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Author Gaulton, K.J.; Ferreira, T.; Lee, Y.; Raimondo, A.; Magi, R.; Reschen, M.E.; Mahajan, A.; Locke, A.; William Rayner, N.; Robertson, N.; Scott, R.A.; Prokopenko, I.; Scott, L.J.; Green, T.; Sparso, T.; Thuillier, D.; Yengo, L.; Grallert, H.; Wahl, S.; Franberg, M.; Strawbridge, R.J.; Kestler, H.; Chheda, H.; Eisele, L.; Gustafsson, S.; Steinthorsdottir, V.; Thorleifsson, G.; Qi, L.; Karssen, L.C.; van Leeuwen, E.M.; Willems, S.M.; Li, M.; Chen, H.; Fuchsberger, C.; Kwan, P.; Ma, C.; Linderman, M.; Lu, Y.; Thomsen, S.K.; Rundle, J.K.; Beer, N.L.; van de Bunt, M.; Chalisey, A.; Kang, H.M.; Voight, B.F.; Abecasis, G.R.; Almgren, P.; Baldassarre, D.; Balkau, B.; Benediktsson, R.; Bluher, M.; Boeing, H.; Bonnycastle, L.L.; Bottinger, E.P.; Burtt, N.P.; Carey, J.; Charpentier, G.; Chines, P.S.; Cornelis, M.C.; Couper, D.J.; Crenshaw, A.T.; van Dam, R.M.; Doney, A.S.; Dorkhan, M.; Edkins, S.; Eriksson, J.G.; Esko, T.; Eury, E.; Fadista, J.; Flannick, J.; Fontanillas, P.; Fox, C.; Franks, P.W.; Gertow, K.; Gieger, C.; Gigante, B.; Gottesman, O.; Grant, G.B.; Grarup, N.; Groves, C.J.; Hassinen, M.; Have, C.T.; Herder, C.; Holmen, O.L.; Hreidarsson, A.B.; Humphries, S.E.; Hunter, D.J.; Jackson, A.U.; Jonsson, A.; Jorgensen, M.E.; Jorgensen, T.; Kao, W.H.; Kerrison, N.D.; Kinnunen, L.; Klopp, N.; Kong, A.; Kovacs, P.; Kraft, P.; Kravic, J.; Langford, C.; Leander, K.; Liang, L.; Lichtner, P.; Lindgren, C.M.; Lindholm, E.; Linneberg, A.; Liu, C.T.; Lobbens, S.; Luan, J.; Lyssenko, V.; Mannisto, S.; McLeod, O.; Meyer, J.; Mihailov, E.; Mirza, G.; Muhleisen, T.W.; Muller-Nurasyid, M.; Navarro, C.; Nothen, M.M.; Oskolkov, N.N.; Owen, K.R.; Palli, D.; Pechlivanis, S.; Peltonen, L.; Perry, J.R.; Platou, C.G.; Roden, M.; Ruderfer, D.; Rybin, D.; van der Schouw, Y.T.; Sennblad, B.; Sigurethsson, G.; Stancakova, A.; Steinbach, G.; Storm, P.; Strauch, K.; Stringham, H.M.; Sun, Q.; Thorand, B.; Tikkanen, E.; Tonjes, A.; Trakalo, J.; Tremoli, E.; Tuomi, T.; Wennauer, R.; Wiltshire, S.; Wood, A.R.; Zeggini, E.; Dunham, I.; Birney, E.; Pasquali, L.; Ferrer, J.; Loos, R.J.; Dupuis, J.; Florez, J.C.; Boerwinkle, E.; Pankow, J.S.; van Duijn, C.; Sijbrands, E.; Meigs, J.B.; Hu, F.B.; Thorsteinsdottir, U.; Stefansson, K.; Lakka, T.A.; Rauramaa, R.; Stumvoll, M.; Pedersen, N.L.; Lind, L.; Keinanen-Kiukaanniemi, S.M.; Korpi-Hyovalti, E.; Saaristo, T.E.; Saltevo, J.; Kuusisto, J.; Laakso, M.; Metspalu, A.; Erbel, R.; Jocke, K.H.; Moebus, S.; Ripatti, S.; Salomaa, V.; Ingelsson, E.; Boehm, B.O.; Bergman, R.N.; Collins, F.S.; Mohlke, K.L.; Koistinen, H.; Tuomilehto, J.; Hveem, K.; Njolstad, I.; Deloukas, P.; Donnelly, P.J.; Frayling, T.M.; Hattersley, A.T.; de Faire, U.; Hamsten, A.; Illig, T.; Peters, A.; Cauchi, S.; Sladek, R.; Froguel, P.; Hansen, T.; Pedersen, O.; Morris, A.D.; Palmer, C.N.; Kathiresan, S.; Melander, O.; Nilsson, P.M.; Groop, L.C.; Barroso, I.; Langenberg, C.; Wareham, N.J.; O'Callaghan, C.A.; Gloyn, A.L.; Altshuler, D.; Boehnke, M.; Teslovich, T.M.; McCarthy, M.I.; Morris, A.P.; Replication, D.I.A.G.; Meta-analysis, C. url  doi
  Title Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci Type Journal Article
  Year 2015 Publication Nat Genet Abbreviated Journal Nature genetics  
  Volume 47 Issue 12 Pages 1415-1425  
  Keywords HUNT2; metabochip; Binding Sites; Case-Control Studies; Chromatin Immunoprecipitation; *Chromosome Mapping; Diabetes Mellitus, Type 2/*genetics; Gene Expression Regulation; *Genetic Loci; *Genetic Predisposition to Disease; Genome-Wide Association Study; Genomics; Hepatocyte Nuclear Factor 3-beta/*genetics/metabolism; Humans; Islets of Langerhans/metabolism/pathology; Liver/metabolism/pathology; Molecular Sequence Annotation; Polymorphism, Single Nucleotide/*genetics; Receptor, Melatonin, MT2/*genetics/metabolism  
  Abstract We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.Department of Genetics, S Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN ISBN Medium  
  Area Expedition Conference  
  Notes Gaulton, Kyle JFerreira, TeresaLee, YejiRaimondo, AnneMagi, ReedikReschen, Michael EMahajan, AnubhaLocke, AdamWilliam Rayner, NRobertson, NeilScott, Robert AProkopenko, IngaScott, Laura JGreen, ToddSparso, ThomasThuillier, DorotheeYengo, LoicGrallert, HaraldWahl, SimoneFranberg, MattiasStrawbridge, Rona JKestler, HansChheda, HimanshuEisele, LewinGustafsson, StefanSteinthorsdottir, ValgerdurThorleifsson, GudmarQi, LuKarssen, Lennart Cvan Leeuwen, Elisabeth MWillems, Sara MLi, ManChen, HanFuchsberger, ChristianKwan, PhoenixMa, ClementLinderman, MichaelLu, YingchangThomsen, Soren KRundle, Jana KBeer, Nicola Lvan de Bunt, MartijnChalisey, AnilKang, Hyun MinVoight, Benjamin FAbecasis, Goncalo RAlmgren, PeterBaldassarre, DamianoBalkau, BeverleyBenediktsson, RafnBluher, MatthiasBoeing, HeinerBonnycastle, Lori LBottinger, Erwin PBurtt, Noel PCarey, JasonCharpentier, GuillaumeChines, Peter SCornelis, Marilyn CCouper, David JCrenshaw, Andrew Tvan Dam, Rob MDoney, Alex S FDorkhan, MozhganEdkins, SarahEriksson, Johan GEsko, TonuEury, ElodieFadista, JoaoFlannick, JasonFontanillas, PierreFox, CarolineFranks, Paul WGertow, KarlGieger, ChristianGigante, BrunaGottesman, OmriGrant, George BGrarup, NielsGroves, Christopher JHassinen, MaijaHave, Christian THerder, ChristianHolmen, Oddgeir LHreidarsson, Astradur BHumphries, Steve EHunter, David JJackson, Anne UJonsson, AnnaJorgensen, Marit EJorgensen, TorbenKao, Wen-Hong LKerrison, Nicola DKinnunen, LeenaKlopp, NormanKong, AugustineKovacs, PeterKraft, PeterKravic, JasminaLangford, CordeliaLeander, KarinLiang, LimingLichtner, PeterLindgren, Cecilia MLindholm, EeroLinneberg, AllanLiu, Ching-TiLobbens, StephaneLuan, Jian'anLyssenko, ValeriyaMannisto, SatuMcLeod, OlgaMeyer, JuliaMihailov, EvelinMirza, GhazalaMuhleisen, Thomas WMuller-Nurasyid, MartinaNavarro, CarmenNothen, Markus MOskolkov, Nikolay NOwen, Katharine RPalli, DomenicoPechlivanis, SonaliPeltonen, LeenaPerry, John R BPlatou, Carl G PRoden, MichaelRuderfer, DouglasRybin, Denisvan der Schouw, Yvonne TSennblad, BengtSigurethsson, GunnarStancakova, AlenaSteinbach, GeraldStorm, PetterStrauch, KonstantinStringham, Heather MSun, QiThorand, BarbaraTikkanen, EmmiTonjes, AnkeTrakalo, JosephTremoli, ElenaTuomi, TiinamaijaWennauer, RomanWiltshire, StevenWood, Andrew RZeggini, EleftheriaDunham, IanBirney, EwanPasquali, LorenzoFerrer, JorgeLoos, Ruth J FDupuis, JoseeFlorez, Jose CBoerwinkle, EricPankow, James Svan Duijn, CorneliaSijbrands, EricMeigs, James BHu, Frank BThorsteinsdottir, UnnurStefansson, KariLakka, Timo ARauramaa, RainerStumvoll, MichaelPedersen, Nancy LLind, LarsKeinanen-Kiukaanniemi, Sirkka MKorpi-Hyovalti, EevaSaaristo, Timo ESaltevo, JuhaKuusisto, JohannaLaakso, MarkkuMetspalu, AndresErbel, RaimundJocke, Karl-HeinzMoebus, SusanneRipatti, SamuliSalomaa, VeikkoIngelsson, ErikBoehm, Bernhard OBergman, Richard NCollins, Francis SMohlke, Karen LKoistinen, HeikkiTuomilehto, JaakkoHveem, KristianNjolstad, IngerDeloukas, PanagiotisDonnelly, Peter JFrayling, Timothy MHattersley, Andrew Tde Faire, UlfHamsten, AndersIllig, ThomasPeters, AnnetteCauchi, StephaneSladek, RobFroguel, PhilippeHansen, TorbenPedersen, OlufMorris, Andrew DPalmer, Collin N AKathiresan, SekarMelander, OlleNilsson, Peter MGroop, Leif CBarroso, InesLangenberg, ClaudiaWareham, Nicholas JO'Callaghan, Christopher AGloyn, Anna LAltshuler, DavidBoehnke, MichaelTeslovich, Tanya MMcCarthy, Mark IMorris, Andrew P(DIAGRAM)eng098395/Wellcome Trust/United KingdomHHSN268201100005C/HL/NHLBI NIH HHS/HHSN268201100006C/HL/NHLBI NIH HHS/HHSN268201100007C/HL/NHLBI NIH HHS/HHSN268201100008C/HL/NHLBI NIH HHS/HHSN268201100009C/HL/NHLBI NIH HHS/HHSN268201100010C/HL/NHLBI NIH HHS/HHSN268201100011C/HL/NHLBI NIH HHS/HHSN268201100012C/HL/NHLBI NIH HHS/K24 DK080140/DK/NIDDK NIH HHS/N01 HC025195/HC/NHLBI NIH HHS/N01 HG065403/HG/NHGRI NIH HHS/N02 HL64278/HL/NHLBI NIH HHS/R01 AG010175/AG/NIA NIH HHS/R01 DK062370/DK/NIDDK NIH HHS/R01 DK072193/DK/NIDDK NIH HHS/R01 DK073490/DK/NIDDK NIH HHS/R01 DK078616/DK/NIDDK NIH HHS/R01 DK098032/DK/NIDDK NIH HHS/R01 HL059367/HL/NHLBI NIH HHS/R01 HL086694/HL/NHLBI NIH HHS/R01 HL087641/HL/NHLBI NIH HHS/U01 DK085526/DK/NIDDK NIH HHS/U01 DK085545/DK/NIDDK NIH HHS/U01 HG004399/HG/NHGRI NIH HHS/U01 HG004402/HG/NHGRI NIH HHS/UL1 RR025005/RR/NCRR NIH HHS/Z01 HG000024-13/Intramural NIH HHS/2015/11/10 06:00Nat Genet. 2015 Dec;47(12):1415-25. doi: 10.1038/ng.3437. Epub 2015 Nov 9. Approved no  
  Call Number HUNT @ maria.stuifbergen @ Gaulton2015 Serial 1810  
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Author Johnson, M.P.; Brennecke, S.P.; East, C.E.; Goring, H.H.H.; Kent, J.W.J.; Dyer, T.D.; Said, J.M.; Roten, L.T.; Iversen, A.-C.; Abraham, L.J.; Heinonen, S.; Kajantie, E.; Kere, J.; Kivinen, K.; Pouta, A.; Laivuori, H.; Austgulen, R.; Blangero, J.; Moses, E.K. url  doi
  Title Genome-wide association scan identifies a risk locus for preeclampsia on 2q14, near the inhibin, beta B gene Type Journal Article
  Year 2012 Publication PloS one Abbreviated Journal PLoS One  
  Volume 7 Issue 3 Pages e33666  
  Keywords Australia; Chromosomes, Human, Pair 2/*genetics; Cohort Studies; Computational Biology; Female; Finland; Gene Expression Regulation; Genetic Loci/*genetics; *Genetic Predisposition to Disease; Genome, Human/genetics; *Genome-Wide Association Study; Humans; Inhibin-beta Subunits/*genetics/metabolism; Norway; Polymorphism, Single Nucleotide/genetics; Pre-Eclampsia/*genetics; Pregnancy; Reproducibility of Results; Risk Factors; Sequence Analysis, DNA  
  Abstract Elucidating the genetic architecture of preeclampsia is a major goal in obstetric medicine. We have performed a genome-wide association study (GWAS) for preeclampsia in unrelated Australian individuals of Caucasian ancestry using the Illumina OmniExpress-12 BeadChip to successfully genotype 648,175 SNPs in 538 preeclampsia cases and 540 normal pregnancy controls. Two SNP associations (rs7579169, p = 3.58x10(-7), OR = 1.57; rs12711941, p = 4.26x10(-7), OR = 1.56) satisfied our genome-wide significance threshold (modified Bonferroni p<5.11x10(-7)). These SNPs reside in an intergenic region less than 15 kb downstream from the 3' terminus of the Inhibin, beta B (INHBB) gene on 2q14.2. They are in linkage disequilibrium (LD) with each other (r(2) = 0.92), but not (r(2)<0.80) with any other genotyped SNP +/-250 kb. DNA re-sequencing in and around the INHBB structural gene identified an additional 25 variants. Of the 21 variants that we successfully genotyped back in the case-control cohort the most significant association observed was for a third intergenic SNP (rs7576192, p = 1.48x10(-7), OR = 1.59) in strong LD with the two significant GWAS SNPs (r(2)>0.92). We attempted to provide evidence of a putative regulatory role for these SNPs using bioinformatic analyses and found that they all reside within regions of low sequence conservation and/or low complexity, suggesting functional importance is low. We also explored the mRNA expression in decidua of genes +/-500 kb of INHBB and found a nominally significant correlation between a transcript encoded by the EPB41L5 gene, approximately 250 kb centromeric to INHBB, and preeclampsia (p = 0.03). We were unable to replicate the associations shown by the significant GWAS SNPs in case-control cohorts from Norway and Finland, leading us to conclude that it is more likely that these SNPs are in LD with as yet unidentified causal variant(s).  
  Address Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, United States of America  
  Corporate Author FINNPEC Study Group Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:22432041; PMC3303857 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1534  
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