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Modulation of Genet...
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Huffman, Jennifer E.
(author)
Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans
- Article/chapterEnglish2015
Publisher, publication year, extent ...
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2015-03-26
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Public Library of Science (PLoS),2015
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-258896
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-258896URI
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https://doi.org/10.1371/journal.pone.0119752DOI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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, P-inter= 2.6 x 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 x 10(-8)), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 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 (Pdifflean-obese= 2 x 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 obesogenic environment.
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Albrecht, Eva
(author)
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Teumer, Alexander
(author)
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Mangino, Massimo
(author)
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Kapur, Karen
(author)
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Johnson, Toby
(author)
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Kutalik, Zoltn
(author)
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Pirastu, Nicola
(author)
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Pistis, Giorgio
(author)
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Lopez, Lorna M.
(author)
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Haller, Toomas
(author)
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Salo, Perttu
(author)
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Goel, Anuj
(author)
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Li, Man
(author)
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Tanaka, Toshiko
(author)
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Dehghan, Abbas
(author)
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Ruggiero, Daniela
(author)
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Malerba, Giovanni
(author)
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Smith, Albert V.
(author)
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Nolte, Ilja M.
(author)
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Portas, Laura
(author)
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Phipps-Green, Amanda
(author)
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Boteva, Lora
(author)
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Navarro, Pau
(author)
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Johansson, ÅsaUppsala universitet,Medicinsk genetik och genomik,Uppsala kliniska forskningscentrum (UCR)(Swepub:uu)asjoh108
(author)
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Hicks, Andrew A.
(author)
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Polasek, Ozren
(author)
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Esko, Tonu
(author)
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Peden, John F.
(author)
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Harris, Sarah E.
(author)
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Murgia, Federico
(author)
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Wild, Sarah H.
(author)
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Tenesa, Albert
(author)
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Tin, Adrienne
(author)
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Mihailov, Evelin
(author)
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Grotevendt, Anne
(author)
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Gislason, Gauti K.
(author)
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Coresh, Josef
(author)
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D'Adamo, Pio
(author)
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Ulivi, Sheila
(author)
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Vollenweider, Peter
(author)
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Waeber, Gerard
(author)
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Campbell, Susan
(author)
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Kolcic, Ivana
(author)
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Fisher, Krista
(author)
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Viigimaa, Margus
(author)
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Metter, Jeffrey E.
(author)
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Masciullo, Corrado
(author)
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Trabetti, Elisabetta
(author)
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Bombieri, Cristina
(author)
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Sorice, Rossella
(author)
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Doering, Angela
(author)
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Reischl, Eva
(author)
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Strauch, Konstantin
(author)
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Hofman, Albert
(author)
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Uitterlinden, Andre G.
(author)
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Waldenberger, Melanie
(author)
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Wichmann, H-Erich
(author)
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Davies, Gail
(author)
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Gow, Alan J.
(author)
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Dalbeth, Nicola
(author)
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Stamp, Lisa
(author)
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Smit, Johannes H.
(author)
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Kirin, Mirna
(author)
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Nagaraja, Ramaiah
(author)
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Nauck, Matthias
(author)
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Schurmann, Claudia
(author)
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Budde, Kathrin
(author)
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Farrington, Susan M.
(author)
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Theodoratou, Evropi
(author)
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Jula, Antti
(author)
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Salomaa, Veikko
(author)
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Sala, Cinzia
(author)
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Hengstenberg, Christian
(author)
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Burnier, Michel
(author)
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Maegi, Reedik
(author)
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Klopp, Norman
(author)
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Kloiber, Stefan
(author)
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Schipf, Sabine
(author)
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Ripatti, Samuli
(author)
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Cabras, Stefano
(author)
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Soranzo, Nicole
(author)
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Homuth, Georg
(author)
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Nutile, Teresa
(author)
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Munroe, Patricia B.
(author)
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Hastie, Nicholas
(author)
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Campbell, Harry
(author)
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Rudan, Igor
(author)
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Cabrera, Claudia
(author)
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Haley, Chris
(author)
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Franco, Oscar H.
(author)
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Merriman, Tony R.
(author)
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Gudnason, Vilmundur
(author)
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Pirastu, Mario
(author)
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Penninx, Brenda W.
(author)
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Snieder, Harold
(author)
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Metspalu, Andres
(author)
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Ciullo, Marina
(author)
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Pramstaller, Peter P.
(author)
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van Duijn, Cornelia M.
(author)
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Ferrucci, Luigi
(author)
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Gambaro, Giovanni
(author)
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Deary, Ian J.
