Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes

Lennox Din; Mohammad Sheikh; Nikitha Kosaraju; Karin Ekstrom Smedby; Sasha Bernatsky; Sonja I. Berndt; Christine F. Skibola; Alexandra Nieters; Sophia Wang; James D. McKay; Pierluigi Cocco; Marc Maynadié; Lenka Foretová; Anthony Staines; Thomas M. Mack; Silvia de Sanjosé; Timothy J. Vyse; Leonid Padyukov; Alain Monnereau; Alan A. Arslan; Amy Moore; Angela R. Brooks-Wilson; Anne J. Novak; Bengt Glimelius; Brenda M. Birmann; Brian K. Link; Carolyn Stewart; Claire M. Vajdic; Corinne Haioun; Corrado Magnani; David V. Conti; David G. Cox; Delphine Casabonne; Demetrius Albanes; Eleanor Kane; Eve Roman; Giacomo Muzi; Gilles Salles; Graham G. Giles; Hans Olov Adami; Hervé Ghesquières; Immaculata De Vivo; Jacqueline Clavel; James R. Cerhan; John J. Spinelli; Jonathan Hofmann; Joseph Vijai; Karen Curtin; Karen H. Costenbader; Kenan Onel; Kenneth Offit; Lauren R. Teras; Lindsay Morton; Lucia Conde; Lucia Miligi; Mads Melbye; Maria Grazia Ennas; Mark Liebow; Mark P. Purdue; Martha Glenn; Melissa C. Southey; Morris Din; Nathaniel Rothman; Nicola J. Camp; Nicole Wong Doo; Nikolaus Becker; Nisha Pradhan; Paige M. Bracci; Paolo Boffetta; Paolo Vineis; Paul Brennan; Peter Kraft; Qing Lan; Richard K. Severson; Roel C.H. Vermeulen; Roger L. Milne; Rudolph Kaaks; Ruth C. Travis; Stephanie J. Weinstein; Stephen J. Chanock; Stephen M. Ansell; Susan L. Slager; Tongzhang Zheng; Yawei Zhang; Yolanda Benavente; Zachary Taub; Lohith Madireddy; Pierre Antoine Gourraud; Jorge R. Oksenberg; Wendy Cozen; Henrik Hjalgrim; Pouya Khankhanian

doi:10.1002/gepi.22242

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes

Lennox Din, Mohammad Sheikh, Nikitha Kosaraju, Karin Ekstrom Smedby, Sasha Bernatsky, Sonja I. Berndt, Christine F. Skibola, Alexandra Nieters, Sophia Wang, James D. McKay, Pierluigi Cocco, Marc Maynadié, Lenka Foretová, Anthony Staines, Thomas M. Mack, Silvia de Sanjosé, Timothy J. Vyse, Leonid Padyukov, Alain Monnereau, Alan A. ArslanAmy Moore, Angela R. Brooks-Wilson, Anne J. Novak, Bengt Glimelius, Brenda M. Birmann, Brian K. Link, Carolyn Stewart, Claire M. Vajdic, Corinne Haioun, Corrado Magnani, David V. Conti, David G. Cox, Delphine Casabonne, Demetrius Albanes, Eleanor Kane, Eve Roman, Giacomo Muzi, Gilles Salles, Graham G. Giles, Hans Olov Adami, Hervé Ghesquières, Immaculata De Vivo, Jacqueline Clavel, James R. Cerhan, John J. Spinelli, Jonathan Hofmann, Joseph Vijai, Karen Curtin, Karen H. Costenbader, Kenan Onel, Kenneth Offit, Lauren R. Teras, Lindsay Morton, Lucia Conde, Lucia Miligi, Mads Melbye, Maria Grazia Ennas, Mark Liebow, Mark P. Purdue, Martha Glenn, Melissa C. Southey, Morris Din, Nathaniel Rothman, Nicola J. Camp, Nicole Wong Doo, Nikolaus Becker, Nisha Pradhan, Paige M. Bracci, Paolo Boffetta, Paolo Vineis, Paul Brennan, Peter Kraft, Qing Lan, Richard K. Severson, Roel C.H. Vermeulen, Roger L. Milne, Rudolph Kaaks, Ruth C. Travis, Stephanie J. Weinstein, Stephen J. Chanock, Stephen M. Ansell, Susan L. Slager, Tongzhang Zheng, Yawei Zhang, Yolanda Benavente, Zachary Taub, Lohith Madireddy, Pierre Antoine Gourraud, Jorge R. Oksenberg, Wendy Cozen, Henrik Hjalgrim, Pouya Khankhanian

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p =.0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

Original language	English (US)
Pages (from-to)	844-863
Number of pages	20
Journal	Genetic epidemiology
Volume	43
Issue number	7
DOIs	https://doi.org/10.1002/gepi.22242
State	Published - Oct 1 2019

Keywords

autoimmune disease
genome-wide association study
meta-analysis
non-Hodgkin lymphoma

ASJC Scopus subject areas

Epidemiology
Genetics(clinical)

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10.1002/gepi.22242

Cite this

Din, L., Sheikh, M., Kosaraju, N., Smedby, K. E., Bernatsky, S., Berndt, S. I., Skibola, C. F., Nieters, A., Wang, S., McKay, J. D., Cocco, P., Maynadié, M., Foretová, L., Staines, A., Mack, T. M., de Sanjosé, S., Vyse, T. J., Padyukov, L., Monnereau, A., ... Khankhanian, P. (2019). Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes. Genetic epidemiology, 43(7), 844-863. https://doi.org/10.1002/gepi.22242

