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1. Pleiotropy among common genetic loci identified for cardiometabolic disorders and C-reactive protein

Author

Ligthart, S. (Symen), Vries, P.S. (Paul) de, Uitterlinden, A.G. (André), Hofman, A. (Albert), Franco, O.H. (Oscar), Chasman, D.I. (Daniel), Dehghan, A. (Abbas), Dupuis, J. (Josée), Barbalic, M. (maja), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Lu, C. (Chen), Pellikka, N. (Niina), Wallaschofski, H. (Henri), Kettunen, J. (Johannes), Henneman, P. (Peter), Baumert, J. (Jens), Strachan, D.P. (David), Fuchsberger, C. (Christian), Vitart, V. (Veronique), Wilson, J.F. (James F), Paré, G. (Guillaume), Naitza, S. (Silvia), Rudock, M.E. (Megan), Surakka, I. (Ida), Geus, E.J.C. (Eco) de, Alizadeh, B.Z. (Behrooz), Guralnik, J.M. (Jack), Shuldiner, A.R. (Alan), Tanaka, T. (Toshiko), Zee, R.Y.L. (Robert), Schnabel, R.B. (Renate), Nambi, V. (Vijay), Kavousi, M. (Maryam), Ripatti, S. (Samuli), Nauck, M. (Matthias), Smith, N.L. (Nicholas L.), Smith, A.V. (Albert Vernon), Sundvall, J. (Jouko), Scheet, P. (Paul), Liu, Y. (YongMei), Ruokonen, A. (Aimo), Rose, L.M. (Lynda), Larson, M.G. (Martin), Hoogeveen, R.C. (Ron), Freimer, N.B. (Nelson), Teumer, A. (Alexander), Tracy, R.P. (Russell), Launer, L.J. (Lenore), Buring, J.E. (Julie), Yamamoto, J.F. (Jennifer), Folsom, A.R. (Aaron), Sijbrands, E.J.G. (Eric), Pankow, J.S. (James), Elliott, P. (Paul), Keaney, J.F. (John), Sun, W. (Wei), Sarin, A.-P., Fontes, M. (Michel), Badola, S. (Sunita), Astor, B.C. (Brad), Pouta, A. (Anneli), Werda, K. (Karl), Greiser, K.H. (Karin Halina), Kuss, O. (Oliver), Schwabedissen, H.E.M.Z. (Henriette E. Meyer Zu), Thiery, J. (Joachim), Jamshidi, Y. (Yalda), Nolte, I.M. (Ilja M.), Soranzo, N. (Nicole), Spector, T.D. (Timothy), Völzke, H. (Henry), Parker, A.N. (Alex), Aspelund, T. (Thor), Bates, D. (David), Young, L. (Lauren), Tsui, K. (Kim), Siscovick, D.S. (David), Guo, X. (Xiuqing), Rotter, J.I. (Jerome I.), Uda, M. (Manuela), Schlessinger, D., Rudan, I. (Igor), Hicks, A.A. (Andrew), Penninx, B.W.J.H. (Brenda), Thorand, B. (Barbara), Gieger, C. (Christian), Coresh, J. (Josef), Willemsen, G.A.H.M. (Gonneke), Harris, T.B. (Tamara), Jarvelin, M.-R. (Marjo-Riitta), Rice, K.M. (Kenneth), Radke, D. (Dörte), Salomaa, V. (Veikko), Willems van Dijk, J.A.P. (Ko), Boerwinkle, E.A. (Eric), Vasan, R.S. (Ramachandran Srini), Ferrucci, L. (Luigi), Gibson, Q. (Quince), Bandinelli, S. (Stefania), Snieder, H. (Harold), Boomsma, D.I. (Dorret), Xiao, X. (Xiangjun), Campbell, H. (Harry), Hayward, C. (Caroline), Pramstaller, P.P. (Peter Paul), Duijn, C.M. (Cornelia) van, Peltonen, L. (Leena Johanna), Psaty, B.M. (Bruce), Gudnason, V. (Vilmundur), Ridker, P.M. (Paul), Homuth, G. (Georg), Koenig, W. (Wolfgang), Ballantyne, C. (Christie), Witteman, J.C.M. (Jacqueline), Benjamin, E.J. (Emelia), Perola, M. (Markus), Chasman., D.I. (Daniel I.), Ligthart, S. (Symen), Vries, P.S. (Paul) de, Uitterlinden, A.G. (André), Hofman, A. (Albert), Franco, O.H. (Oscar), Chasman, D.I. (Daniel), Dehghan, A. (Abbas), Dupuis, J. (Josée), Barbalic, M. (maja), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Lu, C. (Chen), Pellikka, N. (Niina), Wallaschofski, H. (Henri), Kettunen, J. (Johannes), Henneman, P. (Peter), Baumert, J. (Jens), Strachan, D.P. (David), Fuchsberger, C. (Christian), Vitart, V. (Veronique), Wilson, J.F. (James F), Paré, G. (Guillaume), Naitza, S. (Silvia), Rudock, M.E. (Megan), Surakka, I. (Ida), Geus, E.J.C. (Eco) de, Alizadeh, B.Z. (Behrooz), Guralnik, J.M. (Jack), Shuldiner, A.R. (Alan), Tanaka, T. (Toshiko), Zee, R.Y.L. (Robert), Schnabel, R.B. (Renate), Nambi, V. (Vijay), Kavousi, M. (Maryam), Ripatti, S. (Samuli), Nauck, M. (Matthias), Smith, N.L. (Nicholas L.), Smith, A.V. (Albert Vernon), Sundvall, J. (Jouko), Scheet, P. (Paul), Liu, Y. (YongMei), Ruokonen, A. (Aimo), Rose, L.M. (Lynda), Larson, M.G. (Martin), Hoogeveen, R.C. (Ron), Freimer, N.B. (Nelson), Teumer, A. (Alexander), Tracy, R.P. (Russell), Launer, L.J. (Lenore), Buring, J.E. (Julie), Yamamoto, J.F. (Jennifer), Folsom, A.R. (Aaron), Sijbrands, E.J.G. (Eric), Pankow, J.S. (James), Elliott, P. (Paul), Keaney, J.F. (John), Sun, W. (Wei), Sarin, A.-P., Fontes, M. (Michel), Badola, S. (Sunita), Astor, B.C. (Brad), Pouta, A. (Anneli), Werda, K. (Karl), Greiser, K.H. (Karin Halina), Kuss, O. (Oliver), Schwabedissen, H.E.M.Z. (Henriette E. Meyer Zu), Thiery, J. (Joachim), Jamshidi, Y. (Yalda), Nolte, I.M. (Ilja M.), Soranzo, N. (Nicole), Spector, T.D. (Timothy), Völzke, H. (Henry), Parker, A.N. (Alex), Aspelund, T. (Thor), Bates, D. (David), Young, L. (Lauren), Tsui, K. (Kim), Siscovick, D.S. (David), Guo, X. (Xiuqing), Rotter, J.I. (Jerome I.), Uda, M. (Manuela), Schlessinger, D., Rudan, I. (Igor), Hicks, A.A. (Andrew), Penninx, B.W.J.H. (Brenda), Thorand, B. (Barbara), Gieger, C. (Christian), Coresh, J. (Josef), Willemsen, G.A.H.M. (Gonneke), Harris, T.B. (Tamara), Jarvelin, M.-R. (Marjo-Riitta), Rice, K.M. (Kenneth), Radke, D. (Dörte), Salomaa, V. (Veikko), Willems van Dijk, J.A.P. (Ko), Boerwinkle, E.A. (Eric), Vasan, R.S. (Ramachandran Srini), Ferrucci, L. (Luigi), Gibson, Q. (Quince), Bandinelli, S. (Stefania), Snieder, H. (Harold), Boomsma, D.I. (Dorret), Xiao, X. (Xiangjun), Campbell, H. (Harry), Hayward, C. (Caroline), Pramstaller, P.P. (Peter Paul), Duijn, C.M. (Cornelia) van, Peltonen, L. (Leena Johanna), Psaty, B.M. (Bruce), Gudnason, V. (Vilmundur), Ridker, P.M. (Paul), Homuth, G. (Georg), Koenig, W. (Wolfgang), Ballantyne, C. (Christie), Witteman, J.C.M. (Jacqueline), Benjamin, E.J. (Emelia), Perola, M. (Markus), and Chasman., D.I. (Daniel I.)

Abstract

Pleiotropic genetic variants have independent effects on different phenotypes. C-reactive protein (CRP) is associated with several cardiometabolic phenotypes. Shared genetic backgrounds may partially underlie these associations. We conducted a genome-wide analysis to identify the shared genetic background of inflammation and cardiometabolic phenotypes using published genome-wide association studies (GWAS). We also evaluated whether the pleiotropic effects of such loci were biological or mediated in nature. First, we examined whether 283 common variants identified for 10 cardiometabolic phenotypes in GWAS are associated with CRP level. Second, we tested whether 18 variants identified for serum CRP are associated with 10 cardiometabolic phenotypes. We used a Bonferroni corrected p-value of 1.1×10-04 (0.05/463) as a threshold of significance. We evaluated the independent pleiotropic effect on both phenotypes using individual level data from the Women Genome Health Study. Evaluating the genetic overlap between inflammation and cardiometabolic phenotypes, we found 13 pleiotropic regions. Additional analyses showed that 6 regions (APOC1, HNF1A, IL6R, PPP1R3B, HNF4A and IL1F10) appeared to have a pleiotropic effect on CRP independent of the effects on the cardiometabolic phenotypes. These included loci where individuals carrying the risk allele for CRP encounter higher lipid levels and risk of type 2 diabetes. In addition, 5 regions (GCKR, PABPC4, BCL7B, FTO and TMEM18) had an effect on CRP largely mediated through the cardiometabolic phenotypes. In conclusion, our results show genetic pleiotropy among inflammation and cardiometabolic phenotypes. In addition to reverse causation, our data suggests that pleiotropic genetic variants partially underlie the association between CRP and cardiometabolic phenotypes.

