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Author (up) Holmen, O.L.; Zhang, H.; Fan, Y.; Hovelson, D.H.; Schmidt, E.M.; Zhou, W.; Guo, Y.; Zhang, J.; Langhammer, A.; Lochen, M.-L.; Ganesh, S.K.; Vatten, L.; Skorpen, F.; Dalen, H.; Zhang, J.; Pennathur, S.; Chen, J.; Platou, C.; Mathiesen, E.B.; Wilsgaard, T.; Njolstad, I.; Boehnke, M.; Chen, Y.E.; Abecasis, G.R.; Hveem, K.; Willer, C.J. url  doi
  Title Systematic evaluation of coding variation identifies a candidate causal variant in TM6SF2 influencing total cholesterol and myocardial infarction risk Type Journal Article
  Year 2014 Publication Nature Genetics Abbreviated Journal Nat Genet  
  Volume 46 Issue 4 Pages 345-351  
  Keywords Animals; Cholesterol, LDL/blood/genetics; Exome/genetics; Gene Knockdown Techniques; *Genetic Variation; Genome-Wide Association Study; Genotype; Humans; Lipids/*blood/genetics; Membrane Proteins/*genetics; Mice; Mice, Inbred C57BL; Mutation, Missense/genetics; Myocardial Infarction/*epidemiology/*genetics; Norway/epidemiology; Risk Factors  
  Abstract Blood lipid levels are heritable, treatable risk factors for cardiovascular disease. We systematically assessed genome-wide coding variation to identify new genes influencing lipid traits, fine map known lipid loci and evaluate whether low-frequency variants with large effects exist for these traits. Using an exome array, we genotyped 80,137 coding variants in 5,643 Norwegians. We followed up 18 variants in 4,666 Norwegians and identified ten loci with coding variants associated with a lipid trait (P < 5 x 10(-8)). One variant in TM6SF2 (encoding p.Glu167Lys), residing in a known genome-wide association study locus for lipid traits, influences total cholesterol levels and is associated with myocardial infarction. Transient TM6SF2 overexpression or knockdown of Tm6sf2 in mice alters serum lipid profiles, consistent with the association observed in humans, identifying TM6SF2 as a functional gene within a locus previously known as NCAN-CILP2-PBX4 or 19p13. This study demonstrates that systematic assessment of coding variation can quickly point to a candidate causal gene.  
  Address 1] Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA. [3] Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA  
  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 1061-4036 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:24633158 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1597  
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
 

 
Author (up) Liu, D.J.; Peloso, G.M.; Yu, H.; Butterworth, A.S.; Wang, X.; Mahajan, A.; Saleheen, D.; Emdin, C.; Alam, D.; Alves, A.C.; Amouyel, P.; Di Angelantonio, E.; Arveiler, D.; Assimes, T.L.; Auer, P.L.; Baber, U.; Ballantyne, C.M.; Bang, L.E.; Benn, M.; Bis, J.C.; Boehnke, M.; Boerwinkle, E.; Bork-Jensen, J.; Bottinger, E.P.; Brandslund, I.; Brown, M.; Busonero, F.; Caulfield, M.J.; Chambers, J.C.; Chasman, D.I.; Chen, Y.E.; Chen, Y.-D.I.; Chowdhury, R.; Christensen, C.; Chu, A.Y.; Connell, J.M.; Cucca, F.; Cupples, L.A.; Damrauer, S.M.; Davies, G.; Deary, I.J.; Dedoussis, G.; Denny, J.C.; Dominiczak, A.; Dube, M.-P.; Ebeling, T.; Eiriksdottir, G.; Esko, T.; Farmaki, A.-E.; Feitosa, M.F.; Ferrario, M.; Ferrieres, J.; Ford, I.; Fornage, M.; Franks, P.W.; Frayling, T.M.; Frikke-Schmidt, R.; Fritsche, L.G.; Frossard, P.; Fuster, V.; Ganesh, S.K.; Gao, W.; Garcia, M.E.; Gieger, C.; Giulianini, F.; Goodarzi, M.O.; Grallert, H.; Grarup, N.; Groop, L.; Grove, M.L.; Gudnason, V.; Hansen, T.; Harris, T.B.; Hayward, C.; Hirschhorn, J.N.; Holmen, O.L.; Huffman, J.; Huo, Y.; Hveem, K.; Jabeen, S.; Jackson, A.U.; Jakobsdottir, J.; Jarvelin, M.-R.; Jensen, G.B.; Jorgensen, M.E.; Jukema, J.W.; Justesen, J.M.; Kamstrup, P.R.; Kanoni, S.; Karpe, F.; Kee, F.; Khera, A.V.; Klarin, D.; Koistinen, H.A.; Kooner, J.S.; Kooperberg, C.; Kuulasmaa, K.; Kuusisto, J.; Laakso, M.; Lakka, T.; Langenberg, C.; Langsted, A.; Launer, L.J.; Lauritzen, T.; Liewald, D.C.M.; Lin, L.A.; Linneberg, A.; Loos, R.J.F.; Lu, Y.; Lu, X.; Magi, R.; Malarstig, A.; Manichaikul, A.; Manning, A.K.; Mantyselka, P.; Marouli, E.; Masca, N.G.D.; Maschio, A.; Meigs, J.B.; Melander, O.; Metspalu, A.; Morris, A.P.; Morrison, A.C.; Mulas, A.; Muller-Nurasyid, M.; Munroe, P.B.; Neville, M.J.; Nielsen, J.B.; Nielsen, S.F.; Nordestgaard, B.G.; Ordovas, J.M.; Mehran, R.; O'Donnell, C.J.; Orho-Melander, M.; Molony, C.M.; Muntendam, P.; Padmanabhan, S.; Palmer, C.N.A.; Pasko, D.; Patel, A.P.; Pedersen, O.; Perola, M.; Peters, A.; Pisinger, C.; Pistis, G.; Polasek, O.; Poulter, N.; Psaty, B.M.; Rader, D.J.; Rasheed, A.; Rauramaa, R.; Reilly, D.F.; Reiner, A.P.; Renstrom, F.; Rich, S.S.; Ridker, P.M.; Rioux, J.D.; Robertson, N.R.; Roden, D.M.; Rotter, J.I.; Rudan, I.; Salomaa, V.; Samani, N.J.; Sanna, S.; Sattar, N.; Schmidt, E.M.; Scott, R.A.; Sever, P.; Sevilla, R.S.; Shaffer, C.M.; Sim, X.; Sivapalaratnam, S.; Small, K.S.; Smith, A.V.; Smith, B.H.; Somayajula, S.; Southam, L.; Spector, T.D.; Speliotes, E.K.; Starr, J.M.; Stirrups, K.E.; Stitziel, N.; Strauch, K.; Stringham, H.M.; Surendran, P.; Tada, H.; Tall, A.R.; Tang, H.; Tardif, J.-C.; Taylor, K.D.; Trompet, S.; Tsao, P.S.; Tuomilehto, J.; Tybjaerg-Hansen, A.; van Zuydam, N.R.; Varbo, A.; Varga, T.V.; Virtamo, J.; Waldenberger, M.; Wang, N.; Wareham, N.J.; Warren, H.R.; Weeke, P.E.; Weinstock, J.; Wessel, J.; Wilson, J.G.; Wilson, P.W.F.; Xu, M.; Yaghootkar, H.; Young, R.; Zeggini, E.; Zhang, H.; Zheng, N.S.; Zhang, W.; Zhang, Y.; Zhou, W.; Zhou, Y.; Zoledziewska, M.; Howson, J.M.M.; Danesh, J.; McCarthy, M.I.; Cowan, C.A.; Abecasis, G.; Deloukas, P.; Musunuru, K.; Willer, C.J.; Kathiresan, S. url  doi
  Title Exome-wide association study of plasma lipids in >300,000 individuals Type Journal Article
  Year 2017 Publication Nature Genetics Abbreviated Journal Nat Genet  
  Volume 49 Issue 12 Pages 1758-1766  
  Keywords Coronary Artery Disease/blood/genetics; Diabetes Mellitus, Type 2/blood/genetics; Exome/*genetics; Genetic Association Studies/*methods; Genetic Predisposition to Disease/genetics; *Genetic Variation; Genotype; Humans; Lipids/*blood; Macular Degeneration/blood/genetics; Phenotype; Risk Factors  
  Abstract We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.  
  Address Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA  
  Corporate Author VA Million Veteran Program 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 1061-4036 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:29083408; PMCID:PMC5709146 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1943  
Permanent link to this record
 

 
Author (up) Locke, A.E.; Kahali, B.; Berndt, S.I.; Justice, A.E.; Pers, T.H.; Day, F.R.; Powell, C.; Vedantam, S.; Buchkovich, M.L.; Yang, J.; Croteau-Chonka, D.C.; Esko, T.; Fall, T.; Ferreira, T.; Gustafsson, S.; Kutalik, Z.; Luan, J.'an; Magi, R.; Randall, J.C.; Winkler, T.W.; Wood, A.R.; Workalemahu, T.; Faul, J.D.; Smith, J.A.; Hua Zhao, J.; Zhao, W.; Chen, J.; Fehrmann, R.; Hedman, A.K.; Karjalainen, J.; Schmidt, E.M.; Absher, D.; Amin, N.; Anderson, D.; Beekman, M.; Bolton, J.L.; Bragg-Gresham, J.L.; Buyske, S.; Demirkan, A.; Deng, G.; Ehret, G.B.; Feenstra, B.; Feitosa, M.F.; Fischer, K.; Goel, A.; Gong, J.; Jackson, A.U.; Kanoni, S.; Kleber, M.E.; Kristiansson, K.; Lim, U.; Lotay, V.; Mangino, M.; Mateo Leach, I.; Medina-Gomez, C.; Medland, S.E.; Nalls, M.A.; Palmer, C.D.; Pasko, D.; Pechlivanis, S.; Peters, M.J.; Prokopenko, I.; Shungin, D.; Stancakova, A.; Strawbridge, R.J.; Ju Sung, Y.; Tanaka, T.; Teumer, A.; Trompet, S.; van der Laan, S.W.; van Setten, J.; Van Vliet-Ostaptchouk, J.V.; Wang, Z.; Yengo, L.; Zhang, W.; Isaacs, A.; Albrecht, E.; Arnlov, J.; Arscott, G.M.; Attwood, A.P.; Bandinelli, S.; Barrett, A.; Bas, I.N.; Bellis, C.; Bennett, A.J.; Berne, C.; Blagieva, R.; Bluher, M.; Bohringer, S.; Bonnycastle, L.L.; Bottcher, Y.; Boyd, H.A.; Bruinenberg, M.; Caspersen, I.H.; Ida Chen, Y.-D.; Clarke, R.; Warwick Daw, E.; de Craen, A.J.M.; Delgado, G.; Dimitriou, M.; Doney, A.S.F.; Eklund, N.; Estrada, K.; Eury, E.; Folkersen, L.; Fraser, R.M.; Garcia, M.E.; Geller, F.; Giedraitis, V.; Gigante, B.; Go, A.S.; Golay, A.; Goodall, A.H.; Gordon, S.D.; Gorski, M.; Grabe, H.-J.; Grallert, H.; Grammer, T.B.; Grassler, J.; Gronberg, H.; Groves, C.J.; Gusto, G.; Haessler, J.; Hall, P.; Haller, T.; Hallmans, G.; Hartman, C.A.; Hassinen, M.; Hayward, C.; Heard-Costa, N.L.; Helmer, Q.; Hengstenberg, C.; Holmen, O.; Hottenga, J.-J.; James, A.L.; Jeff, J.M.; Johansson, A.; Jolley, J.; Juliusdottir, T.; Kinnunen, L.; Koenig, W.; Koskenvuo, M.; Kratzer, W.; Laitinen, J.; Lamina, C.; Leander, K.; Lee, N.R.; Lichtner, P.; Lind, L.; Lindstrom, J.; Sin Lo, K.; Lobbens, S.; Lorbeer, R.; Lu, Y.; Mach, F.; Magnusson, P.K.E.; Mahajan, A.; McArdle, W.L.; McLachlan, S.; Menni, C.; Merger, S.; Mihailov, E.; Milani, L.; Moayyeri, A.; Monda, K.L.; Morken, M.A.; Mulas, A.; Muller, G.; Muller-Nurasyid, M.; Musk, A.W.; Nagaraja, R.; Nothen, M.M.; Nolte, I.M.; Pilz, S.; Rayner, N.W.; Renstrom, F.; Rettig, R.; Ried, J.S.; Ripke, S.; Robertson, N.R.; Rose, L.M.; Sanna, S.; Scharnagl, H.; Scholtens, S.; Schumacher, F.R.; Scott, W.R.; Seufferlein, T.; Shi, J.; Vernon Smith, A.; Smolonska, J.; Stanton, A.V.; Steinthorsdottir, V.; Stirrups, K.; Stringham, H.M.; Sundstrom, J.; Swertz, M.A.; Swift, A.J.; Syvanen, A.-C.; Tan, S.-T.; Tayo, B.O.; Thorand, B.; Thorleifsson, G.; Tyrer, J.P.; Uh, H.-W.; Vandenput, L.; Verhulst, F.C.; Vermeulen, S.H.; Verweij, N.; Vonk, J.M.; Waite, L.L.; Warren, H.R.; Waterworth, D.; Weedon, M.N.; Wilkens, L.R.; Willenborg, C.; Wilsgaard, T.; Wojczynski, M.K.; Wong, A.; Wright, A.F.; Zhang, Q.; Brennan, E.P.; Choi, M.; Dastani, Z.; Drong, A.W.; Eriksson, P.; Franco-Cereceda, A.; Gadin, J.R.; Gharavi, A.G.; Goddard, M.E.; Handsaker, R.E.; Huang, J.; Karpe, F.; Kathiresan, S.; Keildson, S.; Kiryluk, K.; Kubo, M.; Lee, J.-Y.; Liang, L.; Lifton, R.P.; Ma, B.; McCarroll, S.A.; McKnight, A.J.; Min, J.L.; Moffatt, M.F.; Montgomery, G.W.; Murabito, J.M.; Nicholson, G.; Nyholt, D.R.; Okada, Y.; Perry, J.R.B.; Dorajoo, R.; Reinmaa, E.; Salem, R.M.; Sandholm, N.; Scott, R.A.; Stolk, L.; Takahashi, A.; Tanaka, T.; Van't Hooft, F.M.; Vinkhuyzen, A.A.E.; Westra, H.-J.; Zheng, W.; Zondervan, K.T.; Heath, A.C.; Arveiler, D.; Bakker, S.J.L.; Beilby, J.; Bergman, R.N.; Blangero, J.; Bovet, P.; Campbell, H.; Caulfield, M.J.; Cesana, G.; Chakravarti, A.; Chasman, D.I.; Chines, P.S.; Collins, F.S.; Crawford, D.C.; Adrienne Cupples, L.; Cusi, D.; Danesh, J.; de Faire, U.; den Ruijter, H.M.; Dominiczak, A.F.; Erbel, R.; Erdmann, J.; Eriksson, J.G.; Farrall, M.; Felix, S.B.; Ferrannini, E.; Ferrieres, J.; Ford, I.; Forouhi, N.G.; Forrester, T.; Franco, O.H.; Gansevoort, R.T.; Gejman, P.V.; Gieger, C.; Gottesman, O.; Gudnason, V.; Gyllensten, U.; Hall, A.S.; Harris, T.B.; Hattersley, A.T.; Hicks, A.A.; Hindorff, L.A.; Hingorani, A.D.; Hofman, A.; Homuth, G.; Kees Hovingh, G.; Humphries, S.E.; Hunt, S.C.; Hypponen, E.; Illig, T.; Jacobs, K.B.; Jarvelin, M.-R.; Jockel, K.-H.; Johansen, B.; Jousilahti, P.; Wouter Jukema, J.; Jula, A.M.; Kaprio, J.; Kastelein, J.J.P.; Keinanen-Kiukaanniemi, S.M.; Kiemeney, L.A.; Knekt, P.; Kooner, J.S.; Kooperberg, C.; Kovacs, P.; Kraja, A.T.; Kumari, M.; Kuusisto, J.; Lakka, T.A.; Langenberg, C.; Le Marchand, L.; Lehtimaki, T.; Lyssenko, V.; Mannisto, S.; Marette, A.; Matise, T.C.; McKenzie, C.A.; McKnight, B.; Moll, F.L.; Morris, A.D.; Morris, A.P.; Murray, J.C.; Nelis, M.; Ohlsson, C.; Oldehinkel, A.J.; Ong, K.K.; Madden, P.A.F.; Pasterkamp, G.; Peden, J.F.; Peters, A.; Postma, D.S.; Pramstaller, P.P.; Price, J.F.; Qi, L.; Raitakari, O.T.; Rankinen, T.; Rao, D.C.; Rice, T.K.; Ridker, P.M.; Rioux, J.D.; Ritchie, M.D.; Rudan, I.; Salomaa, V.; Samani, N.J.; Saramies, J.; Sarzynski, M.A.; Schunkert, H.; Schwarz, P.E.H.; Sever, P.; Shuldiner, A.R.; Sinisalo, J.; Stolk, R.P.; Strauch, K.; Tonjes, A.; Tregouet, D.-A.; Tremblay, A.; Tremoli, E.; Virtamo, J.; Vohl, M.-C.; Volker, U.; Waeber, G.; Willemsen, G.; Witteman, J.C.; Zillikens, M.C.; Adair, L.S.; Amouyel, P.; Asselbergs, F.W.; Assimes, T.L.; Bochud, M.; Boehm, B.O.; Boerwinkle, E.; Bornstein, S.R.; Bottinger, E.P.; Bouchard, C.; Cauchi, S.; Chambers, J.C.; Chanock, S.J.; Cooper, R.S.; de Bakker, P.I.W.; Dedoussis, G.; Ferrucci, L.; Franks, P.W.; Froguel, P.; Groop, L.C.; Haiman, C.A.; Hamsten, A.; Hui, J.; Hunter, D.J.; Hveem, K.; Kaplan, R.C.; Kivimaki, M.; Kuh, D.; Laakso, M.; Liu, Y.; Martin, N.G.; Marz, W.; Melbye, M.; Metspalu, A.; Moebus, S.; Munroe, P.B.; Njolstad, I.; Oostra, B.A.; Palmer, C.N.A.; Pedersen, N.L.; Perola, M.; Perusse, L.; Peters, U.; Power, C.; Quertermous, T.; Rauramaa, R.; Rivadeneira, F.; Saaristo, T.E.; Saleheen, D.; Sattar, N.; Schadt, E.E.; Schlessinger, D.; Eline Slagboom, P.; Snieder, H.; Spector, T.D.; Thorsteinsdottir, U.; Stumvoll, M.; Tuomilehto, J.; Uitterlinden, A.G.; Uusitupa, M.; van der Harst, P.; Walker, M.; Wallaschofski, H.; Wareham, N.J.; Watkins, H.; Weir, D.R.; Wichmann, H.-E.; Wilson, J.F.; Zanen, P.; Borecki, I.B.; Deloukas, P.; Fox, C.S.; Heid, I.M.; O'Connell, J.R.; Strachan, D.P.; Stefansson, K.; van Duijn, C.M.; Abecasis, G.R.; Franke, L.; Frayling, T.M.; McCarthy, M.I.; Visscher, P.M.; Scherag, A.; Willer, C.J.; Boehnke, M.; Mohlke, K.L.; Lindgren, C.M.; Beckmann, J.S.; Barroso, I.; North, K.E.; Ingelsson, E.; Hirschhorn, J.N.; Loos, R.J.F.; Speliotes, E.K. url  doi
  Title Genetic studies of body mass index yield new insights for obesity biology Type Journal Article
  Year 2015 Publication Nature Abbreviated Journal Nature  
  Volume 518 Issue 7538 Pages 197-206  
  Keywords HUNT3; obesity; genetics  
  Abstract Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for approximately 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.  
  Address Department of Internal Medicine, Division of Gastroenterology, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA  
  Corporate Author International Endogene Consortium 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 0028-0836 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:25673413 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1673  
Permanent link to this record
 

 
Author (up) Nielsen, J.B.; Fritsche, L.G.; Zhou, W.; Teslovich, T.M.; Holmen, O.L.; Gustafsson, S.; Gabrielsen, M.E.; Schmidt, E.M.; Beaumont, R.; Wolford, B.N.; Lin, M.; Brummett, C.M.; Preuss, M.H.; Refsgaard, L.; Bottinger, E.P.; Graham, S.E.; Surakka, I.; Chu, Y.; Skogholt, A.H.; Dalen, H.; Boyle, A.P.; Oral, H.; Herron, T.J.; Kitzman, J.; Jalife, J.; Svendsen, J.H.; Olesen, M.S.; Njolstad, I.; Lochen, M.-L.; Baras, A.; Gottesman, O.; Marcketta, A.; O'Dushlaine, C.; Ritchie, M.D.; Wilsgaard, T.; Loos, R.J.F.; Frayling, T.M.; Boehnke, M.; Ingelsson, E.; Carey, D.J.; Dewey, F.E.; Kang, H.M.; Abecasis, G.R.; Hveem, K.; Willer, C.J. url  doi
  Title Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development Type Journal Article
  Year 2018 Publication American Journal of Human Genetics Abbreviated Journal Am J Hum Genet  
  Volume 102 Issue 1 Pages 103-115  
  Keywords Atrial Fibrillation/*genetics; *Genetic Loci; *Genetic Predisposition to Disease; *Genome-Wide Association Study; Heart/*embryology; Humans; Inheritance Patterns/genetics; Multifactorial Inheritance/genetics; Organ Specificity/genetics; Physical Chromosome Mapping; Quantitative Trait Loci/genetics; Regulatory Sequences, Nucleic Acid/*genetics; Reproducibility of Results; Risk Factors; *Cdkn2c; *Dmrta2; *Gwas; *Ttn; *atrial fibrillation; *cardiomyopathy; *fetal; *genetic risk score; *heart; *pathway  
  Abstract Atrial fibrillation (AF) is a common cardiac arrhythmia and a major risk factor for stroke, heart failure, and premature death. The pathogenesis of AF remains poorly understood, which contributes to the current lack of highly effective treatments. To understand the genetic variation and biology underlying AF, we undertook a genome-wide association study (GWAS) of 6,337 AF individuals and 61,607 AF-free individuals from Norway, including replication in an additional 30,679 AF individuals and 278,895 AF-free individuals. Through genotyping and dense imputation mapping from whole-genome sequencing, we tested almost nine million genetic variants across the genome and identified seven risk loci, including two novel loci. One novel locus (lead single-nucleotide variant [SNV] rs12614435; p = 6.76 x 10(-18)) comprised intronic and several highly correlated missense variants situated in the I-, A-, and M-bands of titin, which is the largest protein in humans and responsible for the passive elasticity of heart and skeletal muscle. The other novel locus (lead SNV rs56202902; p = 1.54 x 10(-11)) covered a large, gene-dense chromosome 1 region that has previously been linked to cardiac conduction. Pathway and functional enrichment analyses suggested that many AF-associated genetic variants act through a mechanism of impaired muscle cell differentiation and tissue formation during fetal heart development.  
