Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region

Christine F Skibola; Sonja I Berndt; Joseph Vijai; Lucia Conde; Zhaoming Wang; Meredith Yeager; Paul I W de Bakker; Brenda M Birmann; Claire M Vajdic; Jia-Nee Foo; Paige M Bracci; Roel C H Vermeulen; Susan L Slager; Silvia de Sanjose; Sophia S Wang; Martha S Linet; Gilles Salles; Qing Lan; Gianluca Severi; Henrik Hjalgrim; Tracy Lightfoot; Mads Melbye; Jian Gu; Hervé Ghesquières; Brian K Link; Lindsay M Morton; Elizabeth A Holly; Alexandra Gwen Smith; Lesley F Tinker; Lauren R Teras; Anne Kricker; Nikolaus Becker; Mark P Purdue; John J Spinelli; Yawei Zhang; Graham G Giles; Paolo Vineis; Alain Monnereau; Kimberly A Bertrand; Demetrius Albanes; Anne Zeleniuch-Jacquotte; Attilio Gabbas; Charles C Chung; Laurie Burdett; Amy Hutchinson; Charles Lawrence; Rebecca Montalvan; Liming Liang; Jinyan Huang; Baoshan Ma; Jianjun Liu; Hans-Olov Adami; Bengt Glimelius; Yuanqing Ye; Grzegorz S Nowakowski; Ahmet Dogan; Carrie A Thompson; Thomas M Habermann; Anne J Novak; Mark Liebow; Thomas E Witzig; George J Weiner; Maryjean Schenk; Patricia Hartge; Anneclaire J De Roos; Wendy Cozen; Degui Zhi; Nicholas K Akers; Jacques Riby; Martyn T Smith; Mortimer Lacher; Danylo J Villano; Ann Maria; Eve Roman; Eleanor Kane; Rebecca D Jackson; Kari E North; W Ryan Diver; Jenny Turner; Bruce K Armstrong; Yolanda Benavente; Paolo Boffetta; Paul Brennan; Lenka Foretova; Marc Maynadie; Anthony Staines; James McKay; Angela R Brooks-Wilson; Tongzhang Zheng; Theodore R Holford; Saioa Chamosa; Rudolph Kaaks; Rachel S Kelly; Bodil Ohlsson; Ruth C Travis; Elisabete Weiderpass; Jacqueline Clavel; Edward Giovannucci; Peter Kraft; Jarmo Virtamo; Patrizio Mazza; Pierluigi Cocco; Maria Grazia Ennas; Brian C H Chiu; Joseph F Fraumeni; Alexandra Nieters; Kenneth Offit; Xifeng Wu; James R Cerhan; Karin E Smedby; Stephen J Chanock; Nathaniel Rothman