Published
2015
Full Text
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2. Pleiotropy among common genetic loci identified for cardiometabolic disorders and C-reactive protein

Author

Ligthart, S. (Symen), Vries, P.S. (Paul) de, Uitterlinden, A.G. (André), Hofman, A. (Albert), Franco, O.H. (Oscar), Chasman, D.I. (Daniel), Dehghan, A. (Abbas), Dupuis, J. (Josée), Barbalic, M. (maja), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Lu, C. (Chen), Pellikka, N. (Niina), Wallaschofski, H. (Henri), Kettunen, J. (Johannes), Henneman, P. (Peter), Baumert, J. (Jens), Strachan, D.P. (David), Fuchsberger, C. (Christian), Vitart, V. (Veronique), Wilson, J.F. (James F), Paré, G. (Guillaume), Naitza, S. (Silvia), Rudock, M.E. (Megan), Surakka, I. (Ida), Geus, E.J.C. (Eco) de, Alizadeh, B.Z. (Behrooz), Guralnik, J.M. (Jack), Shuldiner, A.R. (Alan), Tanaka, T. (Toshiko), Zee, R.Y.L. (Robert), Schnabel, R.B. (Renate), Nambi, V. (Vijay), Kavousi, M. (Maryam), Ripatti, S. (Samuli), Nauck, M. (Matthias), Smith, N.L. (Nicholas L.), Smith, A.V. (Albert Vernon), Sundvall, J. (Jouko), Scheet, P. (Paul), Liu, Y. (YongMei), Ruokonen, A. (Aimo), Rose, L.M. (Lynda), Larson, M.G. (Martin), Hoogeveen, R.C. (Ron), Freimer, N.B. (Nelson), Teumer, A. (Alexander), Tracy, R.P. (Russell), Launer, L.J. (Lenore), Buring, J.E. (Julie), Yamamoto, J.F. (Jennifer), Folsom, A.R. (Aaron), Sijbrands, E.J.G. (Eric), Pankow, J.S. (James), Elliott, P. (Paul), Keaney, J.F. (John), Sun, W. (Wei), Sarin, A.-P., Fontes, M. (Michel), Badola, S. (Sunita), Astor, B.C. (Brad), Pouta, A. (Anneli), Werda, K. (Karl), Greiser, K.H. (Karin Halina), Kuss, O. (Oliver), Schwabedissen, H.E.M.Z. (Henriette E. Meyer Zu), Thiery, J. (Joachim), Jamshidi, Y. (Yalda), Nolte, I.M. (Ilja M.), Soranzo, N. (Nicole), Spector, T.D. (Timothy), Völzke, H. (Henry), Parker, A.N. (Alex), Aspelund, T. (Thor), Bates, D. (David), Young, L. (Lauren), Tsui, K. (Kim), Siscovick, D.S. (David), Guo, X. (Xiuqing), Rotter, J.I. (Jerome I.), Uda, M. (Manuela), Schlessinger, D., Rudan, I. (Igor), Hicks, A.A. (Andrew), Penninx, B.W.J.H. (Brenda), Thorand, B. (Barbara), Gieger, C. (Christian), Coresh, J. (Josef), Willemsen, G.A.H.M. (Gonneke), Harris, T.B. (Tamara), Jarvelin, M.-R. (Marjo-Riitta), Rice, K.M. (Kenneth), Radke, D. (Dörte), Salomaa, V. (Veikko), Willems van Dijk, J.A.P. (Ko), Boerwinkle, E.A. (Eric), Vasan, R.S. (Ramachandran Srini), Ferrucci, L. (Luigi), Gibson, Q. (Quince), Bandinelli, S. (Stefania), Snieder, H. (Harold), Boomsma, D.I. (Dorret), Xiao, X. (Xiangjun), Campbell, H. (Harry), Hayward, C. (Caroline), Pramstaller, P.P. (Peter Paul), Duijn, C.M. (Cornelia) van, Peltonen, L. (Leena Johanna), Psaty, B.M. (Bruce), Gudnason, V. (Vilmundur), Ridker, P.M. (Paul), Homuth, G. (Georg), Koenig, W. (Wolfgang), Ballantyne, C. (Christie), Witteman, J.C.M. (Jacqueline), Benjamin, E.J. (Emelia), Perola, M. (Markus), Chasman., D.I. (Daniel I.), Ligthart, S. (Symen), Vries, P.S. (Paul) de, Uitterlinden, A.G. (André), Hofman, A. (Albert), Franco, O.H. (Oscar), Chasman, D.I. (Daniel), Dehghan, A. (Abbas), Dupuis, J. (Josée), Barbalic, M. (maja), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Lu, C. (Chen), Pellikka, N. (Niina), Wallaschofski, H. (Henri), Kettunen, J. (Johannes), Henneman, P. (Peter), Baumert, J. (Jens), Strachan, D.P. (David), Fuchsberger, C. (Christian), Vitart, V. (Veronique), Wilson, J.F. (James F), Paré, G. (Guillaume), Naitza, S. (Silvia), Rudock, M.E. (Megan), Surakka, I. (Ida), Geus, E.J.C. (Eco) de, Alizadeh, B.Z. (Behrooz), Guralnik, J.M. (Jack), Shuldiner, A.R. (Alan), Tanaka, T. (Toshiko), Zee, R.Y.L. (Robert), Schnabel, R.B. (Renate), Nambi, V. (Vijay), Kavousi, M. (Maryam), Ripatti, S. (Samuli), Nauck, M. (Matthias), Smith, N.L. (Nicholas L.), Smith, A.V. (Albert Vernon), Sundvall, J. (Jouko), Scheet, P. (Paul), Liu, Y. (YongMei), Ruokonen, A. (Aimo), Rose, L.M. (Lynda), Larson, M.G. (Martin), Hoogeveen, R.C. (Ron), Freimer, N.B. (Nelson), Teumer, A. (Alexander), Tracy, R.P. (Russell), Launer, L.J. (Lenore), Buring, J.E. (Julie), Yamamoto, J.F. (Jennifer), Folsom, A.R. (Aaron), Sijbrands, E.J.G. (Eric), Pankow, J.S. (James), Elliott, P. (Paul), Keaney, J.F. (John), Sun, W. (Wei), Sarin, A.-P., Fontes, M. (Michel), Badola, S. (Sunita), Astor, B.C. (Brad), Pouta, A. (Anneli), Werda, K. (Karl), Greiser, K.H. (Karin Halina), Kuss, O. (Oliver), Schwabedissen, H.E.M.Z. (Henriette E. Meyer Zu), Thiery, J. (Joachim), Jamshidi, Y. (Yalda), Nolte, I.M. (Ilja M.), Soranzo, N. (Nicole), Spector, T.D. (Timothy), Völzke, H. (Henry), Parker, A.N. (Alex), Aspelund, T. (Thor), Bates, D. (David), Young, L. (Lauren), Tsui, K. (Kim), Siscovick, D.S. (David), Guo, X. (Xiuqing), Rotter, J.I. (Jerome I.), Uda, M. (Manuela), Schlessinger, D., Rudan, I. (Igor), Hicks, A.A. (Andrew), Penninx, B.W.J.H. (Brenda), Thorand, B. (Barbara), Gieger, C. (Christian), Coresh, J. (Josef), Willemsen, G.A.H.M. (Gonneke), Harris, T.B. (Tamara), Jarvelin, M.-R. (Marjo-Riitta), Rice, K.M. (Kenneth), Radke, D. (Dörte), Salomaa, V. (Veikko), Willems van Dijk, J.A.P. (Ko), Boerwinkle, E.A. (Eric), Vasan, R.S. (Ramachandran Srini), Ferrucci, L. (Luigi), Gibson, Q. (Quince), Bandinelli, S. (Stefania), Snieder, H. (Harold), Boomsma, D.I. (Dorret), Xiao, X. (Xiangjun), Campbell, H. (Harry), Hayward, C. (Caroline), Pramstaller, P.P. (Peter Paul), Duijn, C.M. (Cornelia) van, Peltonen, L. (Leena Johanna), Psaty, B.M. (Bruce), Gudnason, V. (Vilmundur), Ridker, P.M. (Paul), Homuth, G. (Georg), Koenig, W. (Wolfgang), Ballantyne, C. (Christie), Witteman, J.C.M. (Jacqueline), Benjamin, E.J. (Emelia), Perola, M. (Markus), and Chasman., D.I. (Daniel I.)

Abstract

Pleiotropic genetic variants have independent effects on different phenotypes. C-reactive protein (CRP) is associated with several cardiometabolic phenotypes. Shared genetic backgrounds may partially underlie these associations. We conducted a genome-wide analysis to identify the shared genetic background of inflammation and cardiometabolic phenotypes using published genome-wide association studies (GWAS). We also evaluated whether the pleiotropic effects of such loci were biological or mediated in nature. First, we examined whether 283 common variants identified for 10 cardiometabolic phenotypes in GWAS are associated with CRP level. Second, we tested whether 18 variants identified for serum CRP are associated with 10 cardiometabolic phenotypes. We used a Bonferroni corrected p-value of 1.1×10-04 (0.05/463) as a threshold of significance. We evaluated the independent pleiotropic effect on both phenotypes using individual level data from the Women Genome Health Study. Evaluating the genetic overlap between inflammation and cardiometabolic phenotypes, we found 13 pleiotropic regions. Additional analyses showed that 6 regions (APOC1, HNF1A, IL6R, PPP1R3B, HNF4A and IL1F10) appeared to have a pleiotropic effect on CRP independent of the effects on the cardiometabolic phenotypes. These included loci where individuals carrying the risk allele for CRP encounter higher lipid levels and risk of type 2 diabetes. In addition, 5 regions (GCKR, PABPC4, BCL7B, FTO and TMEM18) had an effect on CRP largely mediated through the cardiometabolic phenotypes. In conclusion, our results show genetic pleiotropy among inflammation and cardiometabolic phenotypes. In addition to reverse causation, our data suggests that pleiotropic genetic variants partially underlie the association between CRP and cardiometabolic phenotypes.

Published
2015
Full Text
View/download PDF

3. Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

Author

Medici, M. (Marco), Porcu, E. (Eleonora), Pistis, G. (Giorgio), Teumer, A. (Alexander), Brown, S.J. (Stephen), Jensen, R.A. (Richard), Rawal, R. (Rajesh), Roef, G.L. (Greet), Plantinga, T.S. (Theo S.), Vermeulen, S.H.H.M. (Sita), Lahti, J. (Jari), Simmonds, M.C. (Mark), Husemoen, L.L.N. (Lise Lotte), Freathy, R.M. (Rachel), Shields, B.M. (Beverley), Pietzner, D. (Diana), Nagy, R. (Rebecca), Broer, L. (Linda), Chaker, L. (Layal), Korevaar, T.I.M. (Tim), Plia, M.G. (Maria Grazia), Sala, C. (Cinzia), Völker, U. (Uwe), Richards, J.B. (Brent), Sweep, F.C. (Fred), Gieger, C. (Christian), Corre, T. (Tanguy), Kajantie, E. (Eero), Thuesen, L. (Leif), Taes, Y.E. (Youri), Visser, W.E. (Edward), Hattersley, A.T. (Andrew), Kratzsch, J. (Jürgen), Hamilton, A. (Amy), Li, W. (Wei), Homuth, G. (Georg), Lobina, M. (Monia), Mariotti, S. (Stefano), Soranzo, N. (Nicole), Cocca, M. (Massimiliano), Nauck, M. (Matthias), Spielhagen, C. (Christin), Ross, H.A. (Alec), Arnold, A.M. (Alice), Bunt, M. (Martijn) van de, Liyanarachchi, S. (Sandya), Heier, M. (Margit), Grabe, H.J. (Hans Jörgen), Masciullo, C. (Corrado), Galesloot, T.E. (Tessel), Lim, E.M. (Ee Mun), Reischl, G. (Gunilla), Leedman, P.J. (Peter), Lai, S. (Sandra), Delitala, A. (Alessandro), Bremner, A. (Alexandra), Philips, D.I.W. (David I.), Beilby, J.P. (John), Mulas, A. (Antonella), Vocale, M. (Matteo), Abecasis, G.R. (Gonçalo), Forsen, T. (Tom), James, A. (Alan), Widen, E. (Elisabeth), Hui, J. (Jennie), Prokisch, H. (Holger), Rietzschel, E.E. (Ernst), Palotie, A. (Aarno), Feddema, W. (Wouter), Fletcher, S.J. (Stephen), Schramm, K. (Katharina), Rotter, J.I. (Jerome), Kluttig, A. (Alexander), Radke, D. (Dörte), Traglia, M. (Michela), Surdulescu, G. (Gabriela), He, H. (Hao), Franklyn, J.A. (Jayne), Tiller, D. (Daniel), Vaidya, B. (Bijay), Meyer, T. (Thorsten), Jorgensen, T. (Torben), Hagen, K. (Knut), O'Leary, P.C. (Peter), Wichmann, E. (Eric), Hermus, A.R.M.M. (Ad), Psaty, B.M. (Bruce), Ittermann, T. (Till), Hofman, A. (Albert), Bosi, E. (Emanuele), Schlessinger, D. (David), Wallaschofski, H. (Henri), Pirastu, N. (Nicola), Aulchenko, Y.S. (Yurii), de la Chapelle, A. (Albert), Netea-Maier, R.T. (Romana), Gough, J.E. (Julie), Meyer zu Schwabedissen, H. (Henriette), Frayling, T.M. (Timothy), Kaufman, J.-M. (Jean-Marc), Linneberg, A. (Allan), Räikkönen, K. (Katri), Smit, J.W.A. (Jan), Kiemeney, L.A.L.M. (Bart), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Walsh, J.P. (John), Meisinger, C. (Christa), Heijer, M. (Martin) den, Visser, T.J. (Theo), Spector, T.D. (Timothy), Wilson, S.G. (Scott), Völzke, H. (Henry), Cappola, A.R. (Anne), Toniolo, D. (Daniela), Sanna, S. (Serena), Naitza, S. (Silvia), Peeters, R.P. (Robin), Medici, M. (Marco), Porcu, E. (Eleonora), Pistis, G. (Giorgio), Teumer, A. (Alexander), Brown, S.J. (Stephen), Jensen, R.A. (Richard), Rawal, R. (Rajesh), Roef, G.L. (Greet), Plantinga, T.S. (Theo S.), Vermeulen, S.H.H.M. (Sita), Lahti, J. (Jari), Simmonds, M.C. (Mark), Husemoen, L.L.N. (Lise Lotte), Freathy, R.M. (Rachel), Shields, B.M. (Beverley), Pietzner, D. (Diana), Nagy, R. (Rebecca), Broer, L. (Linda), Chaker, L. (Layal), Korevaar, T.I.M. (Tim), Plia, M.G. (Maria Grazia), Sala, C. (Cinzia), Völker, U. (Uwe), Richards, J.B. (Brent), Sweep, F.C. (Fred), Gieger, C. (Christian), Corre, T. (Tanguy), Kajantie, E. (Eero), Thuesen, L. (Leif), Taes, Y.E. (Youri), Visser, W.E. (Edward), Hattersley, A.T. (Andrew), Kratzsch, J. (Jürgen), Hamilton, A. (Amy), Li, W. (Wei), Homuth, G. (Georg), Lobina, M. (Monia), Mariotti, S. (Stefano), Soranzo, N. (Nicole), Cocca, M. (Massimiliano), Nauck, M. (Matthias), Spielhagen, C. (Christin), Ross, H.A. (Alec), Arnold, A.M. (Alice), Bunt, M. (Martijn) van de, Liyanarachchi, S. (Sandya), Heier, M. (Margit), Grabe, H.J. (Hans Jörgen), Masciullo, C. (Corrado), Galesloot, T.E. (Tessel), Lim, E.M. (Ee Mun), Reischl, G. (Gunilla), Leedman, P.J. (Peter), Lai, S. (Sandra), Delitala, A. (Alessandro), Bremner, A. (Alexandra), Philips, D.I.W. (David I.), Beilby, J.P. (John), Mulas, A. (Antonella), Vocale, M. (Matteo), Abecasis, G.R. (Gonçalo), Forsen, T. (Tom), James, A. (Alan), Widen, E. (Elisabeth), Hui, J. (Jennie), Prokisch, H. (Holger), Rietzschel, E.E. (Ernst), Palotie, A. (Aarno), Feddema, W. (Wouter), Fletcher, S.J. (Stephen), Schramm, K. (Katharina), Rotter, J.I. (Jerome), Kluttig, A. (Alexander), Radke, D. (Dörte), Traglia, M. (Michela), Surdulescu, G. (Gabriela), He, H. (Hao), Franklyn, J.A. (Jayne), Tiller, D. (Daniel), Vaidya, B. (Bijay), Meyer, T. (Thorsten), Jorgensen, T. (Torben), Hagen, K. (Knut), O'Leary, P.C. (Peter), Wichmann, E. (Eric), Hermus, A.R.M.M. (Ad), Psaty, B.M. (Bruce), Ittermann, T. (Till), Hofman, A. (Albert), Bosi, E. (Emanuele), Schlessinger, D. (David), Wallaschofski, H. (Henri), Pirastu, N. (Nicola), Aulchenko, Y.S. (Yurii), de la Chapelle, A. (Albert), Netea-Maier, R.T. (Romana), Gough, J.E. (Julie), Meyer zu Schwabedissen, H. (Henriette), Frayling, T.M. (Timothy), Kaufman, J.-M. (Jean-Marc), Linneberg, A. (Allan), Räikkönen, K. (Katri), Smit, J.W.A. (Jan), Kiemeney, L.A.L.M. (Bart), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Walsh, J.P. (John), Meisinger, C. (Christa), Heijer, M. (Martin) den, Visser, T.J. (Theo), Spector, T.D. (Timothy), Wilson, S.G. (Scott), Völzke, H. (Henry), Cappola, A.R. (Anne), Toniolo, D. (Daniela), Sanna, S. (Serena), Naitza, S. (Silvia), and Peeters, R.P. (Robin)

Abstract

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10-8) were detected at T

Published
2014
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4. Systematic identification of trans eQTLs as putative drivers of known disease associations

Author

Westra, H.J. (Harm-Jan), Peters, M.J. (Marjolein), Esko, T. (Tõnu), Yaghootkar, H. (Hanieh), Schurmann, C. (Claudia), Kettunen, J. (Johannes), Christiansen, M.W. (Mark), Fairfax, B.P. (Benjamin), Schramm, K. (Katharina), Powell, J.E. (Joseph), Zhernakova, A. (Alexandra), Veldink, J.H. (Jan), Berg, L.H. (Leonard) van den, Karjalainen, J. (Juha), Withoff, S. (Sebo), Uitterlinden, A.G. (André), Hofman, B., Rivadeneira Ramirez, F. (Fernando), Hoen, P.A.C. (Peter) 't, Reinmaa, E. (Eva), Fischer, K. (Kathelijn), Nelis, M. (Mari), Milani, A.L. (Alfredo), Melzer, D. (David), Ferrucci, L. (Luigi), Singleton, A.B. (Andrew), Hernandez, D.G. (Dena), Nalls, M.A. (Michael), Homuth, G. (Georg), Nauck, M.A. (Matthias), Radke, D. (Dörte), Vol̈ker, U. (Uwe), Perola, M. (Markus), Salomaa, V. (Veikko), Brody, J.A. (Jennifer A.), Suchy-Dicey, A. (Astrid), Gharib, S.A. (Sina), Enquobahrie, D., Lumley, T. (Thomas), Montgomery, G.W., Makino, S. (Seiko), Prokisch, H. (Holger), Herder, C. (Christian), Roden, M. (Michael), Grallert, H. (Harald), Meitinger, T. (Thomas), Strauch, K. (Konstantin), Li, Y. (Yunmin), Jansen, J.R.C. (Jos), Visscher, P.M. (Peter M.), Knight, J.C. (Julian), Psaty, B.M. (Bruce), Ripatti, S. (Samuli), Teumer, A. (Alexander), Frayling, T.M. (Timothy), Metspalu, A. (Andres), Meurs, J.B.J. (Joyce) van, Franke, L. (Lude), Westra, H.J. (Harm-Jan), Peters, M.J. (Marjolein), Esko, T. (Tõnu), Yaghootkar, H. (Hanieh), Schurmann, C. (Claudia), Kettunen, J. (Johannes), Christiansen, M.W. (Mark), Fairfax, B.P. (Benjamin), Schramm, K. (Katharina), Powell, J.E. (Joseph), Zhernakova, A. (Alexandra), Veldink, J.H. (Jan), Berg, L.H. (Leonard) van den, Karjalainen, J. (Juha), Withoff, S. (Sebo), Uitterlinden, A.G. (André), Hofman, B., Rivadeneira Ramirez, F. (Fernando), Hoen, P.A.C. (Peter) 't, Reinmaa, E. (Eva), Fischer, K. (Kathelijn), Nelis, M. (Mari), Milani, A.L. (Alfredo), Melzer, D. (David), Ferrucci, L. (Luigi), Singleton, A.B. (Andrew), Hernandez, D.G. (Dena), Nalls, M.A. (Michael), Homuth, G. (Georg), Nauck, M.A. (Matthias), Radke, D. (Dörte), Vol̈ker, U. (Uwe), Perola, M. (Markus), Salomaa, V. (Veikko), Brody, J.A. (Jennifer A.), Suchy-Dicey, A. (Astrid), Gharib, S.A. (Sina), Enquobahrie, D., Lumley, T. (Thomas), Montgomery, G.W., Makino, S. (Seiko), Prokisch, H. (Holger), Herder, C. (Christian), Roden, M. (Michael), Grallert, H. (Harald), Meitinger, T. (Thomas), Strauch, K. (Konstantin), Li, Y. (Yunmin), Jansen, J.R.C. (Jos), Visscher, P.M. (Peter M.), Knight, J.C. (Julian), Psaty, B.M. (Bruce), Ripatti, S. (Samuli), Teumer, A. (Alexander), Frayling, T.M. (Timothy), Metspalu, A. (Andres), Meurs, J.B.J. (Joyce) van, and Franke, L. (Lude)

Abstract

Identifying the downstream effects of disease-associated SNPs is challenging. To help overcome this problem, we performed expression quantitative trait locus (eQTL) meta-analysis in non-transformed peripheral blood samples from 5,311 individuals with replication in 2,775 individuals. We identified and replicated trans eQTLs for 233 SNPs (reflecting 103 independent loci) that were previously associated with complex traits at genome-wide significance. Some of these SNPs affect multiple genes in trans that are known to be altered in individuals with disease: rs4917014, previously associated with systemic lupus erythematosus (SLE), altered gene expression of C1QB and five type I interferon response genes, both hallmarks of SLE. DeepSAGE RNA sequencing showed that rs4917014 strongly alters the 3′ UTR levels of IKZF1 in cis, and chromatin immunoprecipitation and sequencing analysis of the trans-regulated genes implicated IKZF1 as the causal gene. Variants associated with cholesterol metabolism and type 1 diabetes showed similar phenomena, indicating that large-scale eQTL mapping provides insight into the downstream effects of many trait-associated variants.

