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1.  A genome-wide association study of Hodgkin Lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21, and 10p14 (GATA3) 
Nature genetics  2010;42(12):1126-1130.
To identify predisposition loci for classical Hodgkin Lymphoma (cHL) we conducted a genome-wide association study of 589 cHL cases and 5,199 controls with validation in 4 independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL; odds ratio [OR]=1.22, Pcombined=1.91×10−8), 8q24.21 (rs2019960, PVT1; OR=1.33, Pcombined=1.26×10−13) and 10p14 (rs501764, GATA3; OR=1.25, Pcombined=7.05×10−8). Furthermore, we confirmed the role of the MHC in disease etiology by revealing a strong HLA association (rs6903608; OR=1.70, Pcombined=2.84×10−50). These data provide new insight into the pathogenesis of cHL.
doi:10.1038/ng.696
PMCID: PMC4268499  PMID: 21037568
2.  Polymorphism in the Interleukin-7 Receptor-alpha and Outcome after Allogeneic Hematopoietic Cell Transplantation with Matched Unrelated Donor 
Interleukin-7 (IL-7) is essential for T cell development in the thymus and maintenance of peripheral T cells. The α-chain of the IL-7R is polymorphic with the existence of SNPs that give rise to nonsynonymous amino acid substitutions. We previously found an association between donor genotypes and increased treatment related mortality (TRM) (rs1494555G) and acute graft versus host disease (aGvHD) (rs1494555G and rs1494558T) after hematopoietic cell transplantation (HCT). Some studies have confirmed an association between rs6897932C and multiple sclerosis. In the present study we evaluated the prognostic significance of IL-7Rα SNP genotypes in 590-recipient/donor pairs that received HLA matched unrelated donor HCT for hematological malignancies. Consistent with the primary studies, the rs1494555GG and rs1494558TT genotypes of the donor were associated with aGvHD and chronic GvHD in the univariate analysis. The T allele of rs6897932 was suggestive of an association with increased frequency of relapse by univariate analysis (p=0.017) and multivariate analysis (p=0.015). In conclusion, this study provides further evidence of a role of the IL-7 pathway and IL-7Rα SNPs in HCT.
doi:10.1111/sji.12077
PMCID: PMC3982186  PMID: 23692589
3.  GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32 and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell Lymphoma 
PLoS Genetics  2011;7(4):e1001378.
Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL–associated locus on 6p21.32, rs2647012 (ORcombined = 0.64, Pcombined = 2×10−21) located 962 bp away from rs10484561 (r2<0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012:ORadjusted = 0.70, Padjusted = 4×10−12; rs10484561:ORadjusted = 1.64, Padjusted = 5×10−15). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL–associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (ORcombined = 1.36, Pcombined = 1.4×10−7). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL.
Author Summary
Earlier studies have established a marker rs10484561, in the HLA class II region on 6p21.32, associated with increased follicular lymphoma (FL) risk. Here, in a three-stage genome-wide association study of 1,428 FL cases and 6,581 controls, we identified a second independent FL–associated marker on 6p21.32, rs2647012, located 962 bp away from rs10484561. The associations at two SNPs remained genome-wide significant after mutual adjustment. Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct lineage from that of rs10484561 and tags a novel allele with an opposite, protective effect on FL risk. Moreover, in an analysis of the top 6 FL–associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma. Our results reveal the presence of allelic heterogeneity at 6p21.32 in FL risk and suggest a shared genetic etiology with the common diffuse large B-cell lymphoma subtype.
doi:10.1371/journal.pgen.1001378
PMCID: PMC3080853  PMID: 21533074

Results 1-3 (3)