doi:10.1016/j.ajhg.2014.09.004

Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region

Christine F Skibola, Sonja I Berndt, Joseph Vijai, Lucia Conde, Zhaoming Wang, Meredith Yeager, Paul I W de Bakker, Brenda M Birmann, Claire M Vajdic, Jia-Nee Foo, Paige M Bracci, Roel C H Vermeulen, Susan L Slager, Silvia de Sanjose, Sophia S Wang, Martha S Linet, Gilles Salles, Qing Lan, Gianluca Severi, Henrik HjalgrimTracy Lightfoot, Mads Melbye, Jian Gu, Hervé Ghesquières, Brian K Link, Lindsay M Morton, Elizabeth A Holly, Alexandra Gwen Smith, Lesley F Tinker, Lauren R Teras, Anne Kricker, Nikolaus Becker, Mark P Purdue, John J Spinelli, Yawei Zhang, Graham G Giles, Paolo Vineis, Alain Monnereau, Kimberly A Bertrand, Demetrius Albanes, Anne Zeleniuch-Jacquotte, Attilio Gabbas, Charles C Chung, Laurie Burdett, Amy Hutchinson, Charles Lawrence, Rebecca Montalvan, Liming Liang, Jinyan Huang, Baoshan Ma, Jianjun Liu, Hans-Olov Adami, Bengt Glimelius, Yuanqing Ye, Grzegorz S Nowakowski, Ahmet Dogan, Carrie A Thompson, Thomas M Habermann, Anne J Novak, Mark Liebow, Thomas E Witzig, George J Weiner, Maryjean Schenk, Patricia Hartge, Anneclaire J De Roos, Wendy Cozen, Degui Zhi, Nicholas K Akers, Jacques Riby, Martyn T Smith, Mortimer Lacher, Danylo J Villano, Ann Maria, Eve Roman, Eleanor Kane, Rebecca D Jackson, Kari E North, W Ryan Diver, Jenny Turner, Bruce K Armstrong, Yolanda Benavente, Paolo Boffetta, Paul Brennan, Lenka Foretova, Marc Maynadie, Anthony Staines, James McKay, Angela R Brooks-Wilson, Tongzhang Zheng, Theodore R Holford, Saioa Chamosa, Rudolph Kaaks, Rachel S Kelly, Bodil Ohlsson, Ruth C Travis, Elisabete Weiderpass, Jacqueline Clavel, Edward Giovannucci, Peter Kraft, Jarmo Virtamo, Patrizio Mazza, Pierluigi Cocco, Maria Grazia Ennas, Brian C H Chiu, Joseph F Fraumeni, Alexandra Nieters, Kenneth Offit, Xifeng Wu, James R Cerhan, Karin E Smedby, Stephen J Chanock, Nathaniel Rothman

Health Sciences

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

Abstract

Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.

Original language	English
Pages (from-to)	462-471
Number of pages	10
Journal	American journal of human genetics
Volume	95
Issue number	4
DOIs	https://doi.org/10.1016/j.ajhg.2014.09.004
Publication status	Published - 2 Oct 2014

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Skibola, C. F., Berndt, S. I., Vijai, J., Conde, L., Wang, Z., Yeager, M., de Bakker, P. I. W., Birmann, B. M., Vajdic, C. M., Foo, J.-N., Bracci, P. M., Vermeulen, R. C. H., Slager, S. L., de Sanjose, S., Wang, S. S., Linet, M. S., Salles, G., Lan, Q., Severi, G., ... Rothman, N. (2014). Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region. American journal of human genetics, 95(4), 462-471. https://doi.org/10.1016/j.ajhg.2014.09.004

@article{06ee4f83ab9d4d5e9edd8ba6f7278a8d,

title = "Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region",

abstract = "Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.",

author = "Skibola, {Christine F} and Berndt, {Sonja I} and Joseph Vijai and Lucia Conde and Zhaoming Wang and Meredith Yeager and {de Bakker}, {Paul I W} and Birmann, {Brenda M} and Vajdic, {Claire M} and Jia-Nee Foo and Bracci, {Paige M} and Vermeulen, {Roel C H} and Slager, {Susan L} and {de Sanjose}, Silvia and Wang, {Sophia S} and Linet, {Martha S} and Gilles Salles and Qing Lan and Gianluca Severi and Henrik Hjalgrim and Tracy Lightfoot and Mads Melbye and Jian Gu and Herv{\'e} Ghesqui{\`e}res and Link, {Brian K} and Morton, {Lindsay M} and Holly, {Elizabeth A} and Smith, {Alexandra Gwen} and Tinker, {Lesley F} and Teras, {Lauren R} and Anne Kricker and Nikolaus Becker and Purdue, {Mark P} and Spinelli, {John J} and Yawei Zhang and Giles, {Graham G} and Paolo Vineis and Alain Monnereau and Bertrand, {Kimberly A} and Demetrius Albanes and Anne Zeleniuch-Jacquotte and Attilio Gabbas and Chung, {Charles C} and Laurie Burdett and Amy Hutchinson and Charles Lawrence and Rebecca Montalvan and Liming Liang and Jinyan Huang and Baoshan Ma and Jianjun Liu and Hans-Olov Adami and Bengt Glimelius and Yuanqing Ye and Nowakowski, {Grzegorz S} and Ahmet Dogan and Thompson, {Carrie A} and Habermann, {Thomas M} and Novak, {Anne J} and Mark Liebow and Witzig, {Thomas E} and Weiner, {George J} and Maryjean Schenk and Patricia Hartge and {De Roos}, {Anneclaire J} and Wendy Cozen and Degui Zhi and Akers, {Nicholas K} and Jacques Riby and Smith, {Martyn T} and Mortimer Lacher and Villano, {Danylo J} and Ann Maria and Eve Roman and Eleanor Kane and Jackson, {Rebecca D} and North, {Kari E} and Diver, {W Ryan} and Jenny Turner and Armstrong, {Bruce K} and Yolanda Benavente and Paolo Boffetta and Paul Brennan and Lenka Foretova and Marc Maynadie and Anthony Staines and James McKay and Brooks-Wilson, {Angela R} and Tongzhang Zheng and Holford, {Theodore R} and Saioa Chamosa and Rudolph Kaaks and Kelly, {Rachel S} and Bodil Ohlsson and Travis, {Ruth C} and Elisabete Weiderpass and Jacqueline Clavel and Edward Giovannucci and Peter Kraft and Jarmo Virtamo and Patrizio Mazza and Pierluigi Cocco and Ennas, {Maria Grazia} and Chiu, {Brian C H} and Fraumeni, {Joseph F} and Alexandra Nieters and Kenneth Offit and Xifeng Wu and Cerhan, {James R} and Smedby, {Karin E} and Chanock, {Stephen J} and Nathaniel Rothman",