Din, L, Sheikh, M, Kosaraju, N, Smedby, KE, Bernatsky, S, Berndt, SI, Skibola, CF, Nieters, A, Wang, S, McKay, JD, Cocco, P, Maynadié, M, Foretová, L, Staines, A, Mack, TM, de Sanjosé, S, Vyse, TJ, Padyukov, L, Monnereau, A, Arslan, AA, Moore, A, Brooks-Wilson, AR, Novak, AJ, Glimelius, B, Birmann, BM, Link, BK, Stewart, C, Vajdic, CM, Haioun, C, Magnani, C, Conti, DV, Cox, DG, Casabonne, D, Albanes, D, Kane, E, Roman, E, Muzi, G, Salles, G, Giles, GG, Adami, HO, Ghesquières, H, De Vivo, I, Clavel, J, Cerhan, JR, Spinelli, JJ, Hofmann, J, Vijai, J, Curtin, K, Costenbader, KH, Onel, K, Offit, K, Teras, LR, Morton, L, Conde, L, Miligi, L, Melbye, M, Ennas, MG, Liebow, M, Purdue, MP, Glenn, M, Southey, MC, Din, M, Rothman, N, Camp, NJ, Wong Doo, N, Becker, N, Pradhan, N, Bracci, PM, Boffetta, P, Vineis, P, Brennan, P, Kraft, P, Lan, Q, Severson, RK, Vermeulen, RCH, Milne, RL, Kaaks, R, Travis, RC, Weinstein, SJ, Chanock, SJ, Ansell, SM , Slager, SL, Zheng, T, Zhang, Y, Benavente, Y, Taub, Z, Madireddy, L, Gourraud, PA, Oksenberg, JR, Cozen, W, Hjalgrim, H & Khankhanian, P 2019, 'Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes', Genetic epidemiology, vol. 43, no. 7, pp. 844-863. https://doi.org/10.1002/gepi.22242

@article{8556206c52f840228f98d9dbd9b16118,

title = "Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes",

abstract = "Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c){"}diseasome{"}, (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p =.0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.",

keywords = "autoimmune disease, genome-wide association study, meta-analysis, non-Hodgkin lymphoma",

author = "Lennox Din and Mohammad Sheikh and Nikitha Kosaraju and Smedby, {Karin Ekstrom} and Sasha Bernatsky and Berndt, {Sonja I.} and Skibola, {Christine F.} and Alexandra Nieters and Sophia Wang and McKay, {James D.} and Pierluigi Cocco and Marc Maynadi{\'e} and Lenka Foretov{\'a} and Anthony Staines and Mack, {Thomas M.} and {de Sanjos{\'e}}, Silvia and Vyse, {Timothy J.} and Leonid Padyukov and Alain Monnereau and Arslan, {Alan A.} and Amy Moore and Brooks-Wilson, {Angela R.} and Novak, {Anne J.} and Bengt Glimelius and Birmann, {Brenda M.} and Link, {Brian K.} and Carolyn Stewart and Vajdic, {Claire M.} and Corinne Haioun and Corrado Magnani and Conti, {David V.} and Cox, {David G.} and Delphine Casabonne and Demetrius Albanes and Eleanor Kane and Eve Roman and Giacomo Muzi and Gilles Salles and Giles, {Graham G.} and Adami, {Hans Olov} and Herv{\'e} Ghesqui{\`e}res and {De Vivo}, Immaculata and Jacqueline Clavel and Cerhan, {James R.} and Spinelli, {John J.} and Jonathan Hofmann and Joseph Vijai and Karen Curtin and Costenbader, {Karen H.} and Kenan Onel and Kenneth Offit and Teras, {Lauren R.} and Lindsay Morton and Lucia Conde and Lucia Miligi and Mads Melbye and Ennas, {Maria Grazia} and Mark Liebow and Purdue, {Mark P.} and Martha Glenn and Southey, {Melissa C.} and Morris Din and Nathaniel Rothman and Camp, {Nicola J.} and {Wong Doo}, Nicole and Nikolaus Becker and Nisha Pradhan and Bracci, {Paige M.} and Paolo Boffetta and Paolo Vineis and Paul Brennan and Peter Kraft and Qing Lan and Severson, {Richard K.} and Vermeulen, {Roel C.H.} and Milne, {Roger L.} and Rudolph Kaaks and Travis, {Ruth C.} and Weinstein, {Stephanie J.} and Chanock, {Stephen J.} and Ansell, {Stephen M.} and Slager, {Susan L.} and Tongzhang Zheng and Yawei Zhang and Yolanda Benavente and Zachary Taub and Lohith Madireddy and Gourraud, {Pierre Antoine} and Oksenberg, {Jorge R.} and Wendy Cozen and Henrik Hjalgrim and Pouya Khankhanian",

