Journal article
Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
Leukemia, Vol.36(12), pp.2835-2844
12/2022
DOI: 10.1038/s41375-022-01711-0
PMCID: PMC10337695
PMID: 36273105
Abstract
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
) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10
). 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
), 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.
Details
- Title: Subtitle
- Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
- Creators
- Sonja I Berndt - National Cancer InstituteJoseph Vijai - Memorial Sloan Kettering Cancer CenterYolanda Benavente - Centro de Investigación Biomédica en Red de Epidemiología y Salud PúblicaNicola J Camp - Huntsman Cancer InstituteAlexandra Nieters - University Medical Center FreiburgZhaoming Wang - St. Jude Children's Research HospitalKarin E Smedby - Karolinska InstitutetGeffen Kleinstern - University of HaifaHenrik Hjalgrim - Statens Serum InstitutCaroline Besson - Centre Hospitalier de VersaillesChristine F Skibola - Emory UniversityLindsay M Morton - National Cancer InstituteAngela R Brooks-Wilson - BC Cancer AgencyLauren R Teras - American Cancer SocietyCharles Breeze - National Cancer InstituteJoshua Arias - National Cancer InstituteHans-Olov Adami - Karolinska InstitutetDemetrius Albanes - National Cancer InstituteKenneth C Anderson - Dana-Farber Cancer InstituteStephen M Ansell - Mayo ClinicBryan Bassig - National Cancer InstituteNikolaus Becker - German Cancer Research CenterParveen Bhatti - Fred Hutch Cancer CenterBrenda M Birmann - Brigham and Women's HospitalPaolo Boffetta - Stony Brook UniversityPaige M Bracci - University of California, San FranciscoPaul Brennan - Centre international de recherche sur le cancerElizabeth E Brown - University of Alabama at BirminghamLaurie Burdett - National Cancer InstituteLisa A Cannon-Albright - Huntsman Cancer InstituteEllen T Chang - University of California, San FranciscoBrian C H Chiu - Chicago Department of Public HealthCharles C Chung - National Cancer InstituteJacqueline Clavel - InsermPierluigi Cocco - University of ManchesterGraham Colditz - Washington University in St. LouisLucia Conde - University College LondonDavid V Conti - University of Southern CaliforniaDavid G Cox - Centre de Recherche en Cancérologie de LyonKaren Curtin - Huntsman Cancer InstituteDelphine Casabonne - Institut Català d'OncologiaImmaculata De Vivo - Harvard UniversityArjan Diepstra - University Medical Center GroningenW Ryan Diver - American Cancer SocietyAhmet Dogan - Memorial Sloan Kettering Cancer CenterChristopher K Edlund - University of Southern CaliforniaLenka Foretova - Masaryk Memorial Cancer InstituteJoseph F Fraumeni Jr - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md, USAAttilio Gabbas - University of CagliariHervé Ghesquières - Hospices Civils de LyonGraham G Giles - Monash UniversitySally Glaser - Cancer Prevention Institute of CaliforniaMartha Glenn - Huntsman Cancer InstituteBengt Glimelius - Uppsala UniversityJian Gu - The University of Texas MD Anderson Cancer CenterThomas M Habermann - Mayo ClinicChristopher A Haiman - University of Southern CaliforniaCorinne Haioun - Université Paris-Est CréteilJonathan N Hofmann - National Cancer InstituteTheodore R Holford - Yale UniversityElizabeth A Holly - University of California, San FranciscoAmy Hutchinson - National Cancer InstituteAalin Izhar - Memorial Sloan Kettering Cancer CenterRebecca D Jackson - The Ohio State UniversityRuth F Jarrett - MRC University of Glasgow Centre for Virus ResearchRudolph Kaaks - German Cancer Research CenterEleanor Kane - University of YorkLaurence N Kolonel - Cancer Center of HawaiiYinfei Kong - California State University, FullertonPeter Kraft - Harvard UniversityAnne Kricker - The University of SydneyAnnette Lake - MRC University of Glasgow Centre for Virus ResearchQing Lan - National Cancer InstituteCharles Lawrence - Westat (United States)Dalin Li - Cedars-Sinai Medical CenterMark Liebow - Mayo Clinic in FloridaBrian K Link - University of IowaCorrado Magnani - Università degli Studi del Piemonte Orientale “Amedeo Avogadro”Marc Maynadie - Université de BourgogneJames McKay - Centre international de recherche sur le cancerMads Melbye - Stanford UniversityLucia Miligi - Piedmont Reference Center for Epidemiology and Cancer PreventionRoger L Milne - Cancer Council VictoriaThierry J Molina - Université Paris CitéAlain Monnereau - InsermRebecca Montalvan - Westat (United States)Kari E North - University of North Carolina at Chapel HillAnne J Novak - Mayo ClinicKenan Onel - Donald & Barbara Zucker School of Medicine at Hofstra/NorthwellMark P Purdue - National Cancer InstituteKristin A Rand - University of Southern CaliforniaElio Riboli - Imperial College LondonJacques Riby - University of Alabama at BirminghamEve Roman - University of YorkGilles Salles - Memorial Sloan Kettering Cancer CenterDouglas W Sborov - Huntsman Cancer InstituteRichard K Severson - Wayne State UniversityTait D Shanafelt - Stanford UniversityMartyn T Smith - University of California, BerkeleyAlexandra Smith - University of YorkKevin W Song - BC Cancer AgencyLei Song - Center for Cancer Research, National Cancer Institute, Frederick, MA, USA.Melissa C Southey - Cancer Council VictoriaJohn J Spinelli - University of British ColumbiaAnthony Staines - Dublin City UniversityDeborah Stephens - Huntsman Cancer InstituteHeather J Sutherland - BC Cancer AgencyKaitlyn Tkachuk - Memorial Sloan Kettering Cancer CenterCarrie A Thompson - Mayo ClinicHervé Tilly - Université de Rouen NormandieLesley F Tinker - Fred Hutch Cancer CenterRuth C Travis - University of OxfordJenny Turner - Macquarie UniversityCeline M Vachon - Mayo ClinicClaire M Vajdic - UNSW SydneyAnke Van Den Berg - University Medical Center GroningenDavid J Van Den Berg - University of Southern CaliforniaRoel C H Vermeulen - University Medical Center UtrechtPaolo Vineis - Imperial College LondonSophia S Wang - City Of Hope National Medical CenterElisabete Weiderpass - Centre international de recherche sur le cancerGeorge J Weiner - University of IowaStephanie Weinstein - National Cancer InstituteNicole Wong Doo - The University of SydneyYuanqing Ye - The University of Texas MD Anderson Cancer CenterMeredith Yeager - National Cancer InstituteKai Yu - National Cancer InstituteAnne Zeleniuch-Jacquotte - New York UniversityYawei Zhang - Yale UniversityTongzhang Zheng - Brown UniversityElad Ziv - UCSF Helen Diller Family Comprehensive Cancer CenterJoshua Sampson - National Cancer InstituteNilanjan Chatterjee - Johns Hopkins UniversityKenneth Offit - Memorial Sloan Kettering Cancer CenterWendy Cozen - University of California, IrvineXifeng Wu - The University of Texas MD Anderson Cancer CenterJames R Cerhan - Mayo Clinic in FloridaStephen J Chanock - National Cancer InstituteSusan L Slager - Mayo Clinic in FloridaNathaniel Rothman - National Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Leukemia, Vol.36(12), pp.2835-2844
- DOI
- 10.1038/s41375-022-01711-0
- PMID
- 36273105
- PMCID
- PMC10337695
- NLM abbreviation
- Leukemia
- ISSN
- 0887-6924
- eISSN
- 1476-5551
- Grant note
- UM1 CA167552 / NCI NIH HHS P01 CA087969 / NCI NIH HHS K08 CA134919 / NCI NIH HHS UM1 CA186107 / NCI NIH HHS P30 CA015083 / NCI NIH HHS P50 CA097274 / NCI NIH HHS U01 CA049449 / NCI NIH HHS R01 CA098122 / NCI NIH HHS R01 CA149445 / NCI NIH HHS R01 CA134674 / NCI NIH HHS R01 CA049449 / NCI NIH HHS R01 CA148690 / NCI NIH HHS U01 CA118444 / NCI NIH HHS P30 CA016087 / NCI NIH HHS
- Language
- English
- Date published
- 12/2022
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984359783402771
Metrics
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