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dc.contributor.authorPalmer, Nicholette D
dc.contributor.authorMcDonough, Caitrin W
dc.contributor.authorHicks, Pamela J
dc.contributor.authorRoh, Bong H
dc.contributor.authorWing, Maria R
dc.contributor.authorAn, S Sandy
dc.contributor.authorHester, Jessica M
dc.contributor.authorCooke, Jessica N
dc.contributor.authorBostrom, Meredith A
dc.contributor.authorRudock, Megan E
dc.contributor.authorTalbert, Matthew E
dc.contributor.authorLewis, Joshua P
dc.contributor.authorFerrara, Assiamira
dc.contributor.authorLu, Lingyi
dc.contributor.authorZiegler, Julie T
dc.contributor.authorSale, Michele M
dc.contributor.authorDivers, Jasmin
dc.contributor.authorShriner, Daniel
dc.contributor.authorAdeyemo, Adebowale
dc.contributor.authorRotimi, Charles N
dc.contributor.authorNg, Maggie C Y
dc.contributor.authorLangefeld, Carl D
dc.contributor.authorFreedman, Barry I
dc.contributor.authorBowden, Donald W
dc.contributor.authorVoight, Benjamin F
dc.contributor.authorScott, Laura J
dc.contributor.authorSteinthorsdottir, Valgerdur
dc.contributor.authorMorris, Andrew P
dc.contributor.authorDina, Christian
dc.contributor.authorWelch, Ryan P
dc.contributor.authorZeggini, Eleftheria
dc.contributor.authorHuth, Cornelia
dc.contributor.authorAulchenko, Yurii S
dc.contributor.authorThorleifsson, Gudmar
dc.contributor.authorMcCulloch, Laura J
dc.contributor.authorFerreira, Teresa
dc.contributor.authorGrallert, Harald
dc.contributor.authorAmin, Najaf
dc.contributor.authorWu, Guanming
dc.contributor.authorWiller, Cristen J
dc.contributor.authorRaychaudhuri, Soumya
dc.contributor.authorMcCarroll, Steve A
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorHofmann, Oliver M
dc.contributor.authorDupuis, Josée
dc.contributor.authorQi, Lu
dc.contributor.authorSegrè, Ayellet V
dc.contributor.authorvan Hoek, Mandy
dc.contributor.authorNavarro, Pau
dc.contributor.authorArdlie, Kristin
dc.contributor.authorBalkau, Beverley
dc.contributor.authorBenediktsson, Rafn
dc.contributor.authorBennett, Amanda J
dc.contributor.authorBlagieva, Roza
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorBonnycastle, Lori L
dc.contributor.authorBoström, Kristina Bengtsson
dc.contributor.authorBravenboer, Bert
dc.contributor.authorBumpstead, Suzannah
dc.contributor.authorBurtt, Noël P
dc.contributor.authorCharpentier, Guillaume
dc.contributor.authorChines, Peter S
dc.contributor.authorCornelis, Marilyn
dc.contributor.authorCouper, David J
dc.contributor.authorCrawford, Gabe
dc.contributor.authorDoney, Alex S F
dc.contributor.authorElliott, Katherine S
dc.contributor.authorElliott, Amanda L
dc.contributor.authorErdos, Michael R
dc.contributor.authorFox, Caroline S
dc.contributor.authorFranklin, Christopher S
dc.contributor.authorGanser, Martha
dc.contributor.authorGieger, Christian
dc.contributor.authorGrarup, Niels
dc.contributor.authorGreen, Todd
dc.contributor.authorGriffin, Simon
dc.contributor.authorGroves, Christopher J
dc.contributor.authorGuiducci, Candace
dc.contributor.authorHadjadj, Samy
dc.contributor.authorHassanali, Neelam
dc.contributor.authorHerder, Christian
dc.contributor.authorIsomaa, Bo
dc.contributor.authorJackson, Anne U
dc.contributor.authorJohnson, Paul R V
