toggle visibility Search & Display Options

Select All    Deselect All
 |   | 
Details
   print
  Records Links
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) Lu, X.; Peloso, G.M.; Liu, D.J.; Wu, Y.; Zhang, H.; Zhou, W.; Li, J.; Tang, C.S.-M.; Dorajoo, R.; Li, H.; Long, J.; Guo, X.; Xu, M.; Spracklen, C.N.; Chen, Y.; Liu, X.; Zhang, Y.; Khor, C.C.; Liu, J.; Sun, L.; Wang, L.; Gao, Y.-T.; Hu, Y.; Yu, K.; Wang, Y.; Cheung, C.Y.Y.; Wang, F.; Huang, J.; Fan, Q.; Cai, Q.; Chen, S.; Shi, J.; Yang, X.; Zhao, W.; Sheu, W.H.-H.; Cherny, S.S.; He, M.; Feranil, A.B.; Adair, L.S.; Gordon-Larsen, P.; Du, S.; Varma, R.; Chen, Y.-D.I.; Shu, X.-O.; Lam, K.S.L.; Wong, T.Y.; Ganesh, S.K.; Mo, Z.; Hveem, K.; Fritsche, L.G.; Nielsen, J.B.; Tse, H.-F.; Huo, Y.; Cheng, C.-Y.; Chen, Y.E.; Zheng, W.; Tai, E.S.; Gao, W.; Lin, X.; Huang, W.; Abecasis, G.; Kathiresan, S.; Mohlke, K.L.; Wu, T.; Sham, P.C.; Gu, D.; Willer, C.J. url  doi
  Title Exome chip meta-analysis identifies novel loci and East Asian-specific coding variants that contribute to lipid levels and coronary artery disease Type Meta-Analysis
  Year 2017 Publication Nature Genetics Abbreviated Journal Nat Genet  
  Volume 49 Issue 12 Pages 1722-1730  
  Keywords Asian Continental Ancestry Group/genetics; Coronary Artery Disease/ethnology/*genetics; Europe; European Continental Ancestry Group/genetics; Exome/*genetics; Far East; Gene Frequency; Genetic Predisposition to Disease/ethnology/*genetics; *Genetic Variation; Genome-Wide Association Study; Genotype; Humans; Lipid Metabolism/*genetics; Lipids/analysis  
  Abstract Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.  
  Address Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA  
  Corporate Author GLGC 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 1061-4036 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:29083407 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1957  
Permanent link to this record
Select All    Deselect All
 |   | 
Details
   print

Save Citations:
Export Records: