Parental origin of sequence variants associated with complex diseases View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-12

AUTHORS

Augustine Kong, Valgerdur Steinthorsdottir, Gisli Masson, Gudmar Thorleifsson, Patrick Sulem, Soren Besenbacher, Aslaug Jonasdottir, Asgeir Sigurdsson, Kari Th. Kristinsson, Adalbjorg Jonasdottir, Michael L. Frigge, Arnaldur Gylfason, Pall I. Olason, Sigurjon A. Gudjonsson, Sverrir Sverrisson, Simon N. Stacey, Bardur Sigurgeirsson, Kristrun R. Benediktsdottir, Helgi Sigurdsson, Thorvaldur Jonsson, Rafn Benediktsson, Jon H. Olafsson, Oskar Th. Johannsson, Astradur B. Hreidarsson, Gunnar Sigurdsson, DIAGRAM Consortium, Benjamin F. Voight, Laura J. Scott, Christian Dina, Eleftheria Zeggini, Cornelia Huth, Yurii S. Aulchenko, Ryan P. Welch, Laura J. McCulloch, Teresa Ferreira, Harald Grallert, Najaf Amin, Guanming Wu, Cristen J. Willer, Soumya Raychaudhuri, Shaun Purcell, Steve A. McCarroll, Claudia Langenberg, Oliver M. Hoffmann, Josée Dupuis, Lu Qi, Ayellet V. Segrè, Mandy van Hoek, Pau Navarro, Kristin Ardlie, Beverley Balkau, Amanda J. Bennett, Roza Blagieva, Eric Boerwinkle, Lori L. Bonnycastle, Kristina Bengtsson Boström, Bert Bravenboer, Suzannah Bumpstead, Noël P. Burtt, Guillaume Charpentier, Peter S. Chines, Marilyn Cornelis, David J. Couper, Gabe Crawford, Alex S. F. Doney, Katherine S. Elliott, Amanda L. Elliott, Michael R. Erdos, Caroline S. Fox, Christopher S. Franklin, Martha Ganser, Christian Gieger, Niels Grarup, Todd Green, Simon Griffin, Christopher J. Groves, Candace Guiducci, Samy Hadjadj, Neelam Hassanali, Christian Herder, Bo Isomaa, Anne U. Jackson, Paul R. V. Johnson, Torben Jørgensen, Wen H. L. Kao, Norman Klopp, Peter Kraft, Johanna Kuusisto, Torsten Lauritzen, Man Li, Alouisius Lieverse, Cecilia M. Lindgren, Valeriya Lyssenko, Michel Marre, Thomas Meitinger, Kristian Midthjell, Mario A Morken, Narisu Narisu, Peter Nilsson, Katharine R. Owen, Felicity Payne, John R. B. Perry, Ann-Kristin Petersen, Carl Platou, Christine Proença, Inga Prokopenko, Wolfgang Rathmann, N. William Rayner, Neil R. Robertson, Ghislain Rocheleau, Michael Roden, Michael J. Sampson, Richa Saxena, Beverley M. Shields, Peter Shrader, Nicholas Smith, Thomas Sparsø, Klaus Strassburger, Heather M. Stringham, Qi Sun, Amy J. Swift, Barbara Thorand, Jean Tichet, Tiinamaija Tuomi, Rob van Dam, Thijs van Herpt, G. Bragi Walters, Michael N. Weedon, Jacqueline Witteman, Richard N. Bergman, Stephane Cauchi, Francis S. Collins, Anna L. Gloyn, Ulf Gyllensten, Torben Hansen, Winston A. Hide, Graham A. Hitman, Albert Hofman, David Hunter, Kristian Hveem, Markku Laakso, Karen L. Mohlke, Andrew D. Morris, Colin N. A. Palmer, Peter P. Pramstaller, Igor Rudan, Eric Sijbrands, Lincoln D. Stein, Jaakko Tuomilehto, Andre Uitterlinden, Mark Walker, Nicholas J. Wareham, Richard M. Watanabe, Goncalo R. Abecasis, Inês Barroso, Bernhard O. Boehm, Harry Campbell, Mark J. Daly, Jose C. Florez, Timothy M. Frayling, Leif Groop, Andrew T. Hattersley, Frank B. Hu, James B. Meigs, Andrew P. Morris, James S. Pankow, Oluf Pedersen, Rob Sladek, Unnur Thorsteinsdottir, H.-Erich Wichmann, James F. Wilson, Thomas Illig, Philippe Froguel, Cornelia M. van Duijn, Kari Stefansson, David Altshuler, Michael Boehnke, Mark I. McCarthy., Anne C. Ferguson-Smith, Daniel F. Gudbjartsson

ABSTRACT

Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site. More... »

PAGES

868

Journal

TITLE

Nature

ISSUE

7275

VOLUME

462

Author Affiliations

  • deCODE Genetics (Iceland)
  • Icelandic Heart Association
  • National University Hospital of Iceland
  • Harvard University
  • University of Michigan–Ann Arbor
  • Délégation Grand-Ouest
  • Wellcome Centre for Human Genetics
  • Ludwig Maximilian University of Munich
  • Erasmus University Medical Center
  • University of Oxford
  • Ontario Institute for Cancer Research
  • Massachusetts General Hospital
  • Broad Institute
  • Boston University
  • Western General Hospital
  • University of Paris-Sud
  • University Hospital Ulm
  • The University of Texas Health Science Center at Houston
  • Catharina Ziekenhuis
  • Wellcome Sanger Institute
  • University of North Carolina at Chapel Hill
  • National Heart Lung and Blood Institute
  • University of Edinburgh
  • Novo Nordisk (Denmark)
  • German Diabetes Center - Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf
  • Folkhälsans Forskningscentrum
  • Rigshospitalet
  • Johns Hopkins University
  • Kuopio University Hospital
  • Aarhus University
  • Paris Diderot University
  • Norwegian University of Science and Technology
  • University of Exeter
  • McGill University and Génome Québec Innovation Centre
  • Heinrich Heine University Düsseldorf
  • Norfolk and Norwich University Hospitals NHS Foundation Trust
  • University of Southern California
  • National Institutes of Health
  • Uppsala University
  • University of Southern Denmark
  • Royal London Hospital
  • European Academy of Bozen
  • Sisters of Charity Hospital
  • National Institute for Health and Welfare
  • Newcastle University
  • University of Minnesota
  • University of Iceland
  • Imperial College London
  • Churchill Hospital
  • University of Cambridge
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature08625

    DOI

    http://dx.doi.org/10.1038/nature08625

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1017956321

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20016592


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