between February and May 2007. Bone mineral density was assessed by dual-energy x-ray absorptiometry. Fractures were identified via questionnaire, medical records, or radiographic documentation; incident fracture data were available for some cohorts, ascertained via routine surveillance methods, including radiographic examination for vertebral fractures. Main Outcome Measures: Bone mineral density of the lumbar spine and femoral neck; prevalence of all fractures and vertebral fractures. Results: The Met667 allele of LRP5 was associated with reduced lumbar spine BMD (n=25 052 [number of participants with available data]; 20-mg/cm2lower BMD per Met667 allele copy; P=3.3 × 10-8), as was the Val1330 allele (n=24 812; 14-mg/cm2lower BMD per Val1330 copy; P=2.6 × 10-9). Similar effects were observed for femoral neck BMD, with a decrease of 11 mg/cm2(P=3.8 × 10-5) and 8 mg/cm2(P=5.0 × 10-6) for the Met667 and Val1330 alleles, respectively (n=25 193). Findings were consistent across studies for both LRP5 alleles. Both alleles were associated with vertebral fractures (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.08-1.47 for Met667 [2001 fractures among 20 488 individuals] and OR, 1.12; 95% CI, 1.01-1.24 for Val1330 [1988 fractures among 20 096 individuals]). Risk of all fract
Published: 2008
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25 results on '"Karasik, D. (David)"'

1. Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women

2. Genetic basis of falling risk susceptibility in the UK Biobank Study

3. Genetics of Bone and Muscle Interactions in Humans

4. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

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

6. Correction: The complex genetics of gait speed: Genome-wide metaanalysis approach [Aging, (Albany NY), 9, 1, (2017), (209-246)]doi 10.18632/aging.101151

7. Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis

8. Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus

9. Gene transcripts associated with muscle strength: A CHARGE meta-analysis of 7,781 persons

10. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture

11. Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci

12. Rare coding variants and X-linked loci associated with age at menarche

13. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche

14. Genetic diversity is a predictor of mortality in humans

15. A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus

16. Association of heat shock proteins with all-cause mortality

17. A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple loci implicated in s

18. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

19. A genome-wide association study of aging

20. Large common deletions associate with mortality at old age

21. Genetic determinants of serum testosterone concentrations in men

22. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile

23. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

24. An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility loci for osteoporosis-related traits

25. Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis

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