toggle visibility Search & Display Options

Select All    Deselect All
 |   | 
Details
   print
  Records Links
Author (up) 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  
Permanent link to this record
 

 
Author (up) Gusarova, V.; O'Dushlaine, C.; Teslovich, T.M.; Benotti, P.N.; Mirshahi, T.; Gottesman, O.; Van Hout, C.V.; Murray, M.F.; Mahajan, A.; Nielsen, J.B.; Fritsche, L.; Wulff, A.B.; Gudbjartsson, D.F.; Sjogren, M.; Emdin, C.A.; Scott, R.A.; Lee, W.-J.; Small, A.; Kwee, L.C.; Dwivedi, O.P.; Prasad, R.B.; Bruse, S.; Lopez, A.E.; Penn, J.; Marcketta, A.; Leader, J.B.; Still, C.D.; Kirchner, H.L.; Mirshahi, U.L.; Wardeh, A.H.; Hartle, C.M.; Habegger, L.; Fetterolf, S.N.; Tusie-Luna, T.; Morris, A.P.; Holm, H.; Steinthorsdottir, V.; Sulem, P.; Thorsteinsdottir, U.; Rotter, J.I.; Chuang, L.-M.; Damrauer, S.; Birtwell, D.; Brummett, C.M.; Khera, A.V.; Natarajan, P.; Orho-Melander, M.; Flannick, J.; Lotta, L.A.; Willer, C.J.; Holmen, O.L.; Ritchie, M.D.; Ledbetter, D.H.; Murphy, A.J.; Borecki, I.B.; Reid, J.G.; Overton, J.D.; Hansson, O.; Groop, L.; Shah, S.H.; Kraus, W.E.; Rader, D.J.; Chen, Y.-D.I.; Hveem, K.; Wareham, N.J.; Kathiresan, S.; Melander, O.; Stefansson, K.; Nordestgaard, B.G.; Tybjaerg-Hansen, A.; Abecasis, G.R.; Altshuler, D.; Florez, J.C.; Boehnke, M.; McCarthy, M.I.; Yancopoulos, G.D.; Carey, D.J.; Shuldiner, A.R.; Baras, A.; Dewey, F.E.; Gromada, J. url  doi
  Title Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes Type Journal Article
  Year 2018 Publication Nature Communications Abbreviated Journal Nat Commun  
  Volume 9 Issue 1 Pages 2252  
  Keywords Amino Acid Substitution; Angiopoietin-like 4 Protein/*deficiency/*genetics/metabolism; Animals; Blood Glucose/metabolism; Case-Control Studies; Diabetes Mellitus, Type 2/etiology/*genetics/*metabolism; Female; Gene Silencing; Genetic Association Studies; Genetic Variation; Heterozygote; Homeostasis; Humans; Insulin Resistance/genetics; Lipoprotein Lipase/metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Risk Factors; Whole Exome Sequencing  
  Abstract Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 x 10(-10)), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.  
  Address Regeneron Pharmaceuticals, Tarrytown, 10591, NY, USA. jesper.gromada@regeneron.com  
  Corporate Author 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 2041-1723 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:29899519; PMCID:PMC5997992 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 2086  
Permanent link to this record
 

 
Author (up) Lange, L.A.; Hu, Y.; Zhang, H.; Xue, C.; Schmidt, E.M.; Tang, Z.-Z.; Bizon, C.; Lange, E.M.; Smith, J.D.; Turner, E.H.; Jun, G.; Kang, H.M.; Peloso, G.; Auer, P.; Li, K.-P.; Flannick, J.; Zhang, J.; Fuchsberger, C.; Gaulton, K.; Lindgren, C.; Locke, A.; Manning, A.; Sim, X.; Rivas, M.A.; Holmen, O.L.; Gottesman, O.; Lu, Y.; Ruderfer, D.; Stahl, E.A.; Duan, Q.; Li, Y.; Durda, P.; Jiao, S.; Isaacs, A.; Hofman, A.; Bis, J.C.; Correa, A.; Griswold, M.E.; Jakobsdottir, J.; Smith, A.V.; Schreiner, P.J.; Feitosa, M.F.; Zhang, Q.; Huffman, J.E.; Crosby, J.; Wassel, C.L.; Do, R.; Franceschini, N.; Martin, L.W.; Robinson, J.G.; Assimes, T.L.; Crosslin, D.R.; Rosenthal, E.A.; Tsai, M.; Rieder, M.J.; Farlow, D.N.; Folsom, A.R.; Lumley, T.; Fox, E.R.; Carlson, C.S.; Peters, U.; Jackson, R.D.; van Duijn, C.M.; Uitterlinden, A.G.; Levy, D.; Rotter, J.I.; Taylor, H.A.; Gudnason, V.J.; Siscovick, D.S.; Fornage, M.; Borecki, I.B.; Hayward, C.; Rudan, I.; Chen, Y.E.; Bottinger, E.P.; Loos, R.J.F.; Saetrom, P.; Hveem, K.; Boehnke, M.; Groop, L.; McCarthy, M.; Meitinger, T.; Ballantyne, C.M.; Gabriel, S.B.; O'Donnell, C.J.; Post, W.S.; North, K.E.; Reiner, A.P.; Boerwinkle, E.; Psaty, B.M.; Altshuler, D.; Kathiresan, S.; Lin, D.-Y.; Jarvik, G.P.; Cupples, L.A.; Kooperberg, C.; Wilson, J.G.; Nickerson, D.A.; Abecasis, G.R.; Rich, S.S.; Tracy, R.P.; Willer, C.J. url  doi
  Title Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol Type Journal Article
  Year 2014 Publication American Journal of Human Genetics Abbreviated Journal Am J Hum Genet  
  Volume 94 Issue 2 Pages 233-245  
  Keywords Adult; Aged; Apolipoproteins E/blood/genetics; Cholesterol, LDL/*genetics; Cohort Studies; Dyslipidemias/blood/genetics; *Exome; Female; Follow-Up Studies; *Gene Frequency; Genetic Code; *Genome-Wide Association Study; Genotype; Humans; Lipase/genetics; Male; Middle Aged; Phenotype; *Polymorphism, Single Nucleotide; Proprotein Convertases/genetics; Receptors, LDL/genetics; Sequence Analysis, DNA; Serine Endopeptidases/genetics; HUNT3  
  Abstract Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.  
  Address Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: cristen@umich.edu  
  Corporate Author NHLBI Grand Opportunity Exome Sequencing Project 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 0002-9297 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:24507775; PMC3928660 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1625  
Permanent link to this record
Select All    Deselect All
 |   | 
Details
   print

Save Citations:
Export Records: