DataSheet_1_Decoupling blood telomere length from age in recipients of allogeneic hematopoietic cell transplant in the BMT-CTN 1202.docx

The age of allogeneic hematopoietic cell transplant (HCT) donors and their hematopoietic cell telomere length (TL) might affect recipients’ outcomes. Our goals were to examine the possible effect of these donors’ factors on the recipients’ hematopoietic cell TL and quantify hematopoietic cell TL shortening in the critical first three-month post-HCT. We measured hematopoietic cell TL parameters in 75 recipient-donor pairs, from the Blood and Marrow Transplant Clinical Trials Network (protocol#1202), by Southern blotting (SB), the Telomeres Shortest Length Assay (TeSLA), and quantitative PCR (qPCR). Recipients’ hematopoietic cell TL parameters post-HCT correlated with donors’ age (p0.0001 for all). SB and TeSLA detected hematopoietic cell TL shortening in all recipients post-HCT (mean=0.52kb and 0.47kb, respectively; >15-fold the annual TL shortening in adults; p<0.00001 for both), but qPCR detected shortening only in 57.5% of recipients. TeSLA detected