note = "Funding Information: WTCCC1: The principal funder of this project was the Wellcome Trust. Case collections were funded by: Arthritis Research Campaign, BDA Research, British Heart Foundation, British Hypertension Society, Diabetes UK, Glaxo‐Smith Kline Research and Development, Juvenile Diabetes Research Foundation, National Association for Colitis and Crohn's disease, SHERT (The Scottish Hospitals Endowment Research Trust), St Bartholomew's and The Royal London Charitable Foundation, UK Medical Research Council, UK NHS R&D and the Wellcome Trust. Statistical analyses were funded by a Commonwealth Scholarship, EU, EPSRC, Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (Portugal), National Institutes of Health, National Science Foundation and the Wellcome Trust. We acknowledge the many physicians, research fellows and research nurses who contributed to the various case collections, and the collection teams and senior management of the UK Blood Services responsible for the UK Blood Services Collection. For the 1958 Birth Cohort, venous blood collection was funded by the UK Medical Research Council and cell‐line production, DNA extraction, and processing by the Juvenile Diabetes Research Foundation and the Wellcome Trust. Funding Information: HPFS (Walter C. Willet): The HPFS was supported in part by National Institutes of Health grants CA167552, CA149445, and CA098122. We would like to thank the participants and staff of the Health Professionals Follow‐up Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. The study protocol was approved by the institutional review boards of the Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. Funding Information: CLL Meta‐Analysis: We thank I. Brock, K. Butterbach, A. Chabrier, D. Chan‐Lam, D. Connley, H. Cramp, R. Cutting, C. Dalley, H. Dykes, A. Gabbas, P. Gaddam, P. Hui, L. Irish, L. Jacobus, S. Kaul, L. Klareskog, A. Lai, J. Lunde, M. McAdams, D. Parisi, V. Rajamanickam, T. Rattle, L. Rigacci, R. Sargent, G. Specchia, M. Stagner, P. Taylor, C. Tornow, J. WiIliams and G. Wood. The overall GWAS project was supported by the intramural program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health. Funding Information: NSW NHL study (C.M.Vajdic): It was supported by grants from the Australian National Health and Medical Research Council (ID990920), the Cancer Council NSW, and the University of Sydney Faculty of Medicine. Funding Information: BC (J.S., A.B.W.): We thank R Gascoyne, J Connors, R Gallagher, T Lee, C Ng, Z Abanto, R Janoo‐Gilani, P Lee, S Leach. A Lai and her study staff, the members of the BC Cancer Agency Lymphoma Tumour Group, and all the participants of the study for making this research possible. The study was supported by grants from the Canadian Institutes for Health Research (CIHR); the Canadian Cancer Society; and the Michael Smith Foundation for Health Research. Funding Information: John J Spinelli is supported by the Canadian Institutes for Health Research (CIHR); the Canadian Cancer Society; and the Michael Smith Foundation for Health Research. Funding Information: Karen H. Costenbader is supported by NIH Grants R01 AR057327, and R01 AR049880. Funding Information: NHS (Meir J. Stampfer): The NHS was supported in part by National Institutes of Health grants CA186107, CA87969, CA49449, CA149445, CA098122, and CA134958. We would like to thank the participants and staff of the Nurses' Health Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. The study protocol was approved by the institutional review boards of the Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. Funding Information: NSFC: the National Natural Science Foundation of China (No. 61471078). Funding Information: WHI: WHI investigators are: Program Office—(National Heart, Lung, and Blood Institute, Bethesda, Maryland) Jacques Rossouw, Shari Ludlam, Dale Burwen, Joan McGowan, Leslie Ford, and Nancy Geller; Clinical Coordinating Center ‐ (Fred Hutchinson Cancer Research Center, Seattle, WA) Garnet Anderson, Ross Prentice, Andrea LaCroix, and Charles Kooperberg; Investigators and Academic Centers ‐ (Brigham and Women's Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson; (MedStar Health Research Institute/Howard University, Washington, DC) Barbara V. Howard; (Stanford Prevention Research Center, Stanford, CA) Marcia L. Stefanick; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Arizona, Tucson/Phoenix, AZ) Cynthia A. Thomson; (University at Buffalo, Buffalo, NY) Jean Wactawski‐Wende; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (Wake Forest University School of Medicine, Winston‐Salem, NC) Sally Shumaker; Women's Health Initiative Memory Study ‐ (Wake Forest University School of Medicine, Winston‐Salem, NC) Sally Shumaker. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. Funding Information: UCSF/UCSF2 (E.A.H., P.M.B, C.F.S.): The UCSF studies were supported by the NCI, National Institutes of Health, CA87014, CA1046282, CA122663 and CA154643, and R01CA87014, R01CA45614, R03CA14397, and R03CA150037 (E.A.H., P.M.B). The collection of cancer incidence data used in this study was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology, and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #1U58 DP000807‐01 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the authors, and endorsement by the State of California, the California Department of Health Services, the National Cancer Institute, or the Centers for Disease Control and Prevention or their contractors and subcontractors is not intended nor should be inferred. Funding Information: UTAH/Sheffield: National Institutes of Health CA134674. Partial support for data collection at the Utah site was made possible by the Utah Population Database (UPDB) and the Utah Cancer Registry (UCR). Partial support for all datasets within the UPDB is provided by the Huntsman Cancer Institute (HCI) and the HCI Cancer Center Support grant, P30 CA42014. The UCR is supported in part by NIH contract HHSN261201000026C from the National Cancer Institute SEER Program with additional support from the Utah State Department of Health and the University of Utah. Partial support for data collection in Sheffield, UK was made possible by funds from Yorkshire Cancer Research and the Sheffield Experimental Cancer Medicine Center. We thank the NCRI Haemato‐oncology Clinical Studies Group, colleagues in the North Trent Cancer Network the North Trent Haemato‐oncology Database. Funding Information: Hans‐Olov Adami is supported by the Karolinska Institutet Distinguished Professor Award (Dnr: 2368/10‐221). Funding Information: MCCS (G.G.G., G.S.): The Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian National Health and Medical Research Council grants 209057, 251553, 504711, 396414 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. The MCCS was made possible by the contribution of many people, including the original investigators, the teams that recruited the participants and continue working on follow‐up, and the many thousands of Melbourne residents who continue to participate in the study. Funding Information: Nicola Camp reports support from NIH R01CA134674. Partial support for data collection at the Utah site was made possible by the Utah Population Database (UPDB) and the Utah Cancer Registry (UCR). Partial support for all datasets within the UPDB is provided by the Huntsman Cancer Institute (HCI) and the HCI Comprehensive Cancer Center Support grant, P30 CA42014. The UCR is supported in part by NIH contract HHSN261201000026C from the National Cancer Institute SEER Program with additional support from the Utah State Department of Health and the University of Utah. Funding Information: James R Cerhan is supported by NIH grants R01 CA92153, R01 CA200703, P50 CA97274, U01 CA195568. Funding Information: IMSGC‐WTCCC2: The principal funding for this study was provided by the Wellcome Trust (085475/B/08/Z, 085475/Z/08/Z, 075491/Z/04/Z, and 068545/Z/02). The work was also supported by National Institutes of Health (AI076544, NS032830, NS049477, NS19142, NS049510, NS26799, NS43559, NS067305, CA104021, RR020092, RR024992 and K23N/S048869), US National Multiple Sclerosis Society (RG 4201‐A‐1), Nancy Davis Foundation, Cambridge NIHR Biomedical Research Center, UK Medical Research Council (G0700061, G0000934), Multiple Sclerosis Society of Great Britain and Northern Ireland (898/08), Wolfson Royal Society Merit Award, Peter Doherty fellowship, Lagrange Fellowship, Harry Weaver Neuroscience Scholarships, Australian National Health and Medical Research Council (NHMRC), Australian Research Council Linkage Program Grant, JHH Charitable Trust Fund, Multiple Sclerosis Research Australia, Health Research Council New Zealand, National MS Society of New Zealand, Wetenschappelijk Onderzoek Multiple Sclerose, Bayer Chair on Fundamental Genetic Research regarding the Neuroimmunological Aspects of Multiple Sclerosis, Biogen Idec Chair Translational Research in Multiple Sclerosis, FWO‐Vlaanderen, Belgian Neurological Society, Danish Multiple Sclerosis Society, Neuropromise EU grant (LSHM‐CT‐2005‐018637), Center of Excellence for Disease Genetics of the Academy of Finland, Sigrid Juselius