dc.contributor.authorJørgensen, Torben
dc.contributor.authorKao, Wen H L
dc.contributor.authorKlopp, Norman
dc.contributor.authorKong, Augustine
dc.contributor.authorKraft, Peter
dc.contributor.authorKuusisto, Johanna
dc.contributor.authorLauritzen, Torsten
dc.contributor.authorLi, Man
dc.contributor.authorLieverse, Aloysius
dc.contributor.authorLindgren, Cecilia M
dc.contributor.authorLyssenko, Valeriya
dc.contributor.authorMarre, Michel
dc.contributor.authorMeitinger, Thomas
dc.contributor.authorMidthjell, Kristian
dc.contributor.authorMorken, Mario A
dc.contributor.authorNarisu, Narisu
dc.contributor.authorNilsson, Peter
dc.contributor.authorOwen, Katharine R
dc.contributor.authorPayne, Felicity
dc.contributor.authorPerry, John R B
dc.contributor.authorPetersen, Ann-Kristin
dc.contributor.authorPlatou, Carl
dc.contributor.authorProença, Christine
dc.contributor.authorProkopenko, Inga
dc.contributor.authorRathmann, Wolfgang
dc.contributor.authorRayner, N William
dc.contributor.authorRobertson, Neil R
dc.contributor.authorRocheleau, Ghislain
dc.contributor.authorRoden, Michael
dc.contributor.authorSampson, Michael J
dc.contributor.authorSaxena, Richa
dc.contributor.authorShields, Beverley M
dc.contributor.authorShrader, Peter
dc.contributor.authorSigurdsson, Gunnar
dc.contributor.authorSparsø, Thomas
dc.contributor.authorStrassburger, Klaus
dc.contributor.authorStringham, Heather M
dc.contributor.authorSun, Qi
dc.contributor.authorSwift, Amy J
dc.contributor.authorThorand, Barbara
dc.contributor.authorTichet, Jean
dc.contributor.authorTuomi, Tiinamaija
dc.contributor.authorvan Dam, Rob M
dc.contributor.authorvan Haeften, Timon W
dc.contributor.authorvan Herpt, Thijs
dc.contributor.authorvan Vliet-Ostaptchouk, Jana V
dc.contributor.authorWalters, G Bragi
dc.contributor.authorWeedon, Michael N
dc.contributor.authorWijmenga, Cisca
dc.contributor.authorWitteman, Jacqueline
dc.contributor.authorBergman, Richard N
dc.contributor.authorCauchi, Stephane
dc.contributor.authorCollins, Francis S
dc.contributor.authorGloyn, Anna L
dc.contributor.authorGyllensten, Ulf
dc.contributor.authorHansen, Torben
dc.contributor.authorHide, Winston A
dc.contributor.authorHitman, Graham A
dc.contributor.authorHofman, Albert
dc.contributor.authorHunter, David J
dc.contributor.authorHveem, Kristian
dc.contributor.authorLaakso, Markku
dc.contributor.authorMohlke, Karen L
dc.contributor.authorMorris, Andrew D
dc.contributor.authorPalmer, Colin N A
dc.contributor.authorPramstaller, Peter P
dc.contributor.authorRudan, Igor
dc.contributor.authorSijbrands, Eric
dc.contributor.authorStein, Lincoln D
dc.contributor.authorTuomilehto, Jaakko
dc.contributor.authorUitterlinden, Andre
dc.contributor.authorWalker, Mark
dc.contributor.authorWareham, Nicholas J
dc.contributor.authorWatanabe, Richard M
dc.contributor.authorAbecasis, Goncalo R
dc.contributor.authorBoehm, Bernhard O
dc.contributor.authorCampbell, Harry
dc.contributor.authorDaly, Mark J
dc.contributor.authorHattersley, Andrew T
dc.contributor.authorHu, Frank B
dc.contributor.authorMeigs, James B
dc.contributor.authorPankow, James S
dc.contributor.authorPedersen, Oluf
dc.contributor.authorWichmann, H-Erich
dc.contributor.authorBarroso, Inês
dc.contributor.authorFlorez, Jose C
dc.contributor.authorFrayling, Timothy M
dc.contributor.authorGroop, Leif
dc.contributor.authorSladek, Rob
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorWilson, James F
dc.contributor.authorIllig, Thomas
dc.contributor.authorFroguel, Philippe
dc.contributor.authorvan Duijn, Cornelia M
dc.contributor.authorStefansson, Kari
dc.contributor.authorAltshuler, David
dc.contributor.authorBoehnke, Michael
dc.contributor.authorMcCarthy, Mark I
dc.contributor.authorSoranzo, Nicole
dc.contributor.authorWheeler, Eleanor
dc.contributor.authorGlazer, Nicole L
dc.contributor.authorBouatia-Naji, Nabila
dc.contributor.authorMägi, Reedik
dc.contributor.authorRandall, Joshua
dc.contributor.authorJohnson, Toby
dc.contributor.authorElliott, Paul
dc.contributor.authorRybin, Denis
dc.contributor.authorHenneman, Peter
dc.contributor.authorDehghan, Abbas
dc.contributor.authorHottenga, Jouke Jan
dc.contributor.authorSong, Kijoung
dc.contributor.authorGoel, Anuj
dc.contributor.authorEgan, Josephine M
dc.contributor.authorLajunen, Taina
dc.contributor.authorDoney, Alex
dc.contributor.authorKanoni, Stavroula
dc.contributor.authorCavalcanti-Proença, Christine
dc.contributor.authorKumari, Meena
dc.contributor.authorTimpson, Nicholas J
dc.contributor.authorZabena, Carina
dc.contributor.authorIngelsson, Erik
dc.contributor.authorAn, Ping
dc.contributor.authorO'Connell, Jeffrey
dc.contributor.authorLuan, Jian'an
dc.contributor.authorElliott, Amanda
dc.contributor.authorMcCarroll, Steven A
dc.contributor.authorRoccasecca, Rosa Maria
dc.contributor.authorPattou, François
dc.contributor.authorSethupathy, Praveen
dc.contributor.authorAriyurek, Yavuz
dc.contributor.authorBarter, Philip
dc.contributor.authorBeilby, John P
dc.contributor.authorBen-Shlomo, Yoav
dc.contributor.authorBergmann, Sven
dc.contributor.authorBochud, Murielle
dc.contributor.authorBonnefond, Amélie
dc.contributor.authorBorch-Johnsen, Knut
dc.contributor.authorBöttcher, Yvonne
dc.contributor.authorBrunner, Eric
dc.contributor.authorBumpstead, Suzannah J
dc.contributor.authorChen, Yii-Der Ida
dc.contributor.authorChines, Peter
dc.contributor.authorClarke, Robert
dc.contributor.authorCoin, Lachlan J M
dc.contributor.authorCooper, Matthew N
dc.contributor.authorCrisponi, Laura
dc.contributor.authorDay, Ian N M
dc.contributor.authorde Geus, Eco J C
dc.contributor.authorDelplanque, Jerome
dc.contributor.authorFedson, Annette C
dc.contributor.authorFischer-Rosinsky, Antje
dc.contributor.authorForouhi, Nita G
dc.contributor.authorFrants, Rune
dc.contributor.authorFranzosi, Maria Grazia
dc.contributor.authorGalan, Pilar
dc.contributor.authorGoodarzi, Mark O
dc.contributor.authorGraessler, Jürgen
dc.contributor.authorGrundy, Scott
dc.contributor.authorGwilliam, Rhian
dc.contributor.authorHallmans, Göran
dc.contributor.authorHammond, Naomi
dc.contributor.authorHan, Xijing
dc.contributor.authorHartikainen, Anna-Liisa
dc.contributor.authorHayward, Caroline
dc.contributor.authorHeath, Simon C
dc.contributor.authorHercberg, Serge
dc.contributor.authorHicks, Andrew A
dc.contributor.authorHillman, David R
dc.contributor.authorHingorani, Aroon D
dc.contributor.authorHui, Jennie
dc.contributor.authorHung, Joe
dc.contributor.authorJula, Antti
dc.contributor.authorKaakinen, Marika
dc.contributor.authorKaprio, Jaakko
dc.contributor.authorKesaniemi, Y Antero
dc.contributor.authorKivimaki, Mika
dc.contributor.authorKnight, Beatrice
dc.contributor.authorKoskinen, Seppo
dc.contributor.authorKovacs, Peter
dc.contributor.authorKyvik, Kirsten Ohm
dc.contributor.authorLathrop, G Mark
dc.contributor.authorLawlor, Debbie A
dc.contributor.authorLe Bacquer, Olivier
dc.contributor.authorLecoeur, Cécile
dc.contributor.authorLi, Yun
dc.contributor.authorMahley, Robert
dc.contributor.authorMangino, Massimo
dc.contributor.authorManning, Alisa K
dc.contributor.authorMartínez-Larrad, María Teresa
dc.contributor.authorMcAteer, Jarred B
dc.contributor.authorMcPherson, Ruth
dc.contributor.authorMeisinger, Christa
dc.contributor.authorMelzer, David
dc.contributor.authorMeyre, David
dc.contributor.authorMitchell, Braxton D
dc.contributor.authorMukherjee, Sutapa
dc.contributor.authorNaitza, Silvia
dc.contributor.authorNeville, Matthew J
dc.contributor.authorOostra, Ben A
dc.contributor.authorOrrù, Marco
dc.contributor.authorPakyz, Ruth
dc.contributor.authorPaolisso, Giuseppe
dc.contributor.authorPattaro, Cristian
dc.contributor.authorPearson, Daniel
dc.contributor.authorPeden, John F
dc.contributor.authorPedersen, Nancy L
dc.contributor.authorPerola, Markus
dc.contributor.authorPfeiffer, Andreas F H
dc.contributor.authorPichler, Irene
dc.contributor.authorPolasek, Ozren
dc.contributor.authorPosthuma, Danielle
dc.contributor.authorPotter, Simon C
dc.contributor.authorPouta, Anneli
dc.contributor.authorProvince, Michael A
dc.contributor.authorPsaty, Bruce M
dc.contributor.authorRayner, Nigel W
dc.contributor.authorRice, Kenneth
dc.contributor.authorRipatti, Samuli
dc.contributor.authorRivadeneira, Fernando
dc.contributor.authorRolandsson, Olov
dc.contributor.authorSandbaek, Annelli
dc.contributor.authorSandhu, Manjinder
dc.contributor.authorSanna, Serena
dc.contributor.authorSayer, Avan Aihie
dc.contributor.authorScheet, Paul
dc.contributor.authorSeedorf, Udo
dc.contributor.authorSharp, Stephen J
dc.contributor.authorShields, Beverley
dc.contributor.authorSijbrands, Eric J G
dc.contributor.authorSilveira, Angela
dc.contributor.authorSimpson, Laila
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dc.contributor.authorSmith, Nicholas L
dc.contributor.authorSovio, Ulla
dc.contributor.authorSwift, Amy
dc.contributor.authorSyddall, Holly
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dc.contributor.authorTanaka, Toshiko
dc.contributor.authorTönjes, Anke
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dc.contributor.authorWagner, Peter J
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dc.contributor.authorZhao, Jing Hua
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dc.contributor.authorBorecki, Ingrid B
dc.contributor.authorLoos, Ruth J F
dc.contributor.authorMeneton, Pierre
dc.contributor.authorMagnusson, Patrik K E
dc.contributor.authorNathan, David M
dc.contributor.authorWilliams, Gordon H
dc.contributor.authorSilander, Kaisa
dc.contributor.authorSalomaa, Veikko
dc.contributor.authorSmith, George Davey
dc.contributor.authorBornstein, Stefan R
dc.contributor.authorSchwarz, Peter
dc.contributor.authorSpranger, Joachim
dc.contributor.authorKarpe, Fredrik
dc.contributor.authorShuldiner, Alan R
dc.contributor.authorCooper, Cyrus
dc.contributor.authorDedoussis, George V
dc.contributor.authorSerrano-Ríos, Manuel
dc.contributor.authorLind, Lars
dc.contributor.authorPalmer, Lyle J
dc.contributor.authorFranks, Paul W
dc.contributor.authorEbrahim, Shah
dc.contributor.authorMarmot, Michael
dc.contributor.authorKao, W H Linda
dc.contributor.authorPramstaller, Peter Paul
dc.contributor.authorWright, Alan F
dc.contributor.authorStumvoll, Michael
dc.contributor.authorHamsten, Anders
dc.contributor.authorBuchanan, Thomas A
dc.contributor.authorValle, Timo T
dc.contributor.authorRotter, Jerome I
dc.contributor.authorSiscovick, David S
dc.contributor.authorPenninx, Brenda W J H
dc.contributor.authorBoomsma, Dorret I
dc.contributor.authorDeloukas, Panos
dc.contributor.authorSpector, Timothy D
dc.contributor.authorFerrucci, Luigi
dc.contributor.authorCao, Antonio
dc.contributor.authorScuteri, Angelo
dc.contributor.authorSchlessinger, David
dc.contributor.authorUda, Manuela
dc.contributor.authorRuokonen, Aimo
dc.contributor.authorJarvelin, Marjo-Riitta
dc.contributor.authorWaterworth, Dawn M
dc.contributor.authorVollenweider, Peter
dc.contributor.authorPeltonen, Leena
dc.contributor.authorMooser, Vincent
dc.contributor.authorSladek, Robert
dc.date.accessioned2013-09-03T10:55:45Z
dc.date.available2013-09-03T10:55:45Z
dc.date.issued2012
dc.identifier.citationPLoS ONE 2012, 7(1):e29202en_GB
dc.identifier.issn1932-6203
dc.identifier.pmid22238593
dc.identifier.doi10.1371/journal.pone.0029202
dc.identifier.urihttp://hdl.handle.net/2336/300672
dc.descriptionTo access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.en_GB
dc.description.abstractAfrican Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
dc.description.sponsorshipNational Institutes of Health HHSC268200782096C K99 DK081350 R01 DK066358 R01 DK053591 R01 HL56266 R01 DK070941 Wake Forest University School of Medicine M01 RR07122en_GB
dc.language.isoenen
dc.relation.urlhttp://dx.doi.org/10.1371/journal.pone.0029202en_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251563/en_GB
dc.rightsArchived with thanks to PloS oneen_GB
dc.subject.meshAdulten_GB
dc.subject.meshAfrican Americansen_GB
dc.subject.meshAgeden_GB
dc.subject.meshCase-Control Studiesen_GB
dc.subject.meshCohort Studiesen_GB
dc.subject.meshDiabetes Mellitus, Type 2en_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGenetic Predisposition to Diseaseen_GB
dc.subject.meshGenome-Wide Association Studyen_GB
dc.subject.meshGenotypeen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMeta-Analysis as Topicen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshPolymorphism, Single Nucleotideen_GB
dc.subject.meshValidation Studies as Topicen_GB
dc.titleA genome-wide association search for type 2 diabetes genes in African Americans.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America. nallred@wfubmc.eduen_GB
dc.identifier.journalPloS oneen_GB
dc.rights.accessOpen Access - Opinn aðganguren
html.description.abstractAfrican Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.


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