(author)
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Dunlop, Malcolm G.
(author)
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Wilson, James F.
(author)
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Gasparini, Paolo
(author)
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Gyllensten, UlfUppsala universitet,Medicinsk genetik och genomik(Swepub:uu)ulfgyll
(author)
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Spector, Tim D.
(author)
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Wright, Alan F.
(author)
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Hayward, Caroline
(author)
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Watkins, Hugh
(author)
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Perola, Markus
(author)
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Bochud, Murielle
(author)
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Kao, W. H. Linda
(author)
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Caulfield, Mark
(author)
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Toniolo, Daniela
(author)
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Voelzke, Henry
(author)
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Gieger, Christian
(author)
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Koettgen, Anna
(author)
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Vitart, Veronique
(author)
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Uppsala universitetMedicinsk genetik och genomik
(creator_code:org_t)
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Huffman, Jennife ...
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Albrecht, Eva
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Teumer, Alexande ...
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Mangino, Massimo
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Kapur, Karen
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Johnson, Toby
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show more...
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Kutalik, Zoltn
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Pirastu, Nicola
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Pistis, Giorgio
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Lopez, Lorna M.
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Haller, Toomas
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Salo, Perttu
-
Goel, Anuj
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Li, Man
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Tanaka, Toshiko
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Dehghan, Abbas
-
Ruggiero, Daniel ...
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Malerba, Giovann ...
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Smith, Albert V.
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Nolte, Ilja M.
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Portas, Laura
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Phipps-Green, Am ...
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Boteva, Lora
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Navarro, Pau
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Johansson, Åsa
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Hicks, Andrew A.
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Polasek, Ozren
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Esko, Tonu
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Peden, John F.
-
Harris, Sarah E.
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Murgia, Federico
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Wild, Sarah H.
-
Tenesa, Albert
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Tin, Adrienne
-
Mihailov, Evelin
-
Grotevendt, Anne
-
Gislason, Gauti ...
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Coresh, Josef
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D'Adamo, Pio
-
Ulivi, Sheila
-
Vollenweider, Pe ...
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Waeber, Gerard
-
Campbell, Susan
-
Kolcic, Ivana
-
Fisher, Krista
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Viigimaa, Margus
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Metter, Jeffrey ...
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Masciullo, Corra ...
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Trabetti, Elisab ...
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Bombieri, Cristi ...
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Sorice, Rossella
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Doering, Angela
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Reischl, Eva
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Strauch, Konstan ...
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Hofman, Albert
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Uitterlinden, An ...
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Waldenberger, Me ...
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Wichmann, H-Eric ...
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Davies, Gail
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Gow, Alan J.
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Dalbeth, Nicola
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Stamp, Lisa
-
Smit, Johannes H ...
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Kirin, Mirna
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Nagaraja, Ramaia ...
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Nauck, Matthias
-
Schurmann, Claud ...
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Budde, Kathrin
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Farrington, Susa ...
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Theodoratou, Evr ...
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Jula, Antti
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Salomaa, Veikko
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Sala, Cinzia
-
Hengstenberg, Ch ...
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Burnier, Michel
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Maegi, Reedik
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Klopp, Norman
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Kloiber, Stefan
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Schipf, Sabine
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Ripatti, Samuli
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Cabras, Stefano
-
Soranzo, Nicole
-
Homuth, Georg
-
Nutile, Teresa
-
Munroe, Patricia ...
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Hastie, Nicholas
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Campbell, Harry
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Rudan, Igor
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Cabrera, Claudia
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Haley, Chris
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Franco, Oscar H.
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Merriman, Tony R ...
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Gudnason, Vilmun ...
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Pirastu, Mario
-
Penninx, Brenda ...
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Snieder, Harold
-
Metspalu, Andres
-
Ciullo, Marina
-
Pramstaller, Pet ...
-
van Duijn, Corne ...
-
Ferrucci, Luigi
-
Gambaro, Giovann ...
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Deary, Ian J.
-
Dunlop, Malcolm ...
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Wilson, James F.
-
Gasparini, Paolo
-
Gyllensten, Ulf
-
Spector, Tim D.
-
Wright, Alan F.
-
Hayward, Carolin ...
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Watkins, Hugh
-
Perola, Markus
-
Bochud, Murielle
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Kao, W. H. Linda
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Caulfield, Mark
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Toniolo, Daniela
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Voelzke, Henry
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Gieger, Christia ...
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Koettgen, Anna
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Vitart, Veroniqu ...
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