Foundation, Helsinki University Central Hospital Research Foundation, Bundesministerium f{\"u}r Bildung und Technologie (KKNMS consortium Control MS), Deutsche Forschungsgemeinschaft, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (INSERM), Association pour la Recherche sur la Scl{\'e}rose En Plaques (ARSEP), Association Fran{\c c}aise contre les Myopathies (AFM), Italian Foundation for Multiple Sclerosis (FISM grants 2002/R/40, 2005/R/10, 2008/R/11, and 2008/R/15), Italian Ministry of Health (grant Giovani Ricercatori 2007 ‐ D.lgs 502/92), Regione Piemonte (grants 2003, 2004, 2008, 2009), CRT Foundation, Turin, Moorfields/UCL Institute of Ophthalmology NIHR Biomedical Research Center, Norwegian MS Register and Biobank, Research Council of Norway, South‐Eastern and Western Norway regional Health Authories, Ullev{\aa}l University Hospital Scientific Advisory Council, Haukeland University Hospital, Amici Centro Sclerosi Multipla del San Raffaele (ACESM), Association of British Neurologists, Spanish Ministry of Health (FISPI060117), Bibbi and Niels Jensens Foundation, Montel Williams foundation, Hj{\"a}rnfonden and Swedish medical research council (8691), Stockholm County Council (562183), Swedish Council for Working life and Social Research, Gemeinn{\"u}tzige Hertie Stiftung, Northern California Kaiser Permanente members and Polpharma Foundation, and Washington University Institute of Clinical and Translational Sciences—Brain, Behavioral and Performance Unit. We acknowledge use of data from the British 1958 Birth Cohort, the UK National Blood Service, the popgen biobank, the KORA and MONICA Augsburg studies, the Accelerated Cure Project, the Brigham & Women's Hospital PhenoGenetic Project, the Swedish CAD project, the Norwegian Bone Marrow Donor Registry, the Children's Hospital of Philadelphia (CHOP), the Swedish Breast Cancer study, BRC‐REFGENSEP (Piti{\'e}‐Salp{\^e}tri{\`e}re Center d'Investigation Clinique (CIC) and G{\'e}n{\'e}thon) and HYPERGENES (HEALTH‐F4‐2007‐201550). Projects received support from the German Ministry of Education and Research, the Helmholtz Zentrum M{\"u}nchen—National Research Center, the German National Genome Research Network (NGFN), the LMUinnovativ, the Knut and Alice Wallenberg Foundation, the Center for Applied Genomics from the Children's Hospital of Philadelphia Development Award, the Agency for Science & Technology and Research of Singapore, and the Susan G. Komen Breast Cancer Foundation. Funding Information: SLE: The Health and Retirement Study genetic data were obtained from dbGaP under accession phs000187.v1; the study is sponsored by the National Institute on Aging (grant numbers U01AG009740, RC2AG036495, and RC4AG039029) and was conducted by the University of Michigan. The melanoma study data were obtained from dbGaP under accession number phs000187.v1.p1. Research support to collect data and develop an application to support this project was provided by 3P50CA093459, 5P50CA097007, 5R01ES011740, and 5R01CA133996. Funding support for the Genes and Blood Clotting study was provided through the NIH/NHLBI (R37HL039693). The Genes and Blood Clotting Study is one of the Phase 3 studies as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with genotype cleaning was provided by the GENEVA Coordinating Center (U01 HG004446). Funding support for DNA extraction and genotyping, which was performed at the Broad Institute, was provided by NIH/NHLBI (R37HL039693). Additional support was provided by the Howard Hughes Medical Institute. The datasets used for the analyses described in this manuscript can be obtained from dbGaP at http://www.ncbi.nlm.nih.gov/sites/entrez?db=gap through dbGaP accession number phs000304.v1.p1. The CGEMS prostate cancer study data can be obtained from dbGaP under accession phs000207v1 Funding Information: PLCO: This research was supported by the Intramural Research Program of the National Cancer Institute and by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Funding Information: Pierre‐Antoine Gourraud is currently supported by the ATIP‐Avenir INSERM program and the Region Pays de Loire ConnecTalent, ARSEP Foundation (Fondation pour l'Aide {\`a} la recherche sur la Scl{\'e}rose En Plaques Foundation), the Nantes University Foundation, the PIA‐Investissmeent d'avenir RHU programme KTD Innov, and the H2020 EU‐TRAIN grant. Funding Information: All 92 authors agree that there are no conflicts of interest to report. Hans-Olov Adami is supported by the Karolinska Institutet Distinguished Professor Award (Dnr: 2368/10-221). Nicola Camp reports support from NIH R01CA134674. Partial support for data collection at the Utah site was made possible by the Utah Population Database (UPDB) and the Utah Cancer Registry (UCR). Partial support for all datasets within the UPDB is provided by the Huntsman Cancer Institute (HCI) and the HCI Comprehensive Cancer Center Support grant, P30 CA42014. Funding Information: GEC/Mayo GWAS: National Institutes of Health (CA118444, CA148690, CA92153). Intramural Research Program of the NIH, National Cancer Institute. Veterans Affairs Research Service. Data collection for Duke University was supported by a Leukemia & Lymphoma Society Career Development Award, the Bernstein Family Fund for Leukemia and Lymphoma Research, and the National Institutes of Health (K08CA134919), the National Center for Advancing Translational Science (UL1 TR000135). Funding Information: MCC‐Spain: The MCC‐Spain study is funded by the Instituto de Salud Carlos III (ISCIII – Spanish Government) (PI11/01810, PI14/01219, RCESP C03/09, and CIBERESP); the Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) – Generalitat de Catalunya (Catalonian Government) (2014SGR756). Nadia Garc{\'i}a and Marleny Vergara (ICO‐IDIBELL) provided technical support for this study. Funding Information: EPILYMPH: European Commission (grant references QLK4‐CT‐2000‐00422 and FOOD‐CT‐2006‐023103); Spanish Ministry of Economy and Competitiveness ‐ Carlos III Institute of Health cofunded by FEDER funds/European Regional Develpment Fund (ERDF) ‐ a way to build Europe (grants PI17/01280, PI14/01219, and CIBERESP) and Ag{\`e}ncia de Gesti{\'o} d'Ajuts Universitaris i de Recerca (AGAUR), CERCA Programme / Generalitat de Catalunya for institutional support (2017SGR1085) who had no role in the data collection, analysis or interpretation of the results; the NIH (contract NO1‐CO‐12400); the Compagnia di San Paolo—Programma Oncologia; the Federal Office for Radiation Protection grants StSch4261 and StSch4420, the Jos{\'e} Carreras Leukemia Foundation grant DJCLS‐R12/23, the German Federal Ministry for Education and Research (BMBF‐01‐EO‐1303); the Health Research Board, Ireland and Cancer Research Ireland; Czech Republic supported by MH CZ – DRO (MMCI, 00209805) and RECAMO, CZ.1.05/2.1.00/03.0101; Fondation de France and Association de Recherche Contre le Cancer. Funding Information: ELCCS (E.R.): The ECSG Lymphoma Case‐Control Study (ELCCS) were funded by Bloodwise and Leukemia & Lymphoma Research. Funding Information: Lenka Foretova is supported by a grant MH CZ ‐ DRO (MMCI, 00209805). Funding Information: Pierre‐Antoine Gourraud is currently supported by the ATIP‐Avenir INSERM program and the Region Pays de Loire ConnecTalent, ARSEP Foundation (Fondation pour l'Aide {\`a} la recherche sur la Scl{\'e}rose En Plaques Foundation”, the Nantes University Foundation, the PIA‐Investissmeent d'avenir RHU programme KTD Innov, and the H2020 EU‐TRAIN grant. Funding Information: Yolanda Benavente, Silvia de Sanjos{\'e} and Delphine Casabonne are supported by the Spanish Ministry of Economy and Competitiveness ‐ Carlos III Institute of Health cofunded by FEDER funds/European Regional Develpment Fund (ERDF) ‐ a way to build Europe (grant references CIBERESP); and the Ag{\`e}ncia de Gesti{\'o} d'Ajuts Universitaris i de Recerca (AGAUR), CERCA Programme/Generalitat de Catalunya for institutional support (2017SGR1085). Funding Information: MSKCC (K.O.): Geoffrey Beene Cancer Research Grant, Lymphoma Foundation (LF5541). Barbara K. Lipman Lymphoma Research Fund (74419). Robert and Kate Niehaus Clinical Cancer Genetics Research Initiative (57470), U01 HG007033. ENCODE, U01 HG007033 (J.V.). Funding Information: David Conti is supported by the following NIH grants: P01CA196569, R01CA201407, R01CA206019, and 5P30CA014089. Funding Information: SCALE (K.E.S., H.O.A., H.H.): Swedish Cancer Society (2009/659).Stockholm Country Council(20110229) and the Strategic Research Program in Epidemiology at Karolinska Institute. Danish Cancer Research Foundation Grant.Lundbeck Foundation Grant(R19‐A2364).Danish Cancer Society Grant(DP 08‐155). National Institutes of Health (5R01 CA69669‐02). Plan Denmark. Funding Information: Karin E Smedby is supported by the Strategic Research Program in Epidemiology at Karolinska Institute and National Institutes of Health (5R01 CA69669‐02). Funding Information: NCI‐SEER: Intramural Research Program of the National Cancer Institute, National Institutes of Health, and Public Health Service (N01‐PC‐65064, N01‐PC‐67008, N01‐PC‐ 67009, N01‐PC‐67010, N02‐PC‐71105). Publisher Copyright: {\textcopyright} 2019 Wiley Periodicals, Inc.",