Published
2013
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5. Cohort profile: The study of health in Pomerania

Author

Völzke, H. (Henry), Alte, D. (Dietrich), Schmidt, C.O. (Carsten Oliver), Radke, D. (Dörte), Lorbeer, R. (Roberto), Friedrich, N. (Nele), Aumann, N. (Nicole), Lau, K. (Katharina), Piontek, M. (Michael), Born, G. (Gabriele), Havemann, C. (Christoph), Ittermann, T. (Till), Schipf, S. (Sabine), Haring, R. (Robin), Baumeister, S.E. (Sebastian), Wallaschofski, H. (Henri), Nauck, M. (Matthias), Frick, S. (Stephanie), Arnold, A. (Andreas), Jünger, M. (Michael), Mayerle, J. (Julia), Kraft, M. (Matthias), Lerch, M.M. (Markus), Dörr, M. (Marcus), Reffelmann, T. (Thorsten), Empen, K. (Klaus), Felix, S.B. (Stephan), Obst, A. (Anne), Koch, B. (Beate), Gläser, S. (Sven), Ewert, R. (Ralf), Fietze, I. (Ingo), Penzel, T. (Thomas), Dören, M. (Martina), Rathmann, W. (Wolfgang), Haerting, J. (Johannes), Hannemann, M. (Mario), Röpcke, J. (Jürgen), Schminke, U. (Ulf), Jürgens, C. (Clemens), Tost, F. (Frank), Rettig, R. (Rainer), Kors, J.A. (Jan), Ungerer, S. (Saskia), Hegenscheid, K. (Katrin), Kühn, J.-P., Hosten, N. (Norbert), Puls, R. (Ralf), Henke, J. (Jörg), Gloger, O. (Oliver), Teumer, A. (Alexander), Homuth, G. (Georg), Völker, U. (Uwe), Schwahn, C. (Christian), Holtfreter, B. (Birte), Polzer, I. (Ines), Kohlmann, T. (Thomas), Grabe, H.J. (Hans Jörgen), Rosskopf, D. (Dieter), Kroemer, H.K. (Heyo), Kocher, T. (Thomas), Biffar, R. (Reiner), John, U. (Ulrich), Hoffmann, W. (Wolfgang), Völzke, H. (Henry), Alte, D. (Dietrich), Schmidt, C.O. (Carsten Oliver), Radke, D. (Dörte), Lorbeer, R. (Roberto), Friedrich, N. (Nele), Aumann, N. (Nicole), Lau, K. (Katharina), Piontek, M. (Michael), Born, G. (Gabriele), Havemann, C. (Christoph), Ittermann, T. (Till), Schipf, S. (Sabine), Haring, R. (Robin), Baumeister, S.E. (Sebastian), Wallaschofski, H. (Henri), Nauck, M. (Matthias), Frick, S. (Stephanie), Arnold, A. (Andreas), Jünger, M. (Michael), Mayerle, J. (Julia), Kraft, M. (Matthias), Lerch, M.M. (Markus), Dörr, M. (Marcus), Reffelmann, T. (Thorsten), Empen, K. (Klaus), Felix, S.B. (Stephan), Obst, A. (Anne), Koch, B. (Beate), Gläser, S. (Sven), Ewert, R. (Ralf), Fietze, I. (Ingo), Penzel, T. (Thomas), Dören, M. (Martina), Rathmann, W. (Wolfgang), Haerting, J. (Johannes), Hannemann, M. (Mario), Röpcke, J. (Jürgen), Schminke, U. (Ulf), Jürgens, C. (Clemens), Tost, F. (Frank), Rettig, R. (Rainer), Kors, J.A. (Jan), Ungerer, S. (Saskia), Hegenscheid, K. (Katrin), Kühn, J.-P., Hosten, N. (Norbert), Puls, R. (Ralf), Henke, J. (Jörg), Gloger, O. (Oliver), Teumer, A. (Alexander), Homuth, G. (Georg), Völker, U. (Uwe), Schwahn, C. (Christian), Holtfreter, B. (Birte), Polzer, I. (Ines), Kohlmann, T. (Thomas), Grabe, H.J. (Hans Jörgen), Rosskopf, D. (Dieter), Kroemer, H.K. (Heyo), Kocher, T. (Thomas), Biffar, R. (Reiner), John, U. (Ulrich), and Hoffmann, W. (Wolfgang)

Published
2011
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