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Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and...
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| Published in: | Nature communications 2016-03, Vol.7 (1), p.10933-9, Article 10933 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| creator | Berndt, Sonja I. Skibola, Christine F. Vijai, Joseph Wang, Zhaoming Kelly, Rachel S. Smedby, Karin E. Cozen, Wendy Wang, Sophia S. Lan, Qing Teras, Lauren R. Machado, Moara Yeager, Meredith Brooks-Wilson, Angela R. Hartge, Patricia Purdue, Mark P. Birmann, Brenda M. Vajdic, Claire M. Cocco, Pierluigi Zhang, Yawei Giles, Graham G. Zeleniuch-Jacquotte, Anne Lawrence, Charles Montalvan, Rebecca Hutchinson, Amy Ye, Yuanqing Call, Timothy G. Shanafelt, Tait D. Novak, Anne J. Kay, Neil E. Liebow, Mark Cunningham, Julie M. Allmer, Cristine Hjalgrim, Henrik Adami, Hans-Olov Melbye, Mads Glimelius, Bengt Chang, Ellen T. Glenn, Martha Curtin, Karen Cannon-Albright, Lisa A. Diver, W Ryan Weiner, George J. Conde, Lucia Bracci, Paige M. Riby, Jacques Arnett, Donna K. Leach, Justin M. Holly, Elizabeth A. Benavente, Yolanda Sala, Núria Casabonne, Delphine Becker, Nikolaus Brennan, Paul Foretova, Lenka Maynadie, Marc McKay, James Staines, Anthony Chaffee, Kari G. Achenbach, Sara J. Strom, Sara S. Leis, Jose F. Caporaso, Neil E. De Roos, Anneclaire J. Severson, Richard K. Kaaks, Rudolph Weiderpass, Elisabete Chirlaque, María- Dolores Vermeulen, Roel C. H. Travis, Ruth C. Southey, Melissa C. Milne, Roger L. Albanes, Demetrius Zheng, Tongzhang Holford, Theodore R. Maria, Ann Gascoyne, Randy D. Connors, Joseph M. Bertrand, Kimberly A. Giovannucci, Edward Kraft, Peter Kricker, Anne Turner, Jenny Ennas, Maria Grazia Miligi, Lucia Liang, Liming Ma, Baoshan Crouch, Simon Park, Ju-Hyun Chatterjee, Nilanjan North, Kari E. Snowden, John A. Wright, Josh Fraumeni, Joseph F. Offit, Kenneth Wu, Xifeng de Sanjose, Silvia Cerhan, James R. Chanock, Stephen J. Rothman, Nathaniel Slager, Susan L. |
| description | Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772,
EOMES
,
P
=2.55 × 10
−11
), 6p25.2 (rs73718779,
SERPINB6
,
P
=1.97 × 10
−8
) and 3q28 (rs9815073,
LPP
,
P
=3.62 × 10
−8
), as well as a new independent SNP at the known 2q13 locus (rs9308731,
BCL2L11
,
P
=1.00 × 10
−11
) in the combined analysis. We find suggestive evidence (
P |
| doi_str_mv | 10.1038/ncomms10933 |
| format | article |
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H. ; Travis, Ruth C. ; Southey, Melissa C. ; Milne, Roger L. ; Albanes, Demetrius ; Zheng, Tongzhang ; Holford, Theodore R. ; Maria, Ann ; Gascoyne, Randy D. ; Connors, Joseph M. ; Bertrand, Kimberly A. ; Giovannucci, Edward ; Kraft, Peter ; Kricker, Anne ; Turner, Jenny ; Ennas, Maria Grazia ; Miligi, Lucia ; Liang, Liming ; Ma, Baoshan ; Crouch, Simon ; Park, Ju-Hyun ; Chatterjee, Nilanjan ; North, Kari E. ; Snowden, John A. ; Wright, Josh ; Fraumeni, Joseph F. ; Offit, Kenneth ; Wu, Xifeng ; de Sanjose, Silvia ; Cerhan, James R. ; Chanock, Stephen J. ; Rothman, Nathaniel ; Slager, Susan L.</creator><creatorcontrib>Berndt, Sonja I. ; Skibola, Christine F. ; Vijai, Joseph ; Wang, Zhaoming ; Kelly, Rachel S. ; Smedby, Karin E. ; Cozen, Wendy ; Wang, Sophia S. ; Lan, Qing ; Teras, Lauren R. ; Machado, Moara ; Yeager, Meredith ; Brooks-Wilson, Angela R. ; Hartge, Patricia ; Purdue, Mark P. ; Birmann, Brenda M. ; Vajdic, Claire M. ; Cocco, Pierluigi ; Zhang, Yawei ; Giles, Graham G. ; Zeleniuch-Jacquotte, Anne ; Lawrence, Charles ; Montalvan, Rebecca ; Hutchinson, Amy ; Ye, Yuanqing ; Call, Timothy G. ; Shanafelt, Tait D. ; Novak, Anne J. ; Kay, Neil E. ; Liebow, Mark ; Cunningham, Julie M. ; Allmer, Cristine ; Hjalgrim, Henrik ; Adami, Hans-Olov ; Melbye, Mads ; Glimelius, Bengt ; Chang, Ellen T. ; Glenn, Martha ; Curtin, Karen ; Cannon-Albright, Lisa A. ; Diver, W Ryan ; Weiner, George J. ; Conde, Lucia ; Bracci, Paige M. ; Riby, Jacques ; Arnett, Donna K. ; Leach, Justin M. ; Holly, Elizabeth A. ; Benavente, Yolanda ; Sala, Núria ; Casabonne, Delphine ; Becker, Nikolaus ; Brennan, Paul ; Foretova, Lenka ; Maynadie, Marc ; McKay, James ; Staines, Anthony ; Chaffee, Kari G. ; Achenbach, Sara J. ; Strom, Sara S. ; Leis, Jose F. ; Caporaso, Neil E. ; De Roos, Anneclaire J. ; Severson, Richard K. ; Kaaks, Rudolph ; Weiderpass, Elisabete ; Chirlaque, María- Dolores ; Vermeulen, Roel C. H. ; Travis, Ruth C. ; Southey, Melissa C. ; Milne, Roger L. ; Albanes, Demetrius ; Zheng, Tongzhang ; Holford, Theodore R. ; Maria, Ann ; Gascoyne, Randy D. ; Connors, Joseph M. ; Bertrand, Kimberly A. ; Giovannucci, Edward ; Kraft, Peter ; Kricker, Anne ; Turner, Jenny ; Ennas, Maria Grazia ; Miligi, Lucia ; Liang, Liming ; Ma, Baoshan ; Crouch, Simon ; Park, Ju-Hyun ; Chatterjee, Nilanjan ; North, Kari E. ; Snowden, John A. ; Wright, Josh ; Fraumeni, Joseph F. ; Offit, Kenneth ; Wu, Xifeng ; de Sanjose, Silvia ; Cerhan, James R. ; Chanock, Stephen J. ; Rothman, Nathaniel ; Slager, Susan L.</creatorcontrib><description>Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772,
EOMES
,
P
=2.55 × 10
−11
), 6p25.2 (rs73718779,
SERPINB6
,
P
=1.97 × 10
−8
) and 3q28 (rs9815073,
LPP
,
P
=3.62 × 10
−8
), as well as a new independent SNP at the known 2q13 locus (rs9308731,
BCL2L11
,
P
=1.00 × 10
−11
) in the combined analysis. We find suggestive evidence (
P
<5 × 10
−7
) for two additional new loci at 4q24 (rs10028805,
BANK1
,
P
=7.19 × 10
−8
) and 3p22.2 (rs1274963,
CSRNP1
,
P
=2.12 × 10
−7
). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
Chronic lymphocytic leukemia is a highly inheritable cancer. Here the authors conduct a metaanalysis of four genome-wide association studies and identify three novel loci located near
EOMES
,
SERPINB6
and
LPP
associated with risk of this disease.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/ncomms10933</identifier><identifier>PMID: 26956414</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208/205/2138 ; 631/208/68 ; 631/67/1990/283/1895 ; 631/80/82/23 ; Adaptor Proteins, Signal Transducing - genetics ; Agent Orange ; Apoptosis ; Apoptosis Regulatory Proteins - genetics ; Bcl-2-Like Protein 11 ; Chromosome 2 ; Chromosome 3 ; Chromosome 4 ; Chronic lymphocytic leukemia ; Community medicine, Social medicine: 801 ; Genetic Predisposition to Disease ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Health sciences: 800 ; Helsefag: 800 ; Hematology ; Heritability ; Human health and pathology ; Humanities and Social Sciences ; Humans ; Leukemia ; Leukemia, Lymphocytic, Chronic, B-Cell - genetics ; Life Sciences ; Loci ; Lymphatic leukemia ; Malignancy ; Medical disciplines: 700 ; Medisinske Fag: 700 ; Membrane Proteins - genetics ; Meta-analysis ; multidisciplinary ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins - genetics ; Samfunnsmedisin, sosialmedisin: 801 ; Science ; Science (multidisciplinary) ; Serpins - genetics ; Single-nucleotide polymorphism ; T-Box Domain Proteins - genetics ; VDP ; White People - genetics</subject><ispartof>Nature communications, 2016-03, Vol.7 (1), p.10933-9, Article 10933</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Mar 2016</rights><rights>info:eu-repo/semantics/openAccess</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c645t-2e004fee65554222a650140297f28b561d52a89324af400b3aaa924e2049b8fe3</citedby><cites>FETCH-LOGICAL-c645t-2e004fee65554222a650140297f28b561d52a89324af400b3aaa924e2049b8fe3</cites><orcidid>0000-0001-9161-1357 ; 0000-0002-3612-8298 ; 0000-0002-7933-151X ; 0000-0002-8159-3025 ; 0000-0002-7313-1875 ; 0000-0002-5138-1099 ; 0000-0002-5546-8626 ; 0000-0003-3585-7613 ; 0000-0001-5230-0652 ; 0000-0003-4946-9099 ; 0000-0002-7874-3707 ; 0000-0002-4472-8103 ; 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Anthony</creatorcontrib><creatorcontrib>Chaffee, Kari G.</creatorcontrib><creatorcontrib>Achenbach, Sara J.</creatorcontrib><creatorcontrib>Strom, Sara S.</creatorcontrib><creatorcontrib>Leis, Jose F.</creatorcontrib><creatorcontrib>Caporaso, Neil E.</creatorcontrib><creatorcontrib>De Roos, Anneclaire J.</creatorcontrib><creatorcontrib>Severson, Richard K.</creatorcontrib><creatorcontrib>Kaaks, Rudolph</creatorcontrib><creatorcontrib>Weiderpass, Elisabete</creatorcontrib><creatorcontrib>Chirlaque, María- Dolores</creatorcontrib><creatorcontrib>Vermeulen, Roel C. H.</creatorcontrib><creatorcontrib>Travis, Ruth C.</creatorcontrib><creatorcontrib>Southey, Melissa C.</creatorcontrib><creatorcontrib>Milne, Roger L.</creatorcontrib><creatorcontrib>Albanes, Demetrius</creatorcontrib><creatorcontrib>Zheng, Tongzhang</creatorcontrib><creatorcontrib>Holford, Theodore R.</creatorcontrib><creatorcontrib>Maria, Ann</creatorcontrib><creatorcontrib>Gascoyne, Randy D.</creatorcontrib><creatorcontrib>Connors, Joseph M.</creatorcontrib><creatorcontrib>Bertrand, Kimberly A.</creatorcontrib><creatorcontrib>Giovannucci, Edward</creatorcontrib><creatorcontrib>Kraft, Peter</creatorcontrib><creatorcontrib>Kricker, Anne</creatorcontrib><creatorcontrib>Turner, Jenny</creatorcontrib><creatorcontrib>Ennas, Maria Grazia</creatorcontrib><creatorcontrib>Miligi, Lucia</creatorcontrib><creatorcontrib>Liang, Liming</creatorcontrib><creatorcontrib>Ma, Baoshan</creatorcontrib><creatorcontrib>Crouch, Simon</creatorcontrib><creatorcontrib>Park, Ju-Hyun</creatorcontrib><creatorcontrib>Chatterjee, Nilanjan</creatorcontrib><creatorcontrib>North, Kari E.</creatorcontrib><creatorcontrib>Snowden, John A.</creatorcontrib><creatorcontrib>Wright, Josh</creatorcontrib><creatorcontrib>Fraumeni, Joseph F.</creatorcontrib><creatorcontrib>Offit, Kenneth</creatorcontrib><creatorcontrib>Wu, Xifeng</creatorcontrib><creatorcontrib>de Sanjose, Silvia</creatorcontrib><creatorcontrib>Cerhan, James R.</creatorcontrib><creatorcontrib>Chanock, Stephen J.</creatorcontrib><creatorcontrib>Rothman, Nathaniel</creatorcontrib><creatorcontrib>Slager, Susan L.</creatorcontrib><title>Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772,
EOMES
,
P
=2.55 × 10
−11
), 6p25.2 (rs73718779,
SERPINB6
,
P
=1.97 × 10
−8
) and 3q28 (rs9815073,
LPP
,
P
=3.62 × 10
−8
), as well as a new independent SNP at the known 2q13 locus (rs9308731,
BCL2L11
,
P
=1.00 × 10
−11
) in the combined analysis. We find suggestive evidence (
P
<5 × 10
−7
) for two additional new loci at 4q24 (rs10028805,
BANK1
,
P
=7.19 × 10
−8
) and 3p22.2 (rs1274963,
CSRNP1
,
P
=2.12 × 10
−7
). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
Chronic lymphocytic leukemia is a highly inheritable cancer. Here the authors conduct a metaanalysis of four genome-wide association studies and identify three novel loci located near
EOMES
,
SERPINB6
and
LPP
associated with risk of this disease.</description><subject>631/208/205/2138</subject><subject>631/208/68</subject><subject>631/67/1990/283/1895</subject><subject>631/80/82/23</subject><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Agent Orange</subject><subject>Apoptosis</subject><subject>Apoptosis Regulatory Proteins - genetics</subject><subject>Bcl-2-Like Protein 11</subject><subject>Chromosome 2</subject><subject>Chromosome 3</subject><subject>Chromosome 4</subject><subject>Chronic lymphocytic leukemia</subject><subject>Community medicine, Social medicine: 801</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Health sciences: 800</subject><subject>Helsefag: 800</subject><subject>Hematology</subject><subject>Heritability</subject><subject>Human health and pathology</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</subject><subject>Life Sciences</subject><subject>Loci</subject><subject>Lymphatic leukemia</subject><subject>Malignancy</subject><subject>Medical disciplines: 700</subject><subject>Medisinske Fag: 700</subject><subject>Membrane Proteins - genetics</subject><subject>Meta-analysis</subject><subject>multidisciplinary</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Samfunnsmedisin, sosialmedisin: 801</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Serpins - genetics</subject><subject>Single-nucleotide polymorphism</subject><subject>T-Box Domain Proteins - genetics</subject><subject>VDP</subject><subject>White People - genetics</subject><issn>2041-1723</issn><issn>2041-1723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>3HK</sourceid><sourceid>DOA</sourceid><recordid>eNp1kstv1DAQxiMEolXpiTtE4gKCgJ-JfUFalUcrLeICXK3ZZLzrbRJv7aTV_vd4H612K_DBHo1__r6xPVn2kpKPlHD1qa9910VKNOdPslNGBC1oxfjTg_gkO49xSdLgmiohnmcnrNSyFFScZu4HDlBAD-06uph7m8-x9x0Wd67BHGL0tYPB-T6Pw9g4jHnjYu1vMcS8G9vBrVrM2wTl1oe8XgTfuzpv191q4ev1sIlxvMbOwYvsmYU24vl-Pct-f_v66-KymP78fnUxmRZ1KeRQMCREWMRSSikYY1BKQgVhurJMzWRJG8lAac4EWEHIjAOAZgLTdfVMWeRn2dVOt_GwNKvgOghr48GZbcKHuYGQCmvRME1tZcsyOaMgkmskICVUqG0NjdBJq9hpxTtcjbMjtX3qOkVoJCkrohL_4b_8F_dnsnUfR8MUU5wl_PMOT2yHTY39EKA9OnW807uFmftbIypVqoomgXc7gcWjY5eTqdnkCJWUJvJ2w77esXVwcXC96X0AQ1NXVGnmelPO2305wd-MGAfTpb_GtoUe_RgNrSpGRcm2F33zCF36MaQu2lJUyPQbJFHv7y19jAHtQ42UbDyVOWjfRL86fI0H9r5ZD143bfVzDAem_9D7C3gN-fA</recordid><startdate>20160309</startdate><enddate>20160309</enddate><creator>Berndt, Sonja I.</creator><creator>Skibola, Christine F.</creator><creator>Vijai, Joseph</creator><creator>Wang, Zhaoming</creator><creator>Kelly, Rachel S.</creator><creator>Smedby, Karin E.</creator><creator>Cozen, Wendy</creator><creator>Wang, Sophia S.</creator><creator>Lan, Qing</creator><creator>Teras, Lauren R.</creator><creator>Machado, Moara</creator><creator>Yeager, Meredith</creator><creator>Brooks-Wilson, Angela R.</creator><creator>Hartge, Patricia</creator><creator>Purdue, Mark P.</creator><creator>Birmann, Brenda M.</creator><creator>Vajdic, Claire M.</creator><creator>Cocco, Pierluigi</creator><creator>Zhang, Yawei</creator><creator>Giles, Graham G.</creator><creator>Zeleniuch-Jacquotte, Anne</creator><creator>Lawrence, Charles</creator><creator>Montalvan, Rebecca</creator><creator>Hutchinson, Amy</creator><creator>Ye, Yuanqing</creator><creator>Call, Timothy G.</creator><creator>Shanafelt, Tait D.</creator><creator>Novak, Anne J.</creator><creator>Kay, Neil E.</creator><creator>Liebow, Mark</creator><creator>Cunningham, Julie M.</creator><creator>Allmer, Cristine</creator><creator>Hjalgrim, Henrik</creator><creator>Adami, Hans-Olov</creator><creator>Melbye, Mads</creator><creator>Glimelius, Bengt</creator><creator>Chang, Ellen T.</creator><creator>Glenn, Martha</creator><creator>Curtin, Karen</creator><creator>Cannon-Albright, Lisa A.</creator><creator>Diver, W Ryan</creator><creator>Weiner, George J.</creator><creator>Conde, Lucia</creator><creator>Bracci, Paige M.</creator><creator>Riby, Jacques</creator><creator>Arnett, Donna K.</creator><creator>Leach, Justin M.</creator><creator>Holly, Elizabeth A.</creator><creator>Benavente, Yolanda</creator><creator>Sala, Núria</creator><creator>Casabonne, Delphine</creator><creator>Becker, Nikolaus</creator><creator>Brennan, Paul</creator><creator>Foretova, Lenka</creator><creator>Maynadie, Marc</creator><creator>McKay, James</creator><creator>Staines, Anthony</creator><creator>Chaffee, Kari G.</creator><creator>Achenbach, Sara J.</creator><creator>Strom, Sara S.</creator><creator>Leis, Jose F.</creator><creator>Caporaso, Neil E.</creator><creator>De Roos, Anneclaire J.</creator><creator>Severson, Richard K.</creator><creator>Kaaks, Rudolph</creator><creator>Weiderpass, Elisabete</creator><creator>Chirlaque, María- Dolores</creator><creator>Vermeulen, Roel C. 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H. ; Travis, Ruth C. ; Southey, Melissa C. ; Milne, Roger L. ; Albanes, Demetrius ; Zheng, Tongzhang ; Holford, Theodore R. ; Maria, Ann ; Gascoyne, Randy D. ; Connors, Joseph M. ; Bertrand, Kimberly A. ; Giovannucci, Edward ; Kraft, Peter ; Kricker, Anne ; Turner, Jenny ; Ennas, Maria Grazia ; Miligi, Lucia ; Liang, Liming ; Ma, Baoshan ; Crouch, Simon ; Park, Ju-Hyun ; Chatterjee, Nilanjan ; North, Kari E. ; Snowden, John A. ; Wright, Josh ; Fraumeni, Joseph F. ; Offit, Kenneth ; Wu, Xifeng ; de Sanjose, Silvia ; Cerhan, James R. ; Chanock, Stephen J. ; Rothman, Nathaniel ; Slager, Susan L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c645t-2e004fee65554222a650140297f28b561d52a89324af400b3aaa924e2049b8fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>631/208/205/2138</topic><topic>631/208/68</topic><topic>631/67/1990/283/1895</topic><topic>631/80/82/23</topic><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Agent Orange</topic><topic>Apoptosis</topic><topic>Apoptosis Regulatory Proteins - genetics</topic><topic>Bcl-2-Like Protein 11</topic><topic>Chromosome 2</topic><topic>Chromosome 3</topic><topic>Chromosome 4</topic><topic>Chronic lymphocytic leukemia</topic><topic>Community medicine, Social medicine: 801</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Health sciences: 800</topic><topic>Helsefag: 800</topic><topic>Hematology</topic><topic>Heritability</topic><topic>Human health and pathology</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Leukemia</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</topic><topic>Life Sciences</topic><topic>Loci</topic><topic>Lymphatic leukemia</topic><topic>Malignancy</topic><topic>Medical disciplines: 700</topic><topic>Medisinske Fag: 700</topic><topic>Membrane Proteins - genetics</topic><topic>Meta-analysis</topic><topic>multidisciplinary</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Samfunnsmedisin, sosialmedisin: 801</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Serpins - genetics</topic><topic>Single-nucleotide polymorphism</topic><topic>T-Box Domain Proteins - genetics</topic><topic>VDP</topic><topic>White People - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Berndt, Sonja I.</creatorcontrib><creatorcontrib>Skibola, Christine F.</creatorcontrib><creatorcontrib>Vijai, Joseph</creatorcontrib><creatorcontrib>Wang, Zhaoming</creatorcontrib><creatorcontrib>Kelly, Rachel S.</creatorcontrib><creatorcontrib>Smedby, Karin E.</creatorcontrib><creatorcontrib>Cozen, Wendy</creatorcontrib><creatorcontrib>Wang, Sophia S.</creatorcontrib><creatorcontrib>Lan, Qing</creatorcontrib><creatorcontrib>Teras, Lauren R.</creatorcontrib><creatorcontrib>Machado, Moara</creatorcontrib><creatorcontrib>Yeager, Meredith</creatorcontrib><creatorcontrib>Brooks-Wilson, Angela R.</creatorcontrib><creatorcontrib>Hartge, Patricia</creatorcontrib><creatorcontrib>Purdue, Mark P.</creatorcontrib><creatorcontrib>Birmann, Brenda M.</creatorcontrib><creatorcontrib>Vajdic, Claire M.</creatorcontrib><creatorcontrib>Cocco, Pierluigi</creatorcontrib><creatorcontrib>Zhang, Yawei</creatorcontrib><creatorcontrib>Giles, Graham G.</creatorcontrib><creatorcontrib>Zeleniuch-Jacquotte, Anne</creatorcontrib><creatorcontrib>Lawrence, Charles</creatorcontrib><creatorcontrib>Montalvan, Rebecca</creatorcontrib><creatorcontrib>Hutchinson, Amy</creatorcontrib><creatorcontrib>Ye, Yuanqing</creatorcontrib><creatorcontrib>Call, Timothy G.</creatorcontrib><creatorcontrib>Shanafelt, Tait D.</creatorcontrib><creatorcontrib>Novak, Anne J.</creatorcontrib><creatorcontrib>Kay, Neil E.</creatorcontrib><creatorcontrib>Liebow, Mark</creatorcontrib><creatorcontrib>Cunningham, Julie M.</creatorcontrib><creatorcontrib>Allmer, Cristine</creatorcontrib><creatorcontrib>Hjalgrim, Henrik</creatorcontrib><creatorcontrib>Adami, Hans-Olov</creatorcontrib><creatorcontrib>Melbye, Mads</creatorcontrib><creatorcontrib>Glimelius, Bengt</creatorcontrib><creatorcontrib>Chang, Ellen T.</creatorcontrib><creatorcontrib>Glenn, Martha</creatorcontrib><creatorcontrib>Curtin, Karen</creatorcontrib><creatorcontrib>Cannon-Albright, Lisa A.</creatorcontrib><creatorcontrib>Diver, W Ryan</creatorcontrib><creatorcontrib>Weiner, George J.</creatorcontrib><creatorcontrib>Conde, Lucia</creatorcontrib><creatorcontrib>Bracci, Paige M.</creatorcontrib><creatorcontrib>Riby, Jacques</creatorcontrib><creatorcontrib>Arnett, Donna K.</creatorcontrib><creatorcontrib>Leach, Justin M.</creatorcontrib><creatorcontrib>Holly, Elizabeth A.</creatorcontrib><creatorcontrib>Benavente, Yolanda</creatorcontrib><creatorcontrib>Sala, Núria</creatorcontrib><creatorcontrib>Casabonne, Delphine</creatorcontrib><creatorcontrib>Becker, Nikolaus</creatorcontrib><creatorcontrib>Brennan, Paul</creatorcontrib><creatorcontrib>Foretova, Lenka</creatorcontrib><creatorcontrib>Maynadie, Marc</creatorcontrib><creatorcontrib>McKay, James</creatorcontrib><creatorcontrib>Staines, Anthony</creatorcontrib><creatorcontrib>Chaffee, Kari G.</creatorcontrib><creatorcontrib>Achenbach, Sara J.</creatorcontrib><creatorcontrib>Strom, Sara S.</creatorcontrib><creatorcontrib>Leis, Jose F.</creatorcontrib><creatorcontrib>Caporaso, Neil E.</creatorcontrib><creatorcontrib>De Roos, Anneclaire J.</creatorcontrib><creatorcontrib>Severson, Richard K.</creatorcontrib><creatorcontrib>Kaaks, Rudolph</creatorcontrib><creatorcontrib>Weiderpass, Elisabete</creatorcontrib><creatorcontrib>Chirlaque, María- Dolores</creatorcontrib><creatorcontrib>Vermeulen, Roel C. 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Abstracts</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><collection>NORA - Norwegian Open Research Archives</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SWEPUB Uppsala universitet full text</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SWEPUB Uppsala universitet</collection><collection>SwePub Articles full text</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Nature communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Berndt, Sonja I.</au><au>Skibola, Christine F.</au><au>Vijai, Joseph</au><au>Wang, Zhaoming</au><au>Kelly, Rachel S.</au><au>Smedby, Karin E.</au><au>Cozen, Wendy</au><au>Wang, Sophia S.</au><au>Lan, Qing</au><au>Teras, Lauren R.</au><au>Machado, Moara</au><au>Yeager, Meredith</au><au>Brooks-Wilson, Angela R.</au><au>Hartge, Patricia</au><au>Purdue, Mark P.</au><au>Birmann, Brenda M.</au><au>Vajdic, Claire M.</au><au>Cocco, Pierluigi</au><au>Zhang, Yawei</au><au>Giles, Graham G.</au><au>Zeleniuch-Jacquotte, Anne</au><au>Lawrence, Charles</au><au>Montalvan, Rebecca</au><au>Hutchinson, Amy</au><au>Ye, Yuanqing</au><au>Call, Timothy G.</au><au>Shanafelt, Tait D.</au><au>Novak, Anne J.</au><au>Kay, Neil E.</au><au>Liebow, Mark</au><au>Cunningham, Julie M.</au><au>Allmer, Cristine</au><au>Hjalgrim, Henrik</au><au>Adami, Hans-Olov</au><au>Melbye, Mads</au><au>Glimelius, Bengt</au><au>Chang, Ellen T.</au><au>Glenn, Martha</au><au>Curtin, Karen</au><au>Cannon-Albright, Lisa A.</au><au>Diver, W Ryan</au><au>Weiner, George J.</au><au>Conde, Lucia</au><au>Bracci, Paige M.</au><au>Riby, Jacques</au><au>Arnett, Donna K.</au><au>Leach, Justin M.</au><au>Holly, Elizabeth A.</au><au>Benavente, Yolanda</au><au>Sala, Núria</au><au>Casabonne, Delphine</au><au>Becker, Nikolaus</au><au>Brennan, Paul</au><au>Foretova, Lenka</au><au>Maynadie, Marc</au><au>McKay, James</au><au>Staines, Anthony</au><au>Chaffee, Kari G.</au><au>Achenbach, Sara J.</au><au>Strom, Sara S.</au><au>Leis, Jose F.</au><au>Caporaso, Neil E.</au><au>De Roos, Anneclaire J.</au><au>Severson, Richard K.</au><au>Kaaks, Rudolph</au><au>Weiderpass, Elisabete</au><au>Chirlaque, María- Dolores</au><au>Vermeulen, Roel C. H.</au><au>Travis, Ruth C.</au><au>Southey, Melissa C.</au><au>Milne, Roger L.</au><au>Albanes, Demetrius</au><au>Zheng, Tongzhang</au><au>Holford, Theodore R.</au><au>Maria, Ann</au><au>Gascoyne, Randy D.</au><au>Connors, Joseph M.</au><au>Bertrand, Kimberly A.</au><au>Giovannucci, Edward</au><au>Kraft, Peter</au><au>Kricker, Anne</au><au>Turner, Jenny</au><au>Ennas, Maria Grazia</au><au>Miligi, Lucia</au><au>Liang, Liming</au><au>Ma, Baoshan</au><au>Crouch, Simon</au><au>Park, Ju-Hyun</au><au>Chatterjee, Nilanjan</au><au>North, Kari E.</au><au>Snowden, John A.</au><au>Wright, Josh</au><au>Fraumeni, Joseph F.</au><au>Offit, Kenneth</au><au>Wu, Xifeng</au><au>de Sanjose, Silvia</au><au>Cerhan, James R.</au><au>Chanock, Stephen J.</au><au>Rothman, Nathaniel</au><au>Slager, Susan L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia</atitle><jtitle>Nature communications</jtitle><stitle>Nat Commun</stitle><addtitle>Nat Commun</addtitle><date>2016-03-09</date><risdate>2016</risdate><volume>7</volume><issue>1</issue><spage>10933</spage><epage>9</epage><pages>10933-9</pages><artnum>10933</artnum><issn>2041-1723</issn><eissn>2041-1723</eissn><abstract>Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772,
EOMES
,
P
=2.55 × 10
−11
), 6p25.2 (rs73718779,
SERPINB6
,
P
=1.97 × 10
−8
) and 3q28 (rs9815073,
LPP
,
P
=3.62 × 10
−8
), as well as a new independent SNP at the known 2q13 locus (rs9308731,
BCL2L11
,
P
=1.00 × 10
−11
) in the combined analysis. We find suggestive evidence (
P
<5 × 10
−7
) for two additional new loci at 4q24 (rs10028805,
BANK1
,
P
=7.19 × 10
−8
) and 3p22.2 (rs1274963,
CSRNP1
,
P
=2.12 × 10
−7
). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
Chronic lymphocytic leukemia is a highly inheritable cancer. Here the authors conduct a metaanalysis of four genome-wide association studies and identify three novel loci located near
EOMES
,
SERPINB6
and
LPP
associated with risk of this disease.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26956414</pmid><doi>10.1038/ncomms10933</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9161-1357</orcidid><orcidid>https://orcid.org/0000-0002-3612-8298</orcidid><orcidid>https://orcid.org/0000-0002-7933-151X</orcidid><orcidid>https://orcid.org/0000-0002-8159-3025</orcidid><orcidid>https://orcid.org/0000-0002-7313-1875</orcidid><orcidid>https://orcid.org/0000-0002-5138-1099</orcidid><orcidid>https://orcid.org/0000-0002-5546-8626</orcidid><orcidid>https://orcid.org/0000-0003-3585-7613</orcidid><orcidid>https://orcid.org/0000-0001-5230-0652</orcidid><orcidid>https://orcid.org/0000-0003-4946-9099</orcidid><orcidid>https://orcid.org/0000-0002-7874-3707</orcidid><orcidid>https://orcid.org/0000-0002-4472-8103</orcidid><orcidid>https://orcid.org/0000-0001-6795-6080</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-1723 |
| ispartof | Nature communications, 2016-03, Vol.7 (1), p.10933-9, Article 10933 |
| issn | 2041-1723 2041-1723 |
| language | eng |
| recordid | cdi_doaj_primary_oai_doaj_org_article_291f7f66c64e40539e0a55a7e9fcad49 |
| source | Nature_系列刊; NORA - Norwegian Open Research Archives; Publicly Available Content (ProQuest); PubMed Central; Springer Nature - nature.com Journals - Fully Open Access |
| subjects | 631/208/205/2138 631/208/68 631/67/1990/283/1895 631/80/82/23 Adaptor Proteins, Signal Transducing - genetics Agent Orange Apoptosis Apoptosis Regulatory Proteins - genetics Bcl-2-Like Protein 11 Chromosome 2 Chromosome 3 Chromosome 4 Chronic lymphocytic leukemia Community medicine, Social medicine: 801 Genetic Predisposition to Disease Genome-wide association studies Genome-Wide Association Study Genomes Health sciences: 800 Helsefag: 800 Hematology Heritability Human health and pathology Humanities and Social Sciences Humans Leukemia Leukemia, Lymphocytic, Chronic, B-Cell - genetics Life Sciences Loci Lymphatic leukemia Malignancy Medical disciplines: 700 Medisinske Fag: 700 Membrane Proteins - genetics Meta-analysis multidisciplinary Polymorphism, Single Nucleotide Proto-Oncogene Proteins - genetics Samfunnsmedisin, sosialmedisin: 801 Science Science (multidisciplinary) Serpins - genetics Single-nucleotide polymorphism T-Box Domain Proteins - genetics VDP White People - genetics |
| title | Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia |
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