year = "2019",

month = oct,

day = "1",

doi = "10.1002/gepi.22242",

language = "English (US)",

volume = "43",

pages = "844--863",

journal = "Genetic Epidemiology",

issn = "0741-0395",

publisher = "Wiley-Liss Inc.",

number = "7",

}

TY - JOUR

T1 - Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes

AU - Din, Lennox

AU - Sheikh, Mohammad

AU - Kosaraju, Nikitha

AU - Smedby, Karin Ekstrom

AU - Bernatsky, Sasha

AU - Berndt, Sonja I.

AU - Skibola, Christine F.

AU - Nieters, Alexandra

AU - Wang, Sophia

AU - McKay, James D.

AU - Cocco, Pierluigi

AU - Maynadié, Marc

AU - Foretová, Lenka

AU - Staines, Anthony

AU - Mack, Thomas M.

AU - de Sanjosé, Silvia

AU - Vyse, Timothy J.

AU - Padyukov, Leonid

AU - Monnereau, Alain

AU - Arslan, Alan A.

AU - Moore, Amy

AU - Brooks-Wilson, Angela R.

AU - Novak, Anne J.

AU - Glimelius, Bengt

AU - Birmann, Brenda M.

AU - Link, Brian K.

AU - Stewart, Carolyn

AU - Vajdic, Claire M.

AU - Haioun, Corinne

AU - Magnani, Corrado

AU - Conti, David V.

AU - Cox, David G.

AU - Casabonne, Delphine

AU - Albanes, Demetrius

AU - Kane, Eleanor

AU - Roman, Eve

AU - Muzi, Giacomo

AU - Salles, Gilles

AU - Giles, Graham G.

AU - Adami, Hans Olov

AU - Ghesquières, Hervé

AU - De Vivo, Immaculata

AU - Clavel, Jacqueline

AU - Cerhan, James R.

AU - Spinelli, John J.

AU - Hofmann, Jonathan

AU - Vijai, Joseph

AU - Curtin, Karen

AU - Costenbader, Karen H.

AU - Onel, Kenan

AU - Offit, Kenneth

AU - Teras, Lauren R.

AU - Morton, Lindsay

AU - Conde, Lucia

AU - Miligi, Lucia

AU - Melbye, Mads

AU - Ennas, Maria Grazia

AU - Liebow, Mark

AU - Purdue, Mark P.

AU - Glenn, Martha

AU - Southey, Melissa C.

AU - Din, Morris

AU - Rothman, Nathaniel

AU - Camp, Nicola J.

AU - Wong Doo, Nicole

AU - Becker, Nikolaus

AU - Pradhan, Nisha

AU - Bracci, Paige M.

AU - Boffetta, Paolo

AU - Vineis, Paolo

AU - Brennan, Paul

AU - Kraft, Peter

AU - Lan, Qing

AU - Severson, Richard K.

AU - Vermeulen, Roel C.H.

AU - Milne, Roger L.

AU - Kaaks, Rudolph

AU - Travis, Ruth C.

AU - Weinstein, Stephanie J.

AU - Chanock, Stephen J.

AU - Ansell, Stephen M.

AU - Slager, Susan L.

AU - Zheng, Tongzhang

AU - Zhang, Yawei

AU - Benavente, Yolanda

AU - Taub, Zachary

AU - Madireddy, Lohith

AU - Gourraud, Pierre Antoine

AU - Oksenberg, Jorge R.

AU - Cozen, Wendy

AU - Hjalgrim, Henrik

AU - Khankhanian, Pouya

N1 - Funding Information: WTCCC1: The principal funder of this project was the Wellcome Trust. Case collections were funded by: Arthritis Research Campaign, BDA Research, British Heart Foundation, British Hypertension Society, Diabetes UK, Glaxo‐Smith Kline Research and Development, Juvenile Diabetes Research Foundation, National Association for Colitis and Crohn's disease, SHERT (The Scottish Hospitals Endowment Research Trust), St Bartholomew's and The Royal London Charitable Foundation, UK Medical Research Council, UK NHS R&D and the Wellcome Trust. Statistical analyses were funded by a Commonwealth Scholarship, EU, EPSRC, Fundação para a Ciência e a Tecnologia (Portugal), National Institutes of Health, National Science Foundation and the Wellcome Trust. We acknowledge the many physicians, research fellows and research nurses who contributed to the various case collections, and the collection teams and senior management of the UK Blood Services responsible for the UK Blood Services Collection. For the 1958 Birth Cohort, venous blood collection was funded by the UK Medical Research Council and cell‐line production, DNA extraction, and processing by the Juvenile Diabetes Research Foundation and the Wellcome Trust. Funding Information: HPFS (Walter C. Willet): The HPFS was supported in part by National Institutes of Health grants CA167552, CA149445, and CA098122. We would like to thank the participants and staff of the Health Professionals Follow‐up Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. The study protocol was approved by the institutional review boards of the Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. Funding Information: CLL Meta‐Analysis: We thank I. Brock, K. Butterbach, A. Chabrier, D. Chan‐Lam, D. Connley, H. Cramp, R. Cutting, C. Dalley, H. Dykes, A. Gabbas, P. Gaddam, P. Hui, L. Irish, L. Jacobus, S. Kaul, L. Klareskog, A. Lai, J. Lunde, M. McAdams, D. Parisi, V. Rajamanickam, T. Rattle, L. Rigacci, R. Sargent, G. Specchia, M. Stagner, P. Taylor, C. Tornow, J. WiIliams and G. Wood. The overall GWAS project was supported by the intramural program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health. Funding Information: NSW NHL study (C.M.Vajdic): It was supported by grants from the Australian National Health and Medical Research Council (ID990920), the Cancer Council NSW, and the University of Sydney Faculty of Medicine. Funding Information: BC (J.S., A.B.W.): We thank R Gascoyne, J Connors, R Gallagher, T Lee, C Ng, Z Abanto, R Janoo‐Gilani, P Lee, S Leach. A Lai and her study staff, the members of the BC Cancer Agency Lymphoma Tumour Group, and all the participants of the study for making this research possible. The study was supported by grants from the Canadian Institutes for Health Research (CIHR); the Canadian Cancer Society; and the Michael Smith Foundation for Health Research. Funding Information: John J Spinelli is supported by the Canadian Institutes for Health Research (CIHR); the Canadian Cancer Society; and the Michael Smith Foundation for Health Research. Funding Information: Karen H. Costenbader is supported by NIH Grants R01 AR057327, and R01 AR049880. Funding Information: NHS (Meir J. Stampfer): The NHS was supported in part by National Institutes of Health grants CA186107, CA87969, CA49449, CA149445, CA098122, and CA134958. We would like to thank the participants and staff of the Nurses' Health Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. The study protocol was approved by the institutional review boards of the Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. Funding Information: NSFC: the National Natural Science Foundation of China (No. 61471078). Funding Information: WHI: WHI investigators are: Program Office—(National Heart, Lung, and Blood Institute, Bethesda, Maryland) Jacques Rossouw, Shari Ludlam, Dale Burwen, Joan McGowan, Leslie Ford, and Nancy Geller; Clinical Coordinating Center ‐ (Fred Hutchinson Cancer Research Center, Seattle, WA) Garnet Anderson, Ross Prentice, Andrea LaCroix, and Charles Kooperberg; Investigators and Academic Centers ‐ (Brigham and Women's Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson; (MedStar Health Research Institute/Howard University, Washington, DC) Barbara V. Howard; (Stanford Prevention Research Center, Stanford, CA) Marcia L. Stefanick; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Arizona, Tucson/Phoenix, AZ) Cynthia A. Thomson; (University at Buffalo, Buffalo, NY) Jean Wactawski‐Wende; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (Wake Forest University School of Medicine, Winston‐Salem, NC) Sally Shumaker; Women's Health Initiative Memory Study ‐ (Wake Forest University School of Medicine, Winston‐Salem, NC) Sally Shumaker. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. Funding Information: UCSF/UCSF2 (E.A.H., P.M.B, C.F.S.): The UCSF studies were supported by the NCI, National Institutes of Health, CA87014, CA1046282, CA122663 and CA154643, and R01CA87014, R01CA45614, R03CA14397, and R03CA150037 (E.A.H., P.M.B). The collection of cancer incidence data used in this study was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology, and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #1U58 DP000807‐01 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the authors, and endorsement by the State of California, the California Department of Health Services, the National Cancer Institute, or the Centers for Disease Control and Prevention or their contractors and subcontractors is not intended nor should be inferred. Funding Information: UTAH/Sheffield: National Institutes of Health CA134674. Partial support for data collection at the Utah site was made possible by the Utah Population Database (UPDB) and the Utah Cancer Registry (UCR). Partial support for all datasets within the UPDB is provided by the Huntsman Cancer Institute (HCI) and the HCI Cancer Center Support grant, P30 CA42014. The UCR is supported in part by NIH contract HHSN261201000026C from the National Cancer Institute SEER Program with additional support from the Utah State Department of Health and the University of Utah. Partial support for data collection in Sheffield, UK was made possible by funds from Yorkshire Cancer Research and the Sheffield Experimental Cancer Medicine Center. We thank the NCRI Haemato‐oncology Clinical Studies Group, colleagues in the North Trent Cancer Network the North Trent Haemato‐oncology Database. Funding Information: Hans‐Olov Adami is supported by the Karolinska Institutet Distinguished Professor Award (Dnr: 2368/10‐221). Funding Information: MCCS (G.G.G., G.S.): The Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian National Health and Medical Research Council grants 209057, 251553, 504711, 396414 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. The MCCS was made possible by the contribution of many people, including the original investigators, the teams that recruited the participants and continue working on follow‐up, and the many thousands of Melbourne residents who continue to participate in the study. Funding Information: Nicola Camp reports support from NIH R01CA134674. Partial support for data collection at the Utah site was made possible by the Utah Population Database (UPDB) and the Utah Cancer Registry (UCR). Partial support for all datasets within the UPDB is provided by the Huntsman Cancer Institute (HCI) and the HCI Comprehensive Cancer Center Support grant, P30 CA42014. The UCR is supported in part by NIH contract HHSN261201000026C from the National Cancer Institute SEER Program with additional support from the Utah State Department of Health and the University of Utah. Funding Information: James R Cerhan is supported by NIH grants R01 CA92153, R01 CA200703, P50 CA97274, U01 CA195568. Funding Information: IMSGC‐WTCCC2: The principal funding for this study was provided by the Wellcome Trust (085475/B/08/Z, 085475/Z/08/Z, 075491/Z/04/Z, and 068545/Z/02). The work was also supported by National Institutes of Health (AI076544, NS032830, NS049477, NS19142, NS049510, NS26799, NS43559, NS067305, CA104021, RR020092, RR024992 and K23N/S048869), US National Multiple Sclerosis Society (RG 4201‐A‐1), Nancy Davis Foundation, Cambridge NIHR Biomedical Research Center, UK Medical Research Council (G0700061, G0000934), Multiple Sclerosis Society of Great Britain and Northern Ireland (898/08), Wolfson Royal Society Merit Award, Peter Doherty fellowship, Lagrange Fellowship, Harry Weaver Neuroscience Scholarships, Australian National Health and Medical Research Council (NHMRC), Australian Research Council Linkage Program Grant, JHH Charitable Trust Fund, Multiple Sclerosis Research Australia, Health Research Council New Zealand, National MS Society of New Zealand, Wetenschappelijk Onderzoek Multiple Sclerose, Bayer Chair on Fundamental Genetic Research regarding the Neuroimmunological Aspects of Multiple Sclerosis, Biogen Idec Chair Translational Research in Multiple Sclerosis, FWO‐Vlaanderen, Belgian Neurological Society, Danish Multiple Sclerosis Society, Neuropromise EU grant (LSHM‐CT‐2005‐018637), Center of Excellence for Disease Genetics of the Academy of Finland, Sigrid Juselius Foundation, Helsinki University Central Hospital Research Foundation, Bundesministerium für Bildung und Technologie (KKNMS consortium Control MS), Deutsche Forschungsgemeinschaft, Institut National de la Santé et de la Recherche Médicale (INSERM), Association pour la Recherche sur la Sclérose En Plaques (ARSEP), Association Française contre les Myopathies (AFM), Italian Foundation for Multiple Sclerosis (FISM grants 2002/R/40, 2005/R/10, 2008/R/11, and 2008/R/15), Italian Ministry of Health (grant Giovani Ricercatori 2007 ‐ D.lgs 502/92), Regione Piemonte (grants 2003, 2004, 2008, 2009), CRT Foundation, Turin, Moorfields/UCL Institute of Ophthalmology NIHR Biomedical Research Center, Norwegian MS Register and Biobank, Research Council of Norway, South‐Eastern and Western Norway regional Health Authories, Ullevål University Hospital Scientific Advisory Council, Haukeland University Hospital, Amici Centro Sclerosi Multipla del San Raffaele (ACESM), Association of British Neurologists, Spanish Ministry of Health (FISPI060117), Bibbi and Niels Jensens Foundation, Montel Williams foundation, Hjärnfonden and Swedish medical research council (8691), Stockholm County Council (562183), Swedish Council for Working life and Social Research, Gemeinnützige Hertie Stiftung, Northern California Kaiser Permanente members and Polpharma Foundation, and Washington University Institute of Clinical and Translational Sciences—Brain, Behavioral and Performance Unit. We acknowledge use of data from the British 1958 Birth Cohort, the UK National Blood Service, the popgen biobank, the KORA and MONICA Augsburg studies, the Accelerated Cure Project, the Brigham & Women's Hospital PhenoGenetic Project, the Swedish CAD project, the Norwegian Bone Marrow Donor Registry, the Children's Hospital of Philadelphia (CHOP), the Swedish Breast Cancer study, BRC‐REFGENSEP (Pitié‐Salpêtrière Center d'Investigation Clinique (CIC) and Généthon) and HYPERGENES (HEALTH‐F4‐2007‐201550). Projects received support from the German Ministry of Education and Research, the Helmholtz Zentrum München—National Research Center, the German National Genome Research Network (NGFN), the LMUinnovativ, the Knut and Alice Wallenberg Foundation, the Center for Applied Genomics from the Children's Hospital of Philadelphia Development Award, the Agency for Science & Technology and Research of Singapore, and the Susan G. Komen Breast Cancer Foundation. Funding Information: SLE: The Health and Retirement Study genetic data were obtained from dbGaP under accession phs000187.v1; the study is sponsored by the National Institute on Aging (grant numbers U01AG009740, RC2AG036495, and RC4AG039029) and was conducted by the University of Michigan. The melanoma study data were obtained from dbGaP under accession number phs000187.v1.p1. Research support to collect data and develop an application to support this project was provided by 3P50CA093459, 5P50CA097007, 5R01ES011740, and 5R01CA133996. Funding support for the Genes and Blood Clotting study was provided through the NIH/NHLBI (R37HL039693). The Genes and Blood Clotting Study is one of the Phase 3 studies as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with genotype cleaning was provided by the GENEVA Coordinating Center (U01 HG004446). Funding support for DNA extraction and genotyping, which was performed at the Broad Institute, was provided by NIH/NHLBI (R37HL039693). Additional support was provided by the Howard Hughes Medical Institute. The datasets used for the analyses described in this manuscript can be obtained from dbGaP at http://www.ncbi.nlm.nih.gov/sites/entrez?db=gap through dbGaP accession number phs000304.v1.p1. The CGEMS prostate cancer study data can be obtained from dbGaP under accession phs000207v1 Funding Information: PLCO: This research was supported by the Intramural Research Program of the National Cancer Institute and by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Funding Information: Pierre‐Antoine Gourraud is currently supported by the ATIP‐Avenir INSERM program and the Region Pays de Loire ConnecTalent, ARSEP Foundation (Fondation pour l'Aide à la recherche sur la Sclérose En Plaques Foundation), the Nantes University Foundation, the PIA‐Investissmeent d'avenir RHU programme KTD Innov, and the H2020 EU‐TRAIN grant. Funding Information: All 92 authors agree that there are no conflicts of interest to report. Hans-Olov Adami is supported by the Karolinska Institutet Distinguished Professor Award (Dnr: 2368/10-221). Nicola Camp reports support from NIH R01CA134674. Partial support for data collection at the Utah site was made possible by the Utah Population Database (UPDB) and the Utah Cancer Registry (UCR). Partial support for all datasets within the UPDB is provided by the Huntsman Cancer Institute (HCI) and the HCI Comprehensive Cancer Center Support grant, P30 CA42014. Funding Information: GEC/Mayo GWAS: National Institutes of Health (CA118444, CA148690, CA92153). Intramural Research Program of the NIH, National Cancer Institute. Veterans Affairs Research Service. Data collection for Duke University was supported by a Leukemia & Lymphoma Society Career Development Award, the Bernstein Family Fund for Leukemia and Lymphoma Research, and the National Institutes of Health (K08CA134919), the National Center for Advancing Translational Science (UL1 TR000135). Funding Information: MCC‐Spain: The MCC‐Spain study is funded by the Instituto de Salud Carlos III (ISCIII – Spanish Government) (PI11/01810, PI14/01219, RCESP C03/09, and CIBERESP); the Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) – Generalitat de Catalunya (Catalonian Government) (2014SGR756). Nadia García and Marleny Vergara (ICO‐IDIBELL) provided technical support for this study. Funding Information: EPILYMPH: European Commission (grant references QLK4‐CT‐2000‐00422 and FOOD‐CT‐2006‐023103); Spanish Ministry of Economy and Competitiveness ‐ Carlos III Institute of Health cofunded by FEDER funds/European Regional Develpment Fund (ERDF) ‐ a way to build Europe (grants PI17/01280, PI14/01219, and CIBERESP) and Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR), CERCA Programme / Generalitat de Catalunya for institutional support (2017SGR1085) who had no role in the data collection, analysis or interpretation of the results; the NIH (contract NO1‐CO‐12400); the Compagnia di San Paolo—Programma Oncologia; the Federal Office for Radiation Protection grants StSch4261 and StSch4420, the José Carreras Leukemia Foundation grant DJCLS‐R12/23, the German Federal Ministry for Education and Research (BMBF‐01‐EO‐1303); the Health Research Board, Ireland and Cancer Research Ireland; Czech Republic supported by MH CZ – DRO (MMCI, 00209805) and RECAMO, CZ.1.05/2.1.00/03.0101; Fondation de France and Association de Recherche Contre le Cancer. Funding Information: ELCCS (E.R.): The ECSG Lymphoma Case‐Control Study (ELCCS) were funded by Bloodwise and Leukemia & Lymphoma Research. Funding Information: Lenka Foretova is supported by a grant MH CZ ‐ DRO (MMCI, 00209805). Funding Information: Pierre‐Antoine Gourraud is currently supported by the ATIP‐Avenir INSERM program and the Region Pays de Loire ConnecTalent, ARSEP Foundation (Fondation pour l'Aide à la recherche sur la Sclérose En Plaques Foundation”, the Nantes University Foundation, the PIA‐Investissmeent d'avenir RHU programme KTD Innov, and the H2020 EU‐TRAIN grant. Funding Information: Yolanda Benavente, Silvia de Sanjosé and Delphine Casabonne are supported by the Spanish Ministry of Economy and Competitiveness ‐ Carlos III Institute of Health cofunded by FEDER funds/European Regional Develpment Fund (ERDF) ‐ a way to build Europe (grant references CIBERESP); and the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR), CERCA Programme/Generalitat de Catalunya for institutional support (2017SGR1085). Funding Information: MSKCC (K.O.): Geoffrey Beene Cancer Research Grant, Lymphoma Foundation (LF5541). Barbara K. Lipman Lymphoma Research Fund (74419). Robert and Kate Niehaus Clinical Cancer Genetics Research Initiative (57470), U01 HG007033. ENCODE, U01 HG007033 (J.V.). Funding Information: David Conti is supported by the following NIH grants: P01CA196569, R01CA201407, R01CA206019, and 5P30CA014089. Funding Information: SCALE (K.E.S., H.O.A., H.H.): Swedish Cancer Society (2009/659).Stockholm Country Council(20110229) and the Strategic Research Program in Epidemiology at Karolinska Institute. Danish Cancer Research Foundation Grant.Lundbeck Foundation Grant(R19‐A2364).Danish Cancer Society Grant(DP 08‐155). National Institutes of Health (5R01 CA69669‐02). Plan Denmark. Funding Information: Karin E Smedby is supported by the Strategic Research Program in Epidemiology at Karolinska Institute and National Institutes of Health (5R01 CA69669‐02). Funding Information: NCI‐SEER: Intramural Research Program of the National Cancer Institute, National Institutes of Health, and Public Health Service (N01‐PC‐65064, N01‐PC‐67008, N01‐PC‐ 67009, N01‐PC‐67010, N02‐PC‐71105). Publisher Copyright: © 2019 Wiley Periodicals, Inc.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p =.0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

AB - Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p =.0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

KW - autoimmune disease

KW - genome-wide association study

KW - meta-analysis

KW - non-Hodgkin lymphoma

UR - http://www.scopus.com/inward/record.url?scp=85070768686&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070768686&partnerID=8YFLogxK

U2 - 10.1002/gepi.22242

DO - 10.1002/gepi.22242

M3 - Article

C2 - 31407831

AN - SCOPUS:85070768686

SN - 0741-0395

VL - 43

SP - 844

EP - 863

JO - Genetic Epidemiology

JF - Genetic Epidemiology

IS - 7

ER -

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes

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