  Address Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA; Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim 7491, Norway; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: cristen@umich.edu  
  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 0002-9297 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:29290336; PMCID:PMC5777936 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 2143  
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Author (up) Nielsen, J.B.; Thorolfsdottir, R.B.; Fritsche, L.G.; Zhou, W.; Skov, M.W.; Graham, S.E.; Herron, T.J.; McCarthy, S.; Schmidt, E.M.; Sveinbjornsson, G.; Surakka, I.; Mathis, M.R.; Yamazaki, M.; Crawford, R.D.; Gabrielsen, M.E.; Skogholt, A.H.; Holmen, O.L.; Lin, M.; Wolford, B.N.; Dey, R.; Dalen, H.; Sulem, P.; Chung, J.H.; Backman, J.D.; Arnar, D.O.; Thorsteinsdottir, U.; Baras, A.; O'Dushlaine, C.; Holst, A.G.; Wen, X.; Hornsby, W.; Dewey, F.E.; Boehnke, M.; Kheterpal, S.; Mukherjee, B.; Lee, S.; Kang, H.M.; Holm, H.; Kitzman, J.; Shavit, J.A.; Jalife, J.; Brummett, C.M.; Teslovich, T.M.; Carey, D.J.; Gudbjartsson, D.F.; Stefansson, K.; Abecasis, G.R.; Hveem, K.; Willer, C.J. url  doi
  Title Biobank-driven genomic discovery yields new insight into atrial fibrillation biology Type Journal Article
  Year 2018 Publication Nature Genetics Abbreviated Journal Nat Genet  
  Volume 50 Issue 9 Pages 1234-1239  
  Keywords  
  Abstract To identify genetic variation underlying atrial fibrillation, the most common cardiac arrhythmia, we performed a genome-wide association study of >1,000,000 people, including 60,620 atrial fibrillation cases and 970,216 controls. We identified 142 independent risk variants at 111 loci and prioritized 151 functional candidate genes likely to be involved in atrial fibrillation. Many of the identified risk variants fall near genes where more deleterious mutations have been reported to cause serious heart defects in humans (GATA4, MYH6, NKX2-5, PITX2, TBX5)(1), or near genes important for striated muscle function and integrity (for example, CFL2, MYH7, PKP2, RBM20, SGCG, SSPN). Pathway and functional enrichment analyses also suggested that many of the putative atrial fibrillation genes act via cardiac structural remodeling, potentially in the form of an 'atrial cardiomyopathy'(2), either during fetal heart development or as a response to stress in the adult heart.  
  Address Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA. cristen@umich.edu  
  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 1061-4036 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:30061737 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 2144  
Permanent link to this record
 

 
Author (up) Shungin, D.; Winkler, T.W.; Croteau-Chonka, D.C.; Ferreira, T.; Locke, A.E.; Magi, R.; Strawbridge, R.J.; Pers, T.H.; Fischer, K.; Justice, A.E.; Workalemahu, T.; Wu, J.M.; Buchkovich, M.L.; Heard-Costa, N.L.; Roman, T.S.; Drong, A.W.; Song, C.; Gustafsson, S.; Day, F.R.; Esko, T.; Fall, T.; Kutalik, Z.; Luan, J.; Randall, J.C.; Scherag, A.; Vedantam, S.; Wood, A.R.; Chen, J.; Fehrmann, R.; Karjalainen, J.; Kahali, B.; Liu, C.T.; Schmidt, E.M.; Absher, D.; Amin, N.; Anderson, D.; Beekman, M.; Bragg-Gresham, J.L.; Buyske, S.; Demirkan, A.; Ehret, G.B.; Feitosa, M.F.; Goel, A.; Jackson, A.U.; Johnson, T.; Kleber, M.E.; Kristiansson, K.; Mangino, M.; Mateo Leach, I.; Medina-Gomez, C.; Palmer, C.D.; Pasko, D.; Pechlivanis, S.; Peters, M.J.; Prokopenko, I.; Stancakova, A.; Ju Sung, Y.; Tanaka, T.; Teumer, A.; Van Vliet-Ostaptchouk, J.V.; Yengo, L.; Zhang, W.; Albrecht, E.; Arnlov, J.; Arscott, G.M.; Bandinelli, S.; Barrett, A.; Bellis, C.; Bennett, A.J.; Berne, C.; Bluher, M.; Bohringer, S.; Bonnet, F.; Bottcher, Y.; Bruinenberg, M.; Carba, D.B.; Caspersen, I.H.; Clarke, R.; Daw, E.W.; Deelen, J.; Deelman, E.; Delgado, G.; Doney, A.S.; Eklund, N.; Erdos, M.R.; Estrada, K.; Eury, E.; Friedrich, N.; Garcia, M.E.; Giedraitis, V.; Gigante, B.; Go, A.S.; Golay, A.; Grallert, H.; Grammer, T.B.; Grassler, J.; Grewal, J.; Groves, C.J.; Haller, T.; Hallmans, G.; Hartman, C.A.; Hassinen, M.; Hayward, C.; Heikkila, K.; Herzig, K.H.; Helmer, Q.; Hillege, H.L.; Holmen, O.; Hunt, S.C.; Isaacs, A.; Ittermann, T.; James, A.L.; Johansson, I.; Juliusdottir, T.; Kalafati, I.P.; Kinnunen, L.; Koenig, W.; Kooner, I.K.; Kratzer, W.; Lamina, C.; Leander, K.; Lee, N.R.; Lichtner, P.; Lind, L.; Lindstrom, J.; Lobbens, S.; Lorentzon, M.; Mach, F.; Magnusson, P.K.; Mahajan, A.; McArdle, W.L.; Menni, C.; Merger, S.; Mihailov, E.; Milani, L.; Mills, R.; Moayyeri, A.; Monda, K.L.; Mooijaart, S.P.; Muhleisen, T.W.; Mulas, A.; Muller, G.; Muller-Nurasyid, M.; Nagaraja, R.; Nalls, M.A.; Narisu, N.; Glorioso, N.; Nolte, I.M.; Olden, M.; Rayner, N.W.; Renstrom, F.; Ried, J.S.; Robertson, N.R.; Rose, L.M.; Sanna, S.; Scharnagl, H.; Scholtens, S.; Sennblad, B.; Seufferlein, T.; Sitlani, C.M.; Vernon Smith, A.; Stirrups, K.; Stringham, H.M.; Sundstrom, J.; Swertz, M.A.; Swift, A.J.; Syvanen, A.C.; Tayo, B.O.; Thorand, B.; Thorleifsson, G.; Tomaschitz, A.; Troffa, C.; van Oort, F.V.; Verweij, N.; Vonk, J.M.; Waite, L.L.; Wennauer, R.; Wilsgaard, T.; Wojczynski, M.K.; Wong, A.; Zhang, Q.; Hua Zhao, J.; Brennan, E.P.; Choi, M.; Eriksson, P.; Folkersen, L.; Franco-Cereceda, A.; Gharavi, A.G.; Hedman, A.K.; Hivert, M.F.; Huang, J.; Kanoni, S.; Karpe, F.; Keildson, S.; Kiryluk, K.; Liang, L.; Lifton, R.P.; Ma, B.; McKnight, A.J.; McPherson, R.; Metspalu, A.; Min, J.L.; Moffatt, M.F.; Montgomery, G.W.; Murabito, J.M.; Nicholson, G.; Nyholt, D.R.; Olsson, C.; Perry, J.R.; Reinmaa, E.; Salem, R.M.; Sandholm, N.; Schadt, E.E.; Scott, R.A.; Stolk, L.; Vallejo, E.E.; Westra, H.J.; Zondervan, K.T.; Consortium, A.D.I.P.O.G.; Consortium, C.A.R.D.I.O.G.R.A.M.C.4D.; Consortium, C.K.D.G.; Consortium, G.; Consortium, G.; Glgc; Icbp; International Endogene, C.; LifeLines Cohort, S.; Investigators, M.; Mu, T.C.; Consortium, P.; ReproGen, C.; Amouyel, P.; Arveiler, D.; Bakker, S.J.; Beilby, J.; Bergman, R.N.; Blangero, J.; Brown, M.J.; Burnier, M.; Campbell, H.; Chakravarti, A.; Chines, P.S.; Claudi-Boehm, S.; Collins, F.S.; Crawford, D.C.; Danesh, J.; de Faire, U.; de Geus, E.J.; Dorr, M.; Erbel, R.; Eriksson, J.G.; Farrall, M.; Ferrannini, E.; Ferrieres, J.; Forouhi, N.G.; Forrester, T.; Franco, O.H.; Gansevoort, R.T.; Gieger, C.; Gudnason, V.; Haiman, C.A.; Harris, T.B.; Hattersley, A.T.; Heliovaara, M.; Hicks, A.A.; Hingorani, A.D.; Hoffmann, W.; Hofman, A.; Homuth, G.; Humphries, S.E.; Hypponen, E.; Illig, T.; Jarvelin, M.R.; Johansen, B.; Jousilahti, P.; Jula, A.M.; Kaprio, J.; Kee, F.; Keinanen-Kiukaanniemi, S.M.; Kooner, J.S.; Kooperberg, C.; Kovacs, P.; Kraja, A.T.; Kumari, M.; Kuulasmaa, K.; Kuusisto, J.; Lakka, T.A.; Langenberg, C.; Le