year = "2014",

month = oct,

day = "2",

doi = "10.1016/j.ajhg.2014.09.004",

language = "English",

volume = "95",

pages = "462--471",

journal = "American journal of human genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "4",

}

Skibola, CF, Berndt, SI, Vijai, J, Conde, L, Wang, Z, Yeager, M, de Bakker, PIW, Birmann, BM, Vajdic, CM, Foo, J-N, Bracci, PM, Vermeulen, RCH, Slager, SL, de Sanjose, S, Wang, SS, Linet, MS, Salles, G, Lan, Q, Severi, G, Hjalgrim, H, Lightfoot, T, Melbye, M, Gu, J, Ghesquières, H, Link, BK, Morton, LM, Holly, EA, Smith, AG, Tinker, LF, Teras, LR, Kricker, A, Becker, N, Purdue, MP, Spinelli, JJ, Zhang, Y, Giles, GG, Vineis, P, Monnereau, A, Bertrand, KA, Albanes, D, Zeleniuch-Jacquotte, A, Gabbas, A, Chung, CC, Burdett, L, Hutchinson, A, Lawrence, C, Montalvan, R, Liang, L, Huang, J, Ma, B, Liu, J, Adami, H-O, Glimelius, B, Ye, Y, Nowakowski, GS, Dogan, A, Thompson, CA, Habermann, TM, Novak, AJ, Liebow, M, Witzig, TE, Weiner, GJ, Schenk, M, Hartge, P, De Roos, AJ, Cozen, W, Zhi, D, Akers, NK, Riby, J, Smith, MT, Lacher, M, Villano, DJ, Maria, A, Roman, E , Kane, E, Jackson, RD, North, KE, Diver, WR, Turner, J, Armstrong, BK, Benavente, Y, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, Staines, A, McKay, J, Brooks-Wilson, AR, Zheng, T, Holford, TR, Chamosa, S, Kaaks, R, Kelly, RS, Ohlsson, B, Travis, RC, Weiderpass, E, Clavel, J, Giovannucci, E, Kraft, P, Virtamo, J, Mazza, P, Cocco, P, Ennas, MG, Chiu, BCH, Fraumeni, JF, Nieters, A, Offit, K, Wu, X, Cerhan, JR, Smedby, KE, Chanock, SJ & Rothman, N 2014, 'Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region', American journal of human genetics, vol. 95, no. 4, pp. 462-471. https://doi.org/10.1016/j.ajhg.2014.09.004

TY - JOUR

T1 - Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region

AU - Skibola, Christine F

AU - Berndt, Sonja I

AU - Vijai, Joseph

AU - Conde, Lucia

AU - Wang, Zhaoming

AU - Yeager, Meredith

AU - de Bakker, Paul I W

AU - Birmann, Brenda M

AU - Vajdic, Claire M

AU - Foo, Jia-Nee

AU - Bracci, Paige M

AU - Vermeulen, Roel C H

AU - Slager, Susan L

AU - de Sanjose, Silvia

AU - Wang, Sophia S

AU - Linet, Martha S

AU - Salles, Gilles

AU - Lan, Qing

AU - Severi, Gianluca

AU - Hjalgrim, Henrik

AU - Lightfoot, Tracy

AU - Melbye, Mads

AU - Gu, Jian

AU - Ghesquières, Hervé

AU - Link, Brian K

AU - Morton, Lindsay M

AU - Holly, Elizabeth A

AU - Smith, Alexandra Gwen

AU - Tinker, Lesley F

AU - Teras, Lauren R

AU - Kricker, Anne

AU - Becker, Nikolaus

AU - Purdue, Mark P

AU - Spinelli, John J

AU - Zhang, Yawei

AU - Giles, Graham G

AU - Vineis, Paolo

AU - Monnereau, Alain

AU - Bertrand, Kimberly A

AU - Albanes, Demetrius

AU - Zeleniuch-Jacquotte, Anne

AU - Gabbas, Attilio

AU - Chung, Charles C

AU - Burdett, Laurie

AU - Hutchinson, Amy

AU - Lawrence, Charles

AU - Montalvan, Rebecca

AU - Liang, Liming

AU - Huang, Jinyan

AU - Ma, Baoshan

AU - Liu, Jianjun

AU - Adami, Hans-Olov

AU - Glimelius, Bengt

AU - Ye, Yuanqing

AU - Nowakowski, Grzegorz S

AU - Dogan, Ahmet

AU - Thompson, Carrie A

AU - Habermann, Thomas M

AU - Novak, Anne J

AU - Liebow, Mark

AU - Witzig, Thomas E

AU - Weiner, George J

AU - Schenk, Maryjean

AU - Hartge, Patricia

AU - De Roos, Anneclaire J

AU - Cozen, Wendy

AU - Zhi, Degui

AU - Akers, Nicholas K

AU - Riby, Jacques

AU - Smith, Martyn T

AU - Lacher, Mortimer

AU - Villano, Danylo J

AU - Maria, Ann

AU - Roman, Eve

AU - Kane, Eleanor

AU - Jackson, Rebecca D

AU - North, Kari E

AU - Diver, W Ryan

AU - Turner, Jenny

AU - Armstrong, Bruce K

AU - Benavente, Yolanda

AU - Boffetta, Paolo

AU - Brennan, Paul

AU - Foretova, Lenka

AU - Maynadie, Marc

AU - Staines, Anthony

AU - McKay, James

AU - Brooks-Wilson, Angela R

AU - Zheng, Tongzhang

AU - Holford, Theodore R

AU - Chamosa, Saioa

AU - Kaaks, Rudolph

AU - Kelly, Rachel S

AU - Ohlsson, Bodil

AU - Travis, Ruth C

AU - Weiderpass, Elisabete

AU - Clavel, Jacqueline

AU - Giovannucci, Edward

AU - Kraft, Peter

AU - Virtamo, Jarmo

AU - Mazza, Patrizio

AU - Cocco, Pierluigi

AU - Ennas, Maria Grazia

AU - Chiu, Brian C H

AU - Fraumeni, Joseph F

AU - Nieters, Alexandra

AU - Offit, Kenneth

AU - Wu, Xifeng

AU - Cerhan, James R

AU - Smedby, Karin E

AU - Chanock, Stephen J

AU - Rothman, Nathaniel

PY - 2014/10/2

Y1 - 2014/10/2

N2 - Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.

AB - Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.

U2 - 10.1016/j.ajhg.2014.09.004

DO - 10.1016/j.ajhg.2014.09.004

M3 - Article

C2 - 25279986

SN - 0002-9297

VL - 95

SP - 462

EP - 471

JO - American journal of human genetics

JF - American journal of human genetics

IS - 4

ER -