Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32

Lucia Conde, Eran Halperin, Nicholas K Akers, Kevin M Brown, Karin E Smedby, Nathaniel Rothman, Alexandra Nieters, Susan L Slager, Angela Brooks-Wilson, Luz Agana, Jacques Riby, Jianjun Liu, Hans-Olov Adami, Hatef Darabi, Henrik Hjalgrim, Hui-Qi Low, Keith Humphreys, Mads Melbye, Ellen T Chang, Bengt Glimelius, Wendy Cozen, Scott Davis, Patricia Hartge, Lindsay M Morton, Maryjean Schenk, Sophia S Wang, Bruce Armstrong, Anne Kricker, Sam Milliken, Mark P Purdue, Claire M Vajdic, Peter Boyle, Qing Lan, Shelia H Zahm, Yawei Zhang, Tongzhang Zheng, Nikolaus Becker, Yolanda Benavente, Paolo Boffetta, Paul Brennan, Katja Butterbach, Pierluigi Cocco, Lenka Foretova, Marc Maynadié, Silvia de Sanjosé, Anthony Staines, John J Spinelli, Sara J Achenbach, Timothy G Call, Nicola J Camp, Martha Glenn, Neil E Caporaso, James R Cerhan, Julie M Cunningham, Lynn R Goldin, Curtis A Hanson, Neil E Kay, Mark C Lanasa, Jose F Leis, Gerald E Marti, Kari G Rabe, Laura Z Rassenti, Logan G Spector, Sara S Strom, Celine M Vachon, J Brice Weinberg, Elizabeth A Holly, Stephen Chanock, Martyn T Smith, Paige M Bracci, Christine F Skibola, Lucia Conde, Eran Halperin, Nicholas K Akers, Kevin M Brown, Karin E Smedby, Nathaniel Rothman, Alexandra Nieters, Susan L Slager, Angela Brooks-Wilson, Luz Agana, Jacques Riby, Jianjun Liu, Hans-Olov Adami, Hatef Darabi, Henrik Hjalgrim, Hui-Qi Low, Keith Humphreys, Mads Melbye, Ellen T Chang, Bengt Glimelius, Wendy Cozen, Scott Davis, Patricia Hartge, Lindsay M Morton, Maryjean Schenk, Sophia S Wang, Bruce Armstrong, Anne Kricker, Sam Milliken, Mark P Purdue, Claire M Vajdic, Peter Boyle, Qing Lan, Shelia H Zahm, Yawei Zhang, Tongzhang Zheng, Nikolaus Becker, Yolanda Benavente, Paolo Boffetta, Paul Brennan, Katja Butterbach, Pierluigi Cocco, Lenka Foretova, Marc Maynadié, Silvia de Sanjosé, Anthony Staines, John J Spinelli, Sara J Achenbach, Timothy G Call, Nicola J Camp, Martha Glenn, Neil E Caporaso, James R Cerhan, Julie M Cunningham, Lynn R Goldin, Curtis A Hanson, Neil E Kay, Mark C Lanasa, Jose F Leis, Gerald E Marti, Kari G Rabe, Laura Z Rassenti, Logan G Spector, Sara S Strom, Celine M Vachon, J Brice Weinberg, Elizabeth A Holly, Stephen Chanock, Martyn T Smith, Paige M Bracci, Christine F Skibola

Abstract

To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).

Figures

Figure 1. LD and association results for…
Figure 1. LD and association results for the FL-associated regions in the major histocompatibility complex (MHC)
In the main panel, trend p-values (as -log10) are shown for SNPs genotyped in the MHC region between positions 30,000Mb and 35,000Mb, where two independent FL-associated peaks were found. The first peak, represented by rs6457327 (in yellow), is located at 6p21.33 in the MHC Class I region. The second independent peak, represented by rs10484561 (in green), is located at 6p21.32 in the MHC Class II region. The secondary panel shows the SNPs genotyped (in black) and imputed (in red) in Stage 1 in a 500kb region centered on rs10484561 at 6p21.32. Imputations were based on data from HapMap Phase II release #22 in CEU population. Figure constructed using the snp.plotter R package (http://cbdb.nimh.nih.gov/∼kristin/snp.plotter.html).

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Source: PubMed

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