Marchand, L.; Lehtimaki, T.; Lyssenko, V.; Mannisto, S.; Marette, A.; Matise, T.C.; McKenzie, C.A.; McKnight, B.; Musk, A.W.; Mohlenkamp, S.; Morris, A.D.; Nelis, M.; Ohlsson, C.; Oldehinkel, A.J.; Ong, K.K.; Palmer, L.J.; Penninx, B.W.; Peters, A.; Pramstaller, P.P.; Raitakari, O.T.; Rankinen, T.; Rao, D.C.; Rice, T.K.; Ridker, P.M.; Ritchie, M.D.; Rudan, I.; Salomaa, V.; Samani, N.J.; Saramies, J.; Sarzynski, M.A.; Schwarz, P.E.; Shuldiner, A.R.; Staessen, J.A.; Steinthorsdottir, V.; Stolk, R.P.; Strauch, K.; Tonjes, A.; Tremblay, A.; Tremoli, E.; Vohl, M.C.; Volker, U.; Vollenweider, P.; Wilson, J.F.; Witteman, J.C.; Adair, L.S.; Bochud, M.; Boehm, B.O.; Bornstein, S.R.; Bouchard, C.; Cauchi, S.; Caulfield, M.J.; Chambers, J.C.; Chasman, D.I.; Cooper, R.S.; Dedoussis, G.; Ferrucci, L.; Froguel, P.; Grabe, H.J.; Hamsten, A.; Hui, J.; Hveem, K.; Jockel, K.H.; Kivimaki, M.; Kuh, D.; Laakso, M.; Liu, Y.; Marz, W.; Munroe, P.B.; Njolstad, I.; Oostra, B.A.; Palmer, C.N.; Pedersen, N.L.; Perola, M.; Perusse, L.; Peters, U.; Power, C.; Quertermous, T.; Rauramaa, R.; Rivadeneira, F.; Saaristo, T.E.; Saleheen, D.; Sinisalo, J.; Slagboom, P.E.; Snieder, H.; Spector, T.D.; Thorsteinsdottir, U.; Stumvoll, M.; Tuomilehto, J.; Uitterlinden, A.G.; Uusitupa, M.; van der Harst, P.; Veronesi, G.; Walker, M.; Wareham, N.J.; Watkins, H.; Wichmann, H.E.; Abecasis, G.R.; Assimes, T.L.; Berndt, S.I.; Boehnke, M.; Borecki, I.B.; Deloukas, P.; Franke, L.; Frayling, T.M.; Groop, L.C.; Hunter, D.J.; Kaplan, R.C.; O'Connell, J.R.; Qi, L.; Schlessinger, D.; Strachan, D.P.; Stefansson, K.; van Duijn, C.M.; Willer, C.J.; Visscher, P.M.; Yang, J.; Hirschhorn, J.N.; Zillikens, M.C.; McCarthy, M.I.; Speliotes, E.K.; North, K.E.; Fox, C.S.; Barroso, I.; Franks, P.W.; Ingelsson, E.; Heid, I.M.; Loos, R.J.; Cupples, L.A.; Morris, A.P.; Lindgren, C.M.; Mohlke, K.L.   
  Title New genetic loci link adipose and insulin biology to body fat distribution Type Journal Article
  Year 2015 Publication Nature Abbreviated Journal Nature  
  Volume 518 Issue 7538 Pages 187-196  
  Keywords HUNT3; Adipocytes/metabolism; Adipogenesis/genetics; Adipose Tissue/*metabolism; Age Factors; *Body Fat Distribution; Body Mass Index; Continental Population Groups/genetics; Epigenesis, Genetic; Europe/ethnology; Female; Genome, Human/genetics; *Genome-Wide Association Study; Humans; Insulin/*metabolism; Insulin Resistance/genetics; Male; Models, Biological; Neovascularization, Physiologic/genetics; Obesity/genetics; Polymorphism, Single Nucleotide/genetics; Quantitative Trait Loci/*genetics; Sex Characteristics; Transcription, Genetic/genetics; Waist-Hip Ratio  
  Abstract Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication 1] Department of Public Health and Clinical Medicine, Unit of Medicine, Umea University, 901 87 Umea 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 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Shungin2015 Serial 1858  
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