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3 results on '"Fisher, K. (Krista)"'

1. DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases

Author

Wielscher, M. (Matthias), Mandaviya, P. R. (Pooja R.), Kuehnel, B. (Brigitte), Joehanes, R. (Roby), Mustafa, R. (Rima), Robinson, O. (Oliver), Zhang, Y. (Yan), Bodinier, B. (Barbara), Walton, E. (Esther), Mishra, P. P. (Pashupati P.), Schlosser, P. (Pascal), Wilson, R. (Rory), Tsai, P.-C. (Pei-Chien), Palaniswamy, S. (Saranya), Marioni, R. E. (Riccardo E.), Fiorito, G. (Giovanni), Cugliari, G. (Giovanni), Karhunen, V. (Ville), Ghanbari, M. (Mohsen), Psaty, B. M. (Bruce M.), Loh, M. (Marie), Bis, J. C. (Joshua C.), Lehne, B. (Benjamin), Sotoodehnia, N. (Nona), Deary, I. J. (Ian J.), Chadeau-Hyam, M. (Marc), Brody, J. A. (Jennifer A.), Cardona, A. (Alexia), Selvin, E. (Elizabeth), Smith, A. K. (Alicia K.), Miller, A. H. (Andrew H.), Torres, M. A. (Mylin A.), Marouli, E. (Eirini), Gao, X. (Xin), van Meurs, J. B. (Joyce B. J.), Graf-Schindler, J. (Johanna), Rathmann, W. (Wolfgang), Koenig, W. (Wolfgang), Peters, A. (Annette), Weninger, W. (Wolfgang), Farlik, M. (Matthias), Zhang, T. (Tao), Chen, W. (Wei), Xia, Y. (Yujing), Teumer, A. (Alexander), Nauck, M. (Matthias), Grabe, H. J. (Hans J.), Doerr, M. (Macus), Lehtimaki, T. (Terho), Guan, W. (Weihua), Milani, L. (Lili), Tanaka, T. (Toshiko), Fisher, K. (Krista), Waite, L. L. (Lindsay L.), Kasela, S. (Silva), Vineis, P. (Paolo), Verweij, N. (Niek), van der Harst, P. (Pim), Iacoviello, L. (Licia), Sacerdote, C. (Carlotta), Panico, S. (Salvatore), Krogh, V. (Vittorio), Tumino, R. (Rosario), Tzala, E. (Evangelia), Matullo, G. (Giuseppe), Hurme, M. A. (Mikko A.), Raitakari, O. T. (Olli T.), Colicino, E. (Elena), Baccarelli, A. A. (Andrea A.), Kahonen, M. (Mika), Herzig, K.-H. (Karl-Heinz), Li, S. (Shengxu), BIOS consortium, Conneely, K. N. (Karen N.), Kooner, J. S. (Jaspal S.), Kottgen, A. (Anna), Heijmans, B. T. (Bastiaan T.), Deloukas, P. (Panos), Relton, C. (Caroline), Ong, K. K. (Ken K.), Bell, J. T. (Jordana T.), Boerwinkle, E. (Eric), Elliott, P. (Paul), Brenner, H. (Hermann), Beekman, M. (Marian), Levy, D. (Daniel), Waldenberger, M. (Melanie), Chambers, J. C. (John C.), Dehghan, A. (Abbas), Järvelin, M.-R. (Marjo-Riitta), Wielscher, M. (Matthias), Mandaviya, P. R. (Pooja R.), Kuehnel, B. (Brigitte), Joehanes, R. (Roby), Mustafa, R. (Rima), Robinson, O. (Oliver), Zhang, Y. (Yan), Bodinier, B. (Barbara), Walton, E. (Esther), Mishra, P. P. (Pashupati P.), Schlosser, P. (Pascal), Wilson, R. (Rory), Tsai, P.-C. (Pei-Chien), Palaniswamy, S. (Saranya), Marioni, R. E. (Riccardo E.), Fiorito, G. (Giovanni), Cugliari, G. (Giovanni), Karhunen, V. (Ville), Ghanbari, M. (Mohsen), Psaty, B. M. (Bruce M.), Loh, M. (Marie), Bis, J. C. (Joshua C.), Lehne, B. (Benjamin), Sotoodehnia, N. (Nona), Deary, I. J. (Ian J.), Chadeau-Hyam, M. (Marc), Brody, J. A. (Jennifer A.), Cardona, A. (Alexia), Selvin, E. (Elizabeth), Smith, A. K. (Alicia K.), Miller, A. H. (Andrew H.), Torres, M. A. (Mylin A.), Marouli, E. (Eirini), Gao, X. (Xin), van Meurs, J. B. (Joyce B. J.), Graf-Schindler, J. (Johanna), Rathmann, W. (Wolfgang), Koenig, W. (Wolfgang), Peters, A. (Annette), Weninger, W. (Wolfgang), Farlik, M. (Matthias), Zhang, T. (Tao), Chen, W. (Wei), Xia, Y. (Yujing), Teumer, A. (Alexander), Nauck, M. (Matthias), Grabe, H. J. (Hans J.), Doerr, M. (Macus), Lehtimaki, T. (Terho), Guan, W. (Weihua), Milani, L. (Lili), Tanaka, T. (Toshiko), Fisher, K. (Krista), Waite, L. L. (Lindsay L.), Kasela, S. (Silva), Vineis, P. (Paolo), Verweij, N. (Niek), van der Harst, P. (Pim), Iacoviello, L. (Licia), Sacerdote, C. (Carlotta), Panico, S. (Salvatore), Krogh, V. (Vittorio), Tumino, R. (Rosario), Tzala, E. (Evangelia), Matullo, G. (Giuseppe), Hurme, M. A. (Mikko A.), Raitakari, O. T. (Olli T.), Colicino, E. (Elena), Baccarelli, A. A. (Andrea A.), Kahonen, M. (Mika), Herzig, K.-H. (Karl-Heinz), Li, S. (Shengxu), BIOS consortium, Conneely, K. N. (Karen N.), Kooner, J. S. (Jaspal S.), Kottgen, A. (Anna), Heijmans, B. T. (Bastiaan T.), Deloukas, P. (Panos), Relton, C. (Caroline), Ong, K. K. (Ken K.), Bell, J. T. (Jordana T.), Boerwinkle, E. (Eric), Elliott, P. (Paul), Brenner, H. (Hermann), Beekman, M. (Marian), Levy, D. (Daniel), Waldenberger, M. (Melanie), Chambers, J. C. (John C.), Dehghan, A. (Abbas), and Järvelin, M.-R. (Marjo-Riitta)

Abstract

We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.

Published
2022

2. Modulation of genetic associations with serum urate levels by body-mass-index in humans

Author

Huffman, J.E. (Jennifer), Albrecht, E. (Eva), Teumer, A. (Alexander), Mangino, M. (Massimo), Kapur, K. (Karen), Johnson, T. (Toby), Kutalik, Z. (Zoltán), Pirastu, N. (Nicola), Pistis, G. (Giorgio), Lopez, L.M. (Lorna), Haller, T. (Toomas), Salo, P. (Perttu), Goel, A. (Anuj), Li, M. (Man), Tanaka, T. (Toshiko), Dehghan, A. (Abbas), Ruggiero, D., Malerba, G. (Giovanni), Smith, A.V. (Albert Vernon), Nolte, I.M. (Ilja M.), Portas, L. (Laura), Phipps-Green, A. (Amanda), Boteva, L. (Lora), Navarro, P. (Pau), Johansson, A. (Åsa), Hicks, A.A. (Andrew), Polasek, O. (Ozren), Esko, T. (Tõnu), Peden, J. (John), Harris, S.E. (Sarah), Murgia, D. (Daniela), Wild, S.H. (Sarah H.), Tenesa, A. (Albert), Tin, A. (Adrienne), Mihailov, E. (Evelin), Grotevendt, A. (Anne), Gislason, G.K., Coresh, J. (Josef), Adamo, P. (Pio) d', Ulivi, S. (Shelia), Vollenweider, P. (Peter), Waeber, G. (Gérard), Campbell, S. (Susan), Kolcic, I. (Ivana), Fisher, K. (Krista), Viigimaa, M. (Margus), Metter, J.E. (Jeffrey E.), Masciullo, C. (Corrado), Trabetti, E. (Elisabetta), Bombieri, C. (Cristina), Sorice, R., Döring, A. (Angela), Reischl, G. (Gunilla), Strauch, K. (Konstantin), Hofman, A. (Albert), Uitterlinden, A.G. (André), Waldenberger, M. (Melanie), Wichmann, H.E. (Heinz Erich), Davies, G. (Gail), Gow, A.J. (Alan J.), Dalbeth, N. (Nicola), Stamp, L. (Lisa), Smit, J.H. (Johannes H.), Kirin, M. (Mirna), Nagaraja, R. (Ramaiah), Nauck, M. (Matthias), Schurmann, C. (Claudia), Budde, K. (Klemens), Farrington, S.M. (Susan), Theodoratou, E. (Evropi), Jula, A. (Antti), Salomaa, V. (Veikko), Sala, C. (Cinzia), Hengstenberg, C. (Christian), Burnier, M. (Michel), Mägi, R. (Reedik), Klopp, N. (Norman), Kloiber, S. (Stefan), Schipf, S. (Sabine), Ripatti, S. (Samuli), Cabras, S. (Stefano), Soranzo, N. (Nicole), Homuth, G. (Georg), Nutile, T., Munroe, P. (Patricia), Hastie, N. (Nick), Campbell, H. (H.), Rudan, I. (Igor), Cabrera, C. (Claudia), Haley, C. (Chris), Franco, O.H. (Oscar), Merriman, T.R. (Tony R.), Gudnason, V. (Vilmundur), Pirastu, M. (Mario), Penninx, B.W.J.H. (Brenda), Snieder, H. (Harold), Metspalu, A. (Andres), Ciullo, M., Pramstaller, P.P. (Peter Paul), Duijn, C.M. (Cornelia) van, Ferrucci, L. (Luigi), Gambaro, G. (Giovanni), Deary, I.J. (Ian J.), Dunlop, M.G. (Malcolm), Wilson, J.F. (James F), Gasparini, P. (Paolo), Gyllensten, U. (Ulf), Spector, T.D. (Timothy), Wright, A.F. (Alan), Hayward, C. (Caroline), Watkins, H. (Hugh), Perola, M. (Markus), Bochud, M. (Murielle), Kao, W.H.L. (Wen), Caulfield, M. (Mark), Toniolo, D. (Daniela), Völzke, H. (Henry), Gieger, C. (Christian), Köttgen, A. (Anna), Vitart, V. (Veronique), Huffman, J.E. (Jennifer), Albrecht, E. (Eva), Teumer, A. (Alexander), Mangino, M. (Massimo), Kapur, K. (Karen), Johnson, T. (Toby), Kutalik, Z. (Zoltán), Pirastu, N. (Nicola), Pistis, G. (Giorgio), Lopez, L.M. (Lorna), Haller, T. (Toomas), Salo, P. (Perttu), Goel, A. (Anuj), Li, M. (Man), Tanaka, T. (Toshiko), Dehghan, A. (Abbas), Ruggiero, D., Malerba, G. (Giovanni), Smith, A.V. (Albert Vernon), Nolte, I.M. (Ilja M.), Portas, L. (Laura), Phipps-Green, A. (Amanda), Boteva, L. (Lora), Navarro, P. (Pau), Johansson, A. (Åsa), Hicks, A.A. (Andrew), Polasek, O. (Ozren), Esko, T. (Tõnu), Peden, J. (John), Harris, S.E. (Sarah), Murgia, D. (Daniela), Wild, S.H. (Sarah H.), Tenesa, A. (Albert), Tin, A. (Adrienne), Mihailov, E. (Evelin), Grotevendt, A. (Anne), Gislason, G.K., Coresh, J. (Josef), Adamo, P. (Pio) d', Ulivi, S. (Shelia), Vollenweider, P. (Peter), Waeber, G. (Gérard), Campbell, S. (Susan), Kolcic, I. (Ivana), Fisher, K. (Krista), Viigimaa, M. (Margus), Metter, J.E. (Jeffrey E.), Masciullo, C. (Corrado), Trabetti, E. (Elisabetta), Bombieri, C. (Cristina), Sorice, R., Döring, A. (Angela), Reischl, G. (Gunilla), Strauch, K. (Konstantin), Hofman, A. (Albert), Uitterlinden, A.G. (André), Waldenberger, M. (Melanie), Wichmann, H.E. (Heinz Erich), Davies, G. (Gail), Gow, A.J. (Alan J.), Dalbeth, N. (Nicola), Stamp, L. (Lisa), Smit, J.H. (Johannes H.), Kirin, M. (Mirna), Nagaraja, R. (Ramaiah), Nauck, M. (Matthias), Schurmann, C. (Claudia), Budde, K. (Klemens), Farrington, S.M. (Susan), Theodoratou, E. (Evropi), Jula, A. (Antti), Salomaa, V. (Veikko), Sala, C. (Cinzia), Hengstenberg, C. (Christian), Burnier, M. (Michel), Mägi, R. (Reedik), Klopp, N. (Norman), Kloiber, S. (Stefan), Schipf, S. (Sabine), Ripatti, S. (Samuli), Cabras, S. (Stefano), Soranzo, N. (Nicole), Homuth, G. (Georg), Nutile, T., Munroe, P. (Patricia), Hastie, N. (Nick), Campbell, H. (H.), Rudan, I. (Igor), Cabrera, C. (Claudia), Haley, C. (Chris), Franco, O.H. (Oscar), Merriman, T.R. (Tony R.), Gudnason, V. (Vilmundur), Pirastu, M. (Mario), Penninx, B.W.J.H. (Brenda), Snieder, H. (Harold), Metspalu, A. (Andres), Ciullo, M., Pramstaller, P.P. (Peter Paul), Duijn, C.M. (Cornelia) van, Ferrucci, L. (Luigi), Gambaro, G. (Giovanni), Deary, I.J. (Ian J.), Dunlop, M.G. (Malcolm), Wilson, J.F. (James F), Gasparini, P. (Paolo), Gyllensten, U. (Ulf), Spector, T.D. (Timothy), Wright, A.F. (Alan), Hayward, C. (Caroline), Watkins, H. (Hugh), Perola, M. (Markus), Bochud, M. (Murielle), Kao, W.H.L. (Wen), Caulfield, M. (Mark), Toniolo, D. (Daniela), Völzke, H. (Henry), Gieger, C. (Christian), Köttgen, A. (Anna), and Vitart, V. (Veronique)

Abstract

We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 × 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDAR-ADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 × 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight = 9.1 × 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (P difflean-obese= 2 × 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obsogenic environment.

Published
2015
Full Text
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3. Modulation of genetic associations with serum urate levels by body-mass-index in humans

Author

Huffman, J.E. (Jennifer), Albrecht, E. (Eva), Teumer, A. (Alexander), Mangino, M. (Massimo), Kapur, K. (Karen), Johnson, T. (Toby), Kutalik, Z. (Zoltán), Pirastu, N. (Nicola), Pistis, G. (Giorgio), Lopez, L.M. (Lorna), Haller, T. (Toomas), Salo, P. (Perttu), Goel, A. (Anuj), Li, M. (Man), Tanaka, T. (Toshiko), Dehghan, A. (Abbas), Ruggiero, D., Malerba, G. (Giovanni), Smith, A.V. (Albert Vernon), Nolte, I.M. (Ilja M.), Portas, L. (Laura), Phipps-Green, A. (Amanda), Boteva, L. (Lora), Navarro, P. (Pau), Johansson, A. (Åsa), Hicks, A.A. (Andrew), Polasek, O. (Ozren), Esko, T. (Tõnu), Peden, J. (John), Harris, S.E. (Sarah), Murgia, D. (Daniela), Wild, S.H. (Sarah H.), Tenesa, A. (Albert), Tin, A. (Adrienne), Mihailov, E. (Evelin), Grotevendt, A. (Anne), Gislason, G.K., Coresh, J. (Josef), Adamo, P. (Pio) d', Ulivi, S. (Shelia), Vollenweider, P. (Peter), Waeber, G. (Gérard), Campbell, S. (Susan), Kolcic, I. (Ivana), Fisher, K. (Krista), Viigimaa, M. (Margus), Metter, J.E. (Jeffrey E.), Masciullo, C. (Corrado), Trabetti, E. (Elisabetta), Bombieri, C. (Cristina), Sorice, R., Döring, A. (Angela), Reischl, G. (Gunilla), Strauch, K. (Konstantin), Hofman, A. (Albert), Uitterlinden, A.G. (André), Waldenberger, M. (Melanie), Wichmann, H.E. (Heinz Erich), Davies, G. (Gail), Gow, A.J. (Alan J.), Dalbeth, N. (Nicola), Stamp, L. (Lisa), Smit, J.H. (Johannes H.), Kirin, M. (Mirna), Nagaraja, R. (Ramaiah), Nauck, M. (Matthias), Schurmann, C. (Claudia), Budde, K. (Klemens), Farrington, S.M. (Susan), Theodoratou, E. (Evropi), Jula, A. (Antti), Salomaa, V. (Veikko), Sala, C. (Cinzia), Hengstenberg, C. (Christian), Burnier, M. (Michel), Mägi, R. (Reedik), Klopp, N. (Norman), Kloiber, S. (Stefan), Schipf, S. (Sabine), Ripatti, S. (Samuli), Cabras, S. (Stefano), Soranzo, N. (Nicole), Homuth, G. (Georg), Nutile, T., Munroe, P. (Patricia), Hastie, N. (Nick), Campbell, H. (H.), Rudan, I. (Igor), Cabrera, C. (Claudia), Haley, C. (Chris), Franco, O.H. (Oscar), Merriman, T.R. (Tony R.), Gudnason, V. (Vilmundur), Pirastu, M. (Mario), Penninx, B.W.J.H. (Brenda), Snieder, H. (Harold), Metspalu, A. (Andres), Ciullo, M., Pramstaller, P.P. (Peter Paul), Duijn, C.M. (Cornelia) van, Ferrucci, L. (Luigi), Gambaro, G. (Giovanni), Deary, I.J. (Ian J.), Dunlop, M.G. (Malcolm), Wilson, J.F. (James F), Gasparini, P. (Paolo), Gyllensten, U. (Ulf), Spector, T.D. (Timothy), Wright, A.F. (Alan), Hayward, C. (Caroline), Watkins, H. (Hugh), Perola, M. (Markus), Bochud, M. (Murielle), Kao, W.H.L. (Wen), Caulfield, M. (Mark), Toniolo, D. (Daniela), Völzke, H. (Henry), Gieger, C. (Christian), Köttgen, A. (Anna), Vitart, V. (Veronique), Huffman, J.E. (Jennifer), Albrecht, E. (Eva), Teumer, A. (Alexander), Mangino, M. (Massimo), Kapur, K. (Karen), Johnson, T. (Toby), Kutalik, Z. (Zoltán), Pirastu, N. (Nicola), Pistis, G. (Giorgio), Lopez, L.M. (Lorna), Haller, T. (Toomas), Salo, P. (Perttu), Goel, A. (Anuj), Li, M. (Man), Tanaka, T. (Toshiko), Dehghan, A. (Abbas), Ruggiero, D., Malerba, G. (Giovanni), Smith, A.V. (Albert Vernon), Nolte, I.M. (Ilja M.), Portas, L. (Laura), Phipps-Green, A. (Amanda), Boteva, L. (Lora), Navarro, P. (Pau), Johansson, A. (Åsa), Hicks, A.A. (Andrew), Polasek, O. (Ozren), Esko, T. (Tõnu), Peden, J. (John), Harris, S.E. (Sarah), Murgia, D. (Daniela), Wild, S.H. (Sarah H.), Tenesa, A. (Albert), Tin, A. (Adrienne), Mihailov, E. (Evelin), Grotevendt, A. (Anne), Gislason, G.K., Coresh, J. (Josef), Adamo, P. (Pio) d', Ulivi, S. (Shelia), Vollenweider, P. (Peter), Waeber, G. (Gérard), Campbell, S. (Susan), Kolcic, I. (Ivana), Fisher, K. (Krista), Viigimaa, M. (Margus), Metter, J.E. (Jeffrey E.), Masciullo, C. (Corrado), Trabetti, E. (Elisabetta), Bombieri, C. (Cristina), Sorice, R., Döring, A. (Angela), Reischl, G. (Gunilla), Strauch, K. (Konstantin), Hofman, A. (Albert), Uitterlinden, A.G. (André), Waldenberger, M. (Melanie), Wichmann, H.E. (Heinz Erich), Davies, G. (Gail), Gow, A.J. (Alan J.), Dalbeth, N. (Nicola), Stamp, L. (Lisa), Smit, J.H. (Johannes H.), Kirin, M. (Mirna), Nagaraja, R. (Ramaiah), Nauck, M. (Matthias), Schurmann, C. (Claudia), Budde, K. (Klemens), Farrington, S.M. (Susan), Theodoratou, E. (Evropi), Jula, A. (Antti), Salomaa, V. (Veikko), Sala, C. (Cinzia), Hengstenberg, C. (Christian), Burnier, M. (Michel), Mägi, R. (Reedik), Klopp, N. (Norman), Kloiber, S. (Stefan), Schipf, S. (Sabine), Ripatti, S. (Samuli), Cabras, S. (Stefano), Soranzo, N. (Nicole), Homuth, G. (Georg), Nutile, T., Munroe, P. (Patricia), Hastie, N. (Nick), Campbell, H. (H.), Rudan, I. (Igor), Cabrera, C. (Claudia), Haley, C. (Chris), Franco, O.H. (Oscar), Merriman, T.R. (Tony R.), Gudnason, V. (Vilmundur), Pirastu, M. (Mario), Penninx, B.W.J.H. (Brenda), Snieder, H. (Harold), Metspalu, A. (Andres), Ciullo, M., Pramstaller, P.P. (Peter Paul), Duijn, C.M. (Cornelia) van, Ferrucci, L. (Luigi), Gambaro, G. (Giovanni), Deary, I.J. (Ian J.), Dunlop, M.G. (Malcolm), Wilson, J.F. (James F), Gasparini, P. (Paolo), Gyllensten, U. (Ulf), Spector, T.D. (Timothy), Wright, A.F. (Alan), Hayward, C. (Caroline), Watkins, H. (Hugh), Perola, M. (Markus), Bochud, M. (Murielle), Kao, W.H.L. (Wen), Caulfield, M. (Mark), Toniolo, D. (Daniela), Völzke, H. (Henry), Gieger, C. (Christian), Köttgen, A. (Anna), and Vitart, V. (Veronique)

Abstract

We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 × 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDAR-ADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 × 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight = 9.1 × 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (P difflean-obese= 2 × 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obsogenic environment.

Published
2015
Full Text
View/download PDF

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