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Host genomics of HIV-related lymphoma
No replication of susceptibility loci found in the general population
In order to assess whether the genetic contribution to the risk of developing NHL is similar or distinct in the HIV+ population compared to the general population, we extracted the P-values of all variants found to be genome- wide significant in previous GWAS performed in the gen- eral population14,21–24,43 and compared them to our results. We did not replicate any of the previously published genome-wide associated variants, even at nominal signifi- cance level (P<0.05), despite sufficient statistical power for many of the variants, thus indicating that the genetic sus- ceptibility of NHL is distinct between the HIV+ and the general population (Online Supplemental Table S3). In order to further examine this possibility, we tested whether the NHL/HIV+ associated variant rs7919208 is associated
A
Table 2. Significant association with human immunodeficiency virus-related non-Hodgkin lymphoma.
Chr Pos SNP Ref Alt P OR
10 44673557
10 44677967 10 44678218 10 44678262 10 44678454 10 44678898
10 44680902
rs7919208
rs149399290
rs17155463
rs17155474
rs17155478
rs12249837
rs10608969
A G
T C
T A
C T
T C
G A
T TAAAGA
4.77e-11 1.23
3.09e-08 1.20
3.09e-08 1.20
3.09e-08 1.20
3.09e-08 1.20
3.09e-08 1.20
3.09e-08 1.20
B
Variants significantly associated with human immunodeficiency virus (HIV)-related non- Hodgkin lymphoma in a weighted Z-score-based meta-analysis of all individuals included in the Swiss HIV Cohort Study (SHCS), the Primo ANRS and ANRS CO16 Lymphovir cohorts (ANRS) and the Multicenter AIDS Cohort Study (MACS) cohorts. Odds ratios (OR) were trans- formed from betas using the formula OR=exp(beta). Chr: chromosome; pos: position; SNP: sin- gle nucleotide polymorphisms; Ref: reference allele, Alt: alternative allele.
Figure 2. Fine mapping of genome- wide significant hits with PAINTOR. (A) The 99% credible set and poste- rior probabilities of being the causal variant. The genomic posi- tions are listed on the x-axis. Bottom tracks represent DNAase and chromatin marks obtained from GM12878 cells as well as transcription factor binding site (TFBS) from the Roadmap Epigenomics Project and ENCODE in the region. (B) Locus plot of the associated variants, highlighting the LD relationship, based on the Swiss HIV Cohort Study cohort. The top variant rs7919208 is marked by a black diamond.
haematologica | 2021; 106(8)
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