Table 2.

Integration of expression quantitative trait loci, histone modification, promoter capture Hi-C data at non-HLA Hodgkin lymphoma risk loci to identify candidate causal genes at Hodgkin lymphoma risk loci

LocusSentinel SNPPosition, (bp, hg19)Gene(s) in LD blockCoding variant(s)Promotor/UTR variant(s)Expression quantitative trait loci in LCLsExpression quantitative trait loci in T cellH3K27Ac histone peak*Hi-C contact(s) in naive or total B cellsHi-C contact(s) in T cellsHi-C contact(s) in HRS cellEvidence of perturbation in HLCandidate biological mechanism
2p16.1 rs2420518 61054980      Naive B cell REL REL  REL84  Constitutive NF-κB activation (REL)72, Altered B-cell differentiation and germinal center reaction (REL)50  
3p24.1 rs3806624 27764623 EOMES  EOMES, (3′-UTR)  EOMES (↑) (CD8+) Effector memory CD8+ T cell, plasma cell, L-428 AZI2, CMC1, NEK10, OXSM, NGLY1, ZCWPW2 EOMES, AZI2, CMC1, NEK10, OXSM, NGLY1, ZCWPW2 AZI2, CMC1, EOMES85, Exhausted CD8 T-cell phenotype (EOMES)61,81,82, Constitutive NF-κB activation (AZI2),73  
3q28 rs4459895 187954414 LPP     CD38− naive B cell, naive B cell, germinal center B cell, L-428    BCL686  Dysfunction of B-cell germinal center reaction (BCL6, mir-28),51,52  
5q31.1 rs848 131996500 IL-13 (p.Gln144Arg) IL-13, (3′-UTR)   L-428    IL-1387  Altered CD4+ T-cell function (IL-13)62  
6p21.31 rs649775 33684313 ITPR3, UQCC2, IP6K3  IP6K3, (3′-UTR) ITPR3 (↓)  CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, naive B cell, class-switched memory B cell BAK1, SYNGAP1, GGNBP1, LINC00336 BAK1, GRM4, SYNGAP1, KIFC1, CUTA, PHF1, GGNBP1, LINC003336   Altered B-cell differentiation (ITPR3),88  
6q22.33 rs9482849 128288536 PTPRK     CD4+ T cell, central memory CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, L-428 PTPRK, THEMIS   PTPRK89  Altered T-cell differentiation (PTPRK, THEMIS),63,64  
6q23.3 rs9402684 135419305 HBS1L     CD3−CD4+CD8+ thymocyte, CD3+ CD4+ CD8+ thymocyte, CD4+ T cell, central memory CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, germinal center B cell, plasma cell, L-428 MYB,  MYB,  Altered T-cell differentiation (MYB)65,90, Altered B-cell differentiation and germinal center reaction (MYB),54  
6q23.3 rs6928977 135626348 AHI1   AHI1 (↑), ALDH8A1 (↑) AHI1 (CD4+ and CD8+) (↑) CD3+CD4+CD8+ thymocyte     Altered T-cell differentiation (AHI1)66  
6q23.3 rs1002658 137981584      L-428 RP11-204P2.3  TNFAIP3, TNFAIP3,78  Constitutive NF-κB activation (TNFAIP3)74  
8q24.21 rs34748721 129195943      naive B cell, class switched memory B cell CASC11, MYC, PVT1, RNU1-106P, MIR1207   MYC,91  Dysfunction of B-cell germinal center reaction (MYC)55,76  
10p14 rs2388486 8099021 GATA3   GATA3(↓)  CD3−CD4+CD8+ thymocyte, CD3+CD4+CD8+ thymocyte, CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, germinal center B cell    GATA392  Altered T-cell differentiation (GATA3),67  
10p14 rs3781093 8101927 GATA3   GATA3 (↓)  CD4+ T cell, CD8+ T cell    GATA3 Altered CD4+ T-cell differentiation (GATA3)67, Altered B-cell differentiation (GATA3)93  
11q23.1 rs7111520 111249611 POU2AF1   COLCA1 (↑), COLCA2 (↑)  CD4+ T cell, central memory CD4+ T cell, CD8+ T cell, CD38− B cell, CD38− naive B cell, naive B cell, germinal center B cell, unswitched memory B cell, class switched memory B cell, plasma cell FDX1 FDX1, PPP3R1B, ALG9, FDXACB1, DIXDC1  POU2AF194  Dysfunctional germinal center reaction (POU2AF1),56  
13q34 rs112998813 115059729 UPF3A   CDC16 (↑), UPF3A (↓) CDC16 (CD4+ and CD8+) ↑) CD4+ T cell, central memory CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, CD38− naive B cell, naïve B cell, germinal center B cell, unswitched memory B cell, class-switched memory B cell, plasma cell  RASA3, TMEM255B,, GASA6  CDC16,85  Disrupted cell cycle regulation (CDC16)95, Dysfunction of mRNA surveillance (UPF3A),96  
16p13.13 rs34972832 11198938 CLEC16A   SOCS1 (↑)  CD4+ T cell, central memory CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, naive B cell, germinal center B cell, class switched memory B cell, plasma cell, L-424 RMI2 SOCS1,, RMI2,, PRM2,, PRM3,, TNP2, HNRNPCP4 SOCS1, RMI2 SOCS180  T-cell dysfunction (SOCS1)68 ., Altered T-cell differentiation (CLEC16A)69, B-cell dysfunction (CLEC16A)97, Genomic instability (RMI2)98  
16p11.2 rs6565176 30174926 CORO1A  CORO1A (5′-UTR) MAPK3 (↓), BOLA2 (↓),  CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, naive B cell, class-switched memory B cell    MAPK3,99 CORO1A100  T-cell dysfunction (CORO1A and MAPK3)63,70,71, Dysfunction of B-cell germinal center reaction (MAPK3)57,101,102  
19p13.3 rs2012125 1630341 TCF3A     CD38− B cell, naive B cell, class-switched memory B cell     Dysfunction of B-cell germinal center reaction (TCF3A),103  
20q13.12 rs2425752 44702120 NCOA5, CD40   WFDC10B (↑)  Central memory CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, naive B cell, germinal center B cell, L-428 CD40 TP53RK  CD40104  Dysfunctional germinal center reaction (CD40)53,60, Constitutive NF-κB activation (CD40)75,76  
LocusSentinel SNPPosition, (bp, hg19)Gene(s) in LD blockCoding variant(s)Promotor/UTR variant(s)Expression quantitative trait loci in LCLsExpression quantitative trait loci in T cellH3K27Ac histone peak*Hi-C contact(s) in naive or total B cellsHi-C contact(s) in T cellsHi-C contact(s) in HRS cellEvidence of perturbation in HLCandidate biological mechanism
2p16.1 rs2420518 61054980      Naive B cell REL REL  REL84  Constitutive NF-κB activation (REL)72, Altered B-cell differentiation and germinal center reaction (REL)50  
3p24.1 rs3806624 27764623 EOMES  EOMES, (3′-UTR)  EOMES (↑) (CD8+) Effector memory CD8+ T cell, plasma cell, L-428 AZI2, CMC1, NEK10, OXSM, NGLY1, ZCWPW2 EOMES, AZI2, CMC1, NEK10, OXSM, NGLY1, ZCWPW2 AZI2, CMC1, EOMES85, Exhausted CD8 T-cell phenotype (EOMES)61,81,82, Constitutive NF-κB activation (AZI2),73  
3q28 rs4459895 187954414 LPP     CD38− naive B cell, naive B cell, germinal center B cell, L-428    BCL686  Dysfunction of B-cell germinal center reaction (BCL6, mir-28),51,52  
5q31.1 rs848 131996500 IL-13 (p.Gln144Arg) IL-13, (3′-UTR)   L-428    IL-1387  Altered CD4+ T-cell function (IL-13)62  
6p21.31 rs649775 33684313 ITPR3, UQCC2, IP6K3  IP6K3, (3′-UTR) ITPR3 (↓)  CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, naive B cell, class-switched memory B cell BAK1, SYNGAP1, GGNBP1, LINC00336 BAK1, GRM4, SYNGAP1, KIFC1, CUTA, PHF1, GGNBP1, LINC003336   Altered B-cell differentiation (ITPR3),88  
6q22.33 rs9482849 128288536 PTPRK     CD4+ T cell, central memory CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, L-428 PTPRK, THEMIS   PTPRK89  Altered T-cell differentiation (PTPRK, THEMIS),63,64  
6q23.3 rs9402684 135419305 HBS1L     CD3−CD4+CD8+ thymocyte, CD3+ CD4+ CD8+ thymocyte, CD4+ T cell, central memory CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, germinal center B cell, plasma cell, L-428 MYB,  MYB,  Altered T-cell differentiation (MYB)65,90, Altered B-cell differentiation and germinal center reaction (MYB),54  
6q23.3 rs6928977 135626348 AHI1   AHI1 (↑), ALDH8A1 (↑) AHI1 (CD4+ and CD8+) (↑) CD3+CD4+CD8+ thymocyte     Altered T-cell differentiation (AHI1)66  
6q23.3 rs1002658 137981584      L-428 RP11-204P2.3  TNFAIP3, TNFAIP3,78  Constitutive NF-κB activation (TNFAIP3)74  
8q24.21 rs34748721 129195943      naive B cell, class switched memory B cell CASC11, MYC, PVT1, RNU1-106P, MIR1207   MYC,91  Dysfunction of B-cell germinal center reaction (MYC)55,76  
10p14 rs2388486 8099021 GATA3   GATA3(↓)  CD3−CD4+CD8+ thymocyte, CD3+CD4+CD8+ thymocyte, CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, germinal center B cell    GATA392  Altered T-cell differentiation (GATA3),67  
10p14 rs3781093 8101927 GATA3   GATA3 (↓)  CD4+ T cell, CD8+ T cell    GATA3 Altered CD4+ T-cell differentiation (GATA3)67, Altered B-cell differentiation (GATA3)93  
11q23.1 rs7111520 111249611 POU2AF1   COLCA1 (↑), COLCA2 (↑)  CD4+ T cell, central memory CD4+ T cell, CD8+ T cell, CD38− B cell, CD38− naive B cell, naive B cell, germinal center B cell, unswitched memory B cell, class switched memory B cell, plasma cell FDX1 FDX1, PPP3R1B, ALG9, FDXACB1, DIXDC1  POU2AF194  Dysfunctional germinal center reaction (POU2AF1),56  
13q34 rs112998813 115059729 UPF3A   CDC16 (↑), UPF3A (↓) CDC16 (CD4+ and CD8+) ↑) CD4+ T cell, central memory CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, CD38− naive B cell, naïve B cell, germinal center B cell, unswitched memory B cell, class-switched memory B cell, plasma cell  RASA3, TMEM255B,, GASA6  CDC16,85  Disrupted cell cycle regulation (CDC16)95, Dysfunction of mRNA surveillance (UPF3A),96  
16p13.13 rs34972832 11198938 CLEC16A   SOCS1 (↑)  CD4+ T cell, central memory CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, naive B cell, germinal center B cell, class switched memory B cell, plasma cell, L-424 RMI2 SOCS1,, RMI2,, PRM2,, PRM3,, TNP2, HNRNPCP4 SOCS1, RMI2 SOCS180  T-cell dysfunction (SOCS1)68 ., Altered T-cell differentiation (CLEC16A)69, B-cell dysfunction (CLEC16A)97, Genomic instability (RMI2)98  
16p11.2 rs6565176 30174926 CORO1A  CORO1A (5′-UTR) MAPK3 (↓), BOLA2 (↓),  CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, naive B cell, class-switched memory B cell    MAPK3,99 CORO1A100  T-cell dysfunction (CORO1A and MAPK3)63,70,71, Dysfunction of B-cell germinal center reaction (MAPK3)57,101,102  
19p13.3 rs2012125 1630341 TCF3A     CD38− B cell, naive B cell, class-switched memory B cell     Dysfunction of B-cell germinal center reaction (TCF3A),103  
20q13.12 rs2425752 44702120 NCOA5, CD40   WFDC10B (↑)  Central memory CD4+ T cell, CD8+ T cell, effector memory CD8+ T cell, naive B cell, germinal center B cell, L-428 CD40 TP53RK  CD40104  Dysfunctional germinal center reaction (CD40)53,60, Constitutive NF-κB activation (CD40)75,76  
*

SNPs (r2 < 2.5 kilobases from ChIP-seq peak).

View Large
Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal