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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
SI. Berndt, J. Vijai, Y. Benavente, NJ. Camp, A. Nieters, Z. Wang, KE. Smedby, G. Kleinstern, H. Hjalgrim, C. Besson, CF. Skibola, LM. Morton, AR. Brooks-Wilson, LR. Teras, C. Breeze, J. Arias, HO. Adami, D. Albanes, KC. Anderson, SM. Ansell, B....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, Research Support, N.I.H., Intramural, Research Support, N.I.H., Extramural
Grantová podpora
P01 CA087969
NCI NIH HHS - United States
R01 CA148690
NCI NIH HHS - United States
K08 CA134919
NCI NIH HHS - United States
UM1 CA186107
NCI NIH HHS - United States
P30 CA015083
NCI NIH HHS - United States
UM1 CA167552
NCI NIH HHS - United States
P50 CA097274
NCI NIH HHS - United States
R01 CA049449
NCI NIH HHS - United States
R01 CA134674
NCI NIH HHS - United States
U01 CA118444
NCI NIH HHS - United States
P30 CA016087
NCI NIH HHS - United States
R01 CA098122
NCI NIH HHS - United States
U01 CA049449
NCI NIH HHS - United States
R01 CA149445
NCI NIH HHS - United States
NLK
ProQuest Central
od 2000-01-01 do Před 1 rokem
Open Access Digital Library
od 1997-01-01
Nursing & Allied Health Database (ProQuest)
od 2000-01-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 2000-01-01 do Před 1 rokem
Public Health Database (ProQuest)
od 2000-01-01 do Před 1 rokem
- MeSH
- celogenomová asociační studie MeSH
- genetická predispozice k nemoci * MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- nehodgkinský lymfom * genetika MeSH
- rizikové faktory MeSH
- studie případů a kontrol MeSH
- zárodečné buňky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10-8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10-9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10-8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
Bill Lyons Informatics Centre UCL Cancer Institute University College London London United Kingdom
Cancer Control Research BC Cancer Agency Vancouver BC Canada
Cancer Epidemiology Division Cancer Council Victoria Melbourne VC Australia
Cancer Epidemiology Program University of Hawaii Cancer Center Honolulu HI USA
Cancer Epidemiology Unit University of Oxford Oxford United Kingdom
Cancer Prevention Institute of California Fremont CA USA
Carolina Center for Genome Sciences University of North Carolina at Chapel Hill Chapel Hill NC USA
Center for Cancer Research National Cancer Institute Frederick MA USA
Center for Health Sciences Exponent Inc Menlo Park CA USA
Centre Henri Becquerel Université de Rouen Rouen France
Centre Hospitalier de Versailles Le Chesnay France
Chao Family Comprehensive Cancer Center University of California Irvine Irvine CA USA
CIBER de Epidemiología y Salud Pública Barcelona Spain
Concord Clinical School University of Sydney Concord NSW Australia
CRESS UMR1153 INSERM Villejuif France
Danish Cancer Society Research Center Copenhagen Denmark
Danish Cancer Society Research Center Danish Cancer Society Copenhagen Denmark
Department of Biomedical Physiology and Kinesiology Simon Fraser University Burnaby BC Canada
Department of Biostatistics Harvard T H Chan School of Public Health Boston MA USA
Department of Biostatistics Yale School of Public Health New Haven CT USA
Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Clinical Medicine University of Copenhagen Copenhagen Denmark
Department of Environmental Health Sciences Yale School of Public Health New Haven CT USA
Department of Environmental Medicine New York University School of Medicine New York NY USA
Department of Epidemiology and Cancer Control St Jude Children's Research Hospital Memphis TN USA
Department of Epidemiology Brown University Providence RI USA
Department of Epidemiology Harvard T H Chan School of Public Health Boston MA USA
Department of Epidemiology MD Anderson Cancer Center Houston TX USA
Department of Epidemiology University of North Carolina at Chapel Hill Chapel Hill NC USA
Department of Family Medicine and Public Health Sciences Wayne State University Detroit MI USA
Department of Genetics Stanford University Medical School Stanford CA USA
Department of Haematology Rigshospitalet Copenhagen Denmark
Department of Health Sciences Research Mayo Clinic Rochester MN USA
Department of Health Sciences University of York York United Kingdom
Department of Hematology and Medical Oncology Emory University School of Medicine Atlanta GA USA
Department of Hematology Hospices Civils de Lyon Lyon Sud Hospital Pierre Benite France
Department of Histopathology Douglass Hanly Moir Pathology Sydney NSW Australia
Department of Immunology Genetics and Pathology Uppsala University Uppsala Sweden
Department of Internal Medicine Carver College of Medicine The University of Iowa Iowa City IA USA
Department of Internal Medicine Mayo Clinic Rochester MN USA
Department of Medical and Surgical Sciences University of Bologna Bologna 41026 Italy
Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
Department of Medical Oncology Dana Farber Cancer Institute Harvard Medical School Boston MA USA
Department of Medicine Memorial Sloan Kettering Cancer Center New York NY USA
Department of Medicine Solna Karolinska Institutet Stockholm Sweden
Department of Medicine Stanford University School of Medicine Stanford CA USA
Department of Medicine University of British Columbia Vancouver BC Canada
Department of Oncology School of Medicine Johns Hopkins University Baltimore MA USA
Department of Pathology University of Alabama at Birmingham Birmingham AL USA
Department of Population Health New York University School of Medicine New York NY USA
Department of Population Science American Cancer Society Atlanta GA USA
Department of Public Health Sciences University of Chicago Chicago IL USA
Department of Quantitative Health Sciences Mayo Clinic Rochester MN USA
Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda Md USA
Division of Cancer Epidemiology German Cancer Research Center Heidelberg Baden Württemberg Germany
Division of Endocrinology Diabetes and Metabolism The Ohio State University Columbus OH USA
Division of Health Analytics City of Hope Beckman Research Institute Duarte CA USA
Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle WA USA
Donald and Barbara Zucker School of Medicine Hofstra Northwell Hempstead New York NY USA
Faculty of Medicine and Health Sciences Macquarie University Sydney NSW Australia
Genome Sciences Centre BC Cancer Agency Vancouver BC Canada
George E Wahlen Department of Veterans Affairs Medical Center Salt Lake City UT USA
Hematology Center Karolinska University Hospital Stockholm Sweden
Human Genetics Foundation Turin Italy
Information Systems and Decision Sciences California State University Fullerton Fullerton CA USA
INSERM U1052 Cancer Research Center of Lyon Centre Léon Bérard Lyon France
Institute for Immunodeficiency University Medical Center Freiburg Freiburg Germany
Institute for Risk Assessment Sciences Utrecht University Utrecht The Netherlands
Institute of Health and Society Clinical Effectiveness Research Group University of Oslo Oslo Norway
International Agency for Research on Cancer Lyon France
Jebsen Center for Genetic epidemiology NTNU Trondheim Norway
Leukemia Bone Marrow Transplantation Program BC Cancer Agency Vancouver BC Canada
Lymphoid Malignancies Unit Henri Mondor Hospital and University Paris Est Créteil France
MRC University of Glasgow Centre for Virus Research Glasgow United Kingdom
Perlmutter Cancer Center NYU Langone Medical Center New York NY USA
Registre des hémopathies malignes de la Gironde Institut Bergonié Bordeaux Cedex France
School of Nursing Psychotherapy and Community Health Dublin City University Dublin Ireland
School of Population and Public Health University of British Columbia Vancouver BC Canada
School of Public Health Imperial College London London United Kingdom
School of Public Health University of Haifa Haifa Israel
Stanford Cancer Institute Stanford CA USA
Stony Brook Cancer Center Stony Brook University Stony Brook New York 11794 NY USA
Sydney School of Public Health The University of Sydney Sydney NSW Australia
The Kirby Institute University of New South Wales Sydney NSW Australia
Université de Paris Cité Villejuif France
Université Paris Saclay UVSQ Inserm Équipe Exposome et Hérédité CESP Villejuif France
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- $a Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10-8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10-9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10-8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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