Genome-wide association study of glioma and meta-analysis

Preetha Rajaraman, Beatrice S. Melin, Zhaoming Wang, Roberta McKean-Cowdin, Dominique S. Michaud, Sophia S. Wang, Melissa Bondy, Richard Houlston, Robert B. Jenkins, Margaret Wrensch, Meredith Yeager, Anders Ahlbom, Demetrius Albanes, Ulrika Andersson, Laura E Beane Freeman, Julie E. Buring, Mary Ann Butler, Melissa Braganza, Tania Carreon, Maria Feychting & 50 others Sarah J. Fleming, Susan M. Gapstur, J. Michael Gaziano, Graham G. Giles, Goran Hallmans, Roger Henriksson, Judith Hoffman-Bolton, Peter D. Inskip, Christoffer Johansen, Cari M. Kitahara, Mark Lathrop, Chenwei Liu, Loic Le Marchand, Martha S. Linet, Stefan Lonn, Ulrike Peters, Mark P. Purdue, Nathaniel Rothman, Avima M. Ruder, Marc Sanson, Howard D. Sesso, Gianluca Severi, Gianluca Shu, Matthias Simon, Meir Stampfer, Victoria L. Stevens, Kala Visvanathan, Emily White, Alicja Wolk, Anne Zeleniuch-Jacquotte, Wei Zheng, Paul Decker, Victor Enciso-Mora, Brooke Fridley, Yu Tang Gao, Matthew Kosel, Daniel H. Lachance, Ching Lau, Terri Rice, Anthony Swerdlow, Joseph L. Wiemels, John K. Wiencke, Sanjay Shete, Yong Bing Xiang, Yuanyuan Xiao, Robert N. Hoover, Joseph F. Fraumeni, Nilanjan Chatterjee, Patricia Hartge, Stephen J. Chanock

Research output: Contribution to journalArticle

Abstract

Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.

Original languageEnglish (US)
Pages (from-to)1877-1888
Number of pages12
JournalHuman Genetics
Volume131
Issue number12
DOIs
StatePublished - Dec 2012

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Genome-Wide Association Study
Glioma
Meta-Analysis
Cohort Studies
Case-Control Studies
Neoplasms
Brain Neoplasms
Single Nucleotide Polymorphism
Genome
Population

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Rajaraman, P., Melin, B. S., Wang, Z., McKean-Cowdin, R., Michaud, D. S., Wang, S. S., ... Chanock, S. J. (2012). Genome-wide association study of glioma and meta-analysis. Human Genetics, 131(12), 1877-1888. https://doi.org/10.1007/s00439-012-1212-0

Genome-wide association study of glioma and meta-analysis. / Rajaraman, Preetha; Melin, Beatrice S.; Wang, Zhaoming; McKean-Cowdin, Roberta; Michaud, Dominique S.; Wang, Sophia S.; Bondy, Melissa; Houlston, Richard; Jenkins, Robert B.; Wrensch, Margaret; Yeager, Meredith; Ahlbom, Anders; Albanes, Demetrius; Andersson, Ulrika; Freeman, Laura E Beane; Buring, Julie E.; Butler, Mary Ann; Braganza, Melissa; Carreon, Tania; Feychting, Maria; Fleming, Sarah J.; Gapstur, Susan M.; Gaziano, J. Michael; Giles, Graham G.; Hallmans, Goran; Henriksson, Roger; Hoffman-Bolton, Judith; Inskip, Peter D.; Johansen, Christoffer; Kitahara, Cari M.; Lathrop, Mark; Liu, Chenwei; Marchand, Loic Le; Linet, Martha S.; Lonn, Stefan; Peters, Ulrike; Purdue, Mark P.; Rothman, Nathaniel; Ruder, Avima M.; Sanson, Marc; Sesso, Howard D.; Severi, Gianluca; Shu, Gianluca; Simon, Matthias; Stampfer, Meir; Stevens, Victoria L.; Visvanathan, Kala; White, Emily; Wolk, Alicja; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Decker, Paul; Enciso-Mora, Victor; Fridley, Brooke; Gao, Yu Tang; Kosel, Matthew; Lachance, Daniel H.; Lau, Ching; Rice, Terri; Swerdlow, Anthony; Wiemels, Joseph L.; Wiencke, John K.; Shete, Sanjay; Xiang, Yong Bing; Xiao, Yuanyuan; Hoover, Robert N.; Fraumeni, Joseph F.; Chatterjee, Nilanjan; Hartge, Patricia; Chanock, Stephen J.

In: Human Genetics, Vol. 131, No. 12, 12.2012, p. 1877-1888.

Research output: Contribution to journalArticle

Rajaraman, P, Melin, BS, Wang, Z, McKean-Cowdin, R, Michaud, DS, Wang, SS, Bondy, M, Houlston, R, Jenkins, RB, Wrensch, M, Yeager, M, Ahlbom, A, Albanes, D, Andersson, U, Freeman, LEB, Buring, JE, Butler, MA, Braganza, M, Carreon, T, Feychting, M, Fleming, SJ, Gapstur, SM, Gaziano, JM, Giles, GG, Hallmans, G, Henriksson, R, Hoffman-Bolton, J, Inskip, PD, Johansen, C, Kitahara, CM, Lathrop, M, Liu, C, Marchand, LL, Linet, MS, Lonn, S, Peters, U, Purdue, MP, Rothman, N, Ruder, AM, Sanson, M, Sesso, HD, Severi, G, Shu, G, Simon, M, Stampfer, M, Stevens, VL, Visvanathan, K, White, E, Wolk, A, Zeleniuch-Jacquotte, A, Zheng, W, Decker, P, Enciso-Mora, V, Fridley, B, Gao, YT, Kosel, M, Lachance, DH, Lau, C, Rice, T, Swerdlow, A, Wiemels, JL, Wiencke, JK, Shete, S, Xiang, YB, Xiao, Y, Hoover, RN, Fraumeni, JF, Chatterjee, N, Hartge, P & Chanock, SJ 2012, 'Genome-wide association study of glioma and meta-analysis', Human Genetics, vol. 131, no. 12, pp. 1877-1888. https://doi.org/10.1007/s00439-012-1212-0
Rajaraman P, Melin BS, Wang Z, McKean-Cowdin R, Michaud DS, Wang SS et al. Genome-wide association study of glioma and meta-analysis. Human Genetics. 2012 Dec;131(12):1877-1888. https://doi.org/10.1007/s00439-012-1212-0
Rajaraman, Preetha ; Melin, Beatrice S. ; Wang, Zhaoming ; McKean-Cowdin, Roberta ; Michaud, Dominique S. ; Wang, Sophia S. ; Bondy, Melissa ; Houlston, Richard ; Jenkins, Robert B. ; Wrensch, Margaret ; Yeager, Meredith ; Ahlbom, Anders ; Albanes, Demetrius ; Andersson, Ulrika ; Freeman, Laura E Beane ; Buring, Julie E. ; Butler, Mary Ann ; Braganza, Melissa ; Carreon, Tania ; Feychting, Maria ; Fleming, Sarah J. ; Gapstur, Susan M. ; Gaziano, J. Michael ; Giles, Graham G. ; Hallmans, Goran ; Henriksson, Roger ; Hoffman-Bolton, Judith ; Inskip, Peter D. ; Johansen, Christoffer ; Kitahara, Cari M. ; Lathrop, Mark ; Liu, Chenwei ; Marchand, Loic Le ; Linet, Martha S. ; Lonn, Stefan ; Peters, Ulrike ; Purdue, Mark P. ; Rothman, Nathaniel ; Ruder, Avima M. ; Sanson, Marc ; Sesso, Howard D. ; Severi, Gianluca ; Shu, Gianluca ; Simon, Matthias ; Stampfer, Meir ; Stevens, Victoria L. ; Visvanathan, Kala ; White, Emily ; Wolk, Alicja ; Zeleniuch-Jacquotte, Anne ; Zheng, Wei ; Decker, Paul ; Enciso-Mora, Victor ; Fridley, Brooke ; Gao, Yu Tang ; Kosel, Matthew ; Lachance, Daniel H. ; Lau, Ching ; Rice, Terri ; Swerdlow, Anthony ; Wiemels, Joseph L. ; Wiencke, John K. ; Shete, Sanjay ; Xiang, Yong Bing ; Xiao, Yuanyuan ; Hoover, Robert N. ; Fraumeni, Joseph F. ; Chatterjee, Nilanjan ; Hartge, Patricia ; Chanock, Stephen J. / Genome-wide association study of glioma and meta-analysis. In: Human Genetics. 2012 ; Vol. 131, No. 12. pp. 1877-1888.
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T1 - Genome-wide association study of glioma and meta-analysis

AU - Rajaraman, Preetha

AU - Melin, Beatrice S.

AU - Wang, Zhaoming

AU - McKean-Cowdin, Roberta

AU - Michaud, Dominique S.

AU - Wang, Sophia S.

AU - Bondy, Melissa

AU - Houlston, Richard

AU - Jenkins, Robert B.

AU - Wrensch, Margaret

AU - Yeager, Meredith

AU - Ahlbom, Anders

AU - Albanes, Demetrius

AU - Andersson, Ulrika

AU - Freeman, Laura E Beane

AU - Buring, Julie E.

AU - Butler, Mary Ann

AU - Braganza, Melissa

AU - Carreon, Tania

AU - Feychting, Maria

AU - Fleming, Sarah J.

AU - Gapstur, Susan M.

AU - Gaziano, J. Michael

AU - Giles, Graham G.

AU - Hallmans, Goran

AU - Henriksson, Roger

AU - Hoffman-Bolton, Judith

AU - Inskip, Peter D.

AU - Johansen, Christoffer

AU - Kitahara, Cari M.

AU - Lathrop, Mark

AU - Liu, Chenwei

AU - Marchand, Loic Le

AU - Linet, Martha S.

AU - Lonn, Stefan

AU - Peters, Ulrike

AU - Purdue, Mark P.

AU - Rothman, Nathaniel

AU - Ruder, Avima M.

AU - Sanson, Marc

AU - Sesso, Howard D.

AU - Severi, Gianluca

AU - Shu, Gianluca

AU - Simon, Matthias

AU - Stampfer, Meir

AU - Stevens, Victoria L.

AU - Visvanathan, Kala

AU - White, Emily

AU - Wolk, Alicja

AU - Zeleniuch-Jacquotte, Anne

AU - Zheng, Wei

AU - Decker, Paul

AU - Enciso-Mora, Victor

AU - Fridley, Brooke

AU - Gao, Yu Tang

AU - Kosel, Matthew

AU - Lachance, Daniel H.

AU - Lau, Ching

AU - Rice, Terri

AU - Swerdlow, Anthony

AU - Wiemels, Joseph L.

AU - Wiencke, John K.

AU - Shete, Sanjay

AU - Xiang, Yong Bing

AU - Xiao, Yuanyuan

AU - Hoover, Robert N.

AU - Fraumeni, Joseph F.

AU - Chatterjee, Nilanjan

AU - Hartge, Patricia

AU - Chanock, Stephen J.

PY - 2012/12

Y1 - 2012/12

N2 - Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.

AB - Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.

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