例如："lncRNA", "apoptosis", "WRKY"

Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.

Am J Hum Genet. 2014 Oct 02;95(4):462-71
Christine F Skibola 1 , Sonja I Berndt 2 , Joseph Vijai 3 , Lucia Conde 4 , Zhaoming Wang 5 , Meredith Yeager 5 , Paul I W de Bakker 6 , Brenda M Birmann 7 , Claire M Vajdic 8 , Jia-Nee Foo 9 , Paige M Bracci 10 , Roel C H Vermeulen 11 , Susan L Slager 12 , Silvia de Sanjose 13 , Sophia S Wang 14 , Martha S Linet 2 , Gilles Salles 15 , Qing Lan 2 , Gianluca Severi 16 , Henrik Hjalgrim 17 , Tracy Lightfoot 18 , Mads Melbye 19 , Jian Gu 20 , Hervé Ghesquières 21 , Brian K Link 22 , Lindsay M Morton 2 , Elizabeth A Holly 10 , Alex Smith 18 , Lesley F Tinker 23 , Lauren R Teras 24 , Anne Kricker 25 , Nikolaus Becker 26 , Mark P Purdue 2 , John J Spinelli 27 , Yawei Zhang 28 , Graham G Giles 29 , Paolo Vineis 30 , Alain Monnereau 31 , Kimberly A Bertrand 32 , Demetrius Albanes 2 , Anne Zeleniuch-Jacquotte 33 , Attilio Gabbas 34 , Charles C Chung 2 , Laurie Burdett 5 , Amy Hutchinson 5 , Charles Lawrence 35 , Rebecca Montalvan 35 , Liming Liang 36 , Jinyan Huang 37 , Baoshan Ma 38 , Jianjun Liu 9 , Hans-Olov Adami 39 , Bengt Glimelius 40 , Yuanqing Ye 20 , Grzegorz S Nowakowski 12 , Ahmet Dogan 41 , Carrie A Thompson 42 , Thomas M Habermann 42 , Anne J Novak 42 , Mark Liebow 42 , Thomas E Witzig 42 , George J Weiner 22 , Maryjean Schenk 43 , Patricia Hartge 2 , Anneclaire J De Roos 44 , Wendy Cozen 45 , Degui Zhi 46 , Nicholas K Akers 47 , Jacques Riby 4 , Martyn T Smith 47 , Mortimer Lacher 3 , Danylo J Villano 3 , Ann Maria 3 , Eve Roman 18 , Eleanor Kane 18 , Rebecca D Jackson 48 , Kari E North 49 , W Ryan Diver 24 , Jenny Turner 50 , Bruce K Armstrong 25 , Yolanda Benavente 13 , Paolo Boffetta 51 , Paul Brennan 52 , Lenka Foretova 53 , Marc Maynadie 54 , Anthony Staines 55 , James McKay 56 , Angela R Brooks-Wilson 57 , Tongzhang Zheng 28 , Theodore R Holford 58 , Saioa Chamosa 59 , Rudolph Kaaks 26 , Rachel S Kelly 60 , Bodil Ohlsson 61 , Ruth C Travis 62 , Elisabete Weiderpass 63 , Jacqueline Clavel 64 , Edward Giovannucci 65 , Peter Kraft 36 , Jarmo Virtamo 66 , Patrizio Mazza 67 , Pierluigi Cocco 34 , Maria Grazia Ennas 68 , Brian C H Chiu 69 , Joseph F Fraumeni 2 , Alexandra Nieters 70 , Kenneth Offit 3 , Xifeng Wu 20 , James R Cerhan 12 , Karin E Smedby 71 , Stephen J Chanock 2 , Nathaniel Rothman 2
Christine F Skibola 1 , Sonja I Berndt 2 , Joseph Vijai 3 , Lucia Conde 4 , Zhaoming Wang 5 , Meredith Yeager 5 , Paul I W de Bakker 6 , Brenda M Birmann 7 , Claire M Vajdic 8 , Jia-Nee Foo 9 , Paige M Bracci 10 , Roel C H Vermeulen 11 , Susan L Slager 12 , Silvia de Sanjose 13 , Sophia S Wang 14 , Martha S Linet 2 , Gilles Salles 15 , Qing Lan 2 , Gianluca Severi 16 , Henrik Hjalgrim 17 , Tracy Lightfoot 18 , Mads Melbye 19 , Jian Gu 20 , Hervé Ghesquières 21 , Brian K Link 22 , Lindsay M Morton 2 , Elizabeth A Holly 10 , Alex Smith 18 , Lesley F Tinker 23 , Lauren R Teras 24 , Anne Kricker 25 , Nikolaus Becker 26 , Mark P Purdue 2 , John J Spinelli 27 , Yawei Zhang 28 , Graham G Giles 29 , Paolo Vineis 30 , Alain Monnereau 31 , Kimberly A Bertrand 32 , Demetrius Albanes 2 , Anne Zeleniuch-Jacquotte 33 , Attilio Gabbas 34 , Charles C Chung 2 , Laurie Burdett 5 , Amy Hutchinson 5 , Charles Lawrence 35 , Rebecca Montalvan 35 , Liming Liang 36 , Jinyan Huang 37 , Baoshan Ma 38 , Jianjun Liu 9 , Hans-Olov Adami 39 , Bengt Glimelius 40 , Yuanqing Ye 20 , Grzegorz S Nowakowski 12 , Ahmet Dogan 41 , Carrie A Thompson 42 , Thomas M Habermann 42 , Anne J Novak 42 , Mark Liebow 42 , Thomas E Witzig 42 , George J Weiner 22 , Maryjean Schenk 43 , Patricia Hartge 2 , Anneclaire J De Roos 44 , Wendy Cozen 45 , Degui Zhi 46 , Nicholas K Akers 47 , Jacques Riby 4 , Martyn T Smith 47 , Mortimer Lacher 3 , Danylo J Villano 3 , Ann Maria 3 , Eve Roman 18 , Eleanor Kane 18 , Rebecca D Jackson 48 , Kari E North 49 , W Ryan Diver 24 , Jenny Turner 50 , Bruce K Armstrong 25 , Yolanda Benavente 13 , Paolo Boffetta 51 , Paul Brennan 52 , Lenka Foretova 53 , Marc Maynadie 54 , Anthony Staines 55 , James McKay 56 , Angela R Brooks-Wilson 57 , Tongzhang Zheng 28 , Theodore R Holford 58 , Saioa Chamosa 59 , Rudolph Kaaks 26 , Rachel S Kelly 60 , Bodil Ohlsson 61 , Ruth C Travis 62 , Elisabete Weiderpass 63 , Jacqueline Clavel 64 , Edward Giovannucci 65 , Peter Kraft 36 , Jarmo Virtamo 66 , Patrizio Mazza 67 , Pierluigi Cocco 34 , Maria Grazia Ennas 68 , Brian C H Chiu 69 , Joseph F Fraumeni 2 , Alexandra Nieters 70 , Kenneth Offit 3 , Xifeng Wu 20 , James R Cerhan 12 , Karin E Smedby 71 , Stephen J Chanock 2 , Nathaniel Rothman 2
+ et al

[No authors listed]

Author information
  • 1 Department of Epidemiology, School of Public Health and Comprehensive Cancer Center, Birmingham, AL 35233, USA; Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, CA 94720, USA. Electronic address: cskibola@uab.edu.
  • 2 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • 3 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • 4 Department of Epidemiology, School of Public Health and Comprehensive Cancer Center, Birmingham, AL 35233, USA; Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, CA 94720, USA.
  • 5 Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Gaithersburg, MD 20877, USA.
  • 6 Department of Medical Genetics and of Epidemiology, University Medical Center Utrecht, Utrecht 3584 CG, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands.
  • 7 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • 8 Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.
  • 9 Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore.
  • 10 Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA 94118, USA.
  • 11 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands; Institute for Risk Assessment Sciences, Utrecht University, Utrecht 3508 TD, the Netherlands.
  • 12 Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
  • 13 Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Programme, Institut Catala d'Oncologia, IDIBELL, Barcelona 8907, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona 8036, Spain.
  • 14 Department of Cancer Etiology, City of Hope Beckman Research Institute, Duarte, CA 91030, USA.
  • 15 Department of Hematology, Hospices Civils de Lyon, Pierre benite Cedex 69495, France; Department of Hematology, Université Lyon-1, Pierre benite Cedex 69495, France; Laboratoire de Biologie Moléculaire de la Cellule UMR 5239, Centre National de la Recherche Scientifique, Pierre benite Cedex 69495, France.
  • 16 Human Genetics Foundation, Turin 10126, Italy; Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC 3053, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Carlton, VIC 3010, Australia.
  • 17 Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen 2300, Denmark.
  • 18 Department of Health Sciences, University of York, York YO10 5DD, UK.
  • 19 Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen 2300, Denmark; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 20 Department of Epidemiology, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
  • 21 Laboratoire de Biologie Moléculaire de la Cellule UMR 5239, Centre National de la Recherche Scientifique, Pierre benite Cedex 69495, France; Department of Hematology, Centre Léon Bérard, Lyon 69008, France.
  • 22 Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA.
  • 23 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98117, USA.
  • 24 Epidemiology Research Program, American Cancer Society, Atlanta, GA 30303, USA.
  • 25 Sydney School of Public Health, The University of Sydney, Sydney, NSW 2006, Australia.
  • 26 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg 69120, Germany.
  • 27 Cancer Control Research, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • 28 Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06520, USA.
  • 29 Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC 3053, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Carlton, VIC 3010, Australia.
  • 30 Human Genetics Foundation, Turin 10126, Italy; MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.
  • 31 Environmental Epidemiology of Cancer Group, Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Villejuif Cedex 94807, France; UMRS 1018, Université Paris Sud, Villejuif Cedex 94807, France; Registre des hémopathies malignes de la Gironde, Institut Bergonié, Bordeaux Cedex 33076, France.
  • 32 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
  • 33 Department of Population Health, New York University School of Medicine, New York, NY 10016, USA; Cancer Institute, New York University School of Medicine, New York, NY 10016, USA.
  • 34 Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Monserrato, Cagliari 09042, Italy.
  • 35 Health Studies Sector, Westat, Rockville, MD 20850, USA.
  • 36 Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA; Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
  • 37 Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
  • 38 Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA; College of Information Science and Technology, Dalian Maritime University, Dalian, Liaoning Province 116026, China.
  • 39 Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden.
  • 40 Department of Oncology and Pathology, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm 17176, Sweden; Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala 75105, Sweden.
  • 41 Departments of Laboratory Medicine and Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • 42 Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • 43 Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, MI 48201, USA.
  • 44 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98117, USA; Department of Environmental and Occupational Health, Drexel University School of Public Health, Philadelphia, PA 19104, USA.
  • 45 Department of Preventive Medicine, USC Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • 46 Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
  • 47 Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, CA 94720, USA.
  • 48 Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, OH 43210, USA.
  • 49 Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 50 Department of Anatomical Pathology, Australian School of Advanced Medicine, Macquarie University, Sydney, NSW 2109, Australia; Department of Histopathology, Douglass Hanly Moir Pathology, Macquarie Park, NSW 2113, Australia.
  • 51 The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • 52 Group of Genetic Epidemiology, Section of Genetics, International Agency for Research on Cancer, Lyon 69372, France.
  • 53 Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and MF MU, Brno 656 53, Czech Republic.
  • 54 EA 4184, Registre des Hémopathies Malignes de Côte d'Or, University of Burgundy and Dijon University Hospital, Dijon 21070, France.
  • 55 School of Nursing and Human Sciences, Dublin City University, Dublin 9, Ireland.
  • 56 Genetic Cancer Susceptibility Group, Section of Genetics, International Agency for Research on Cancer, Lyon 69372, France.
  • 57 Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada; Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
  • 58 Department of Biostatistics, Yale School of Public Health, New Haven, CT 06520, USA.
  • 59 Health Department, BioDonostia Research Institute, Basque Region 20014, Spain.
  • 60 MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK; Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
  • 61 Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Lund University, Malmö 205 02, Sweden.
  • 62 Cancer Epidemiology Unit, University of Oxford, Oxford OX3 7LF, UK.
  • 63 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden; Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Breivika 9037, Norway; Cancer Registry of Norway, Oslo 0304, Norway; Department of Genetic Epidemiology, Folkhalsan Research Center, Helsinki 00250, Finland.
  • 64 Environmental Epidemiology of Cancer Group, Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Villejuif Cedex 94807, France; UMRS 1018, Université Paris Sud, Villejuif Cedex 94807, France.
  • 65 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA; Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
  • 66 Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki 00271, Finland.
  • 67 Department of Hematology, Ospedale Nord, Taranto 74100, Italy.
  • 68 Department of Biomedical Science, University of Cagliari, Monserrato, Cagliari 09042, Italy.
  • 69 Department of Health Studies, University of Chicago, Chicago, IL 60637, USA.
  • 70 Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Baden-Württemberg 79108, Germany.
  • 71 Department of Medicine Solna, Karolinska Institutet, Stockholm 17176, Sweden.

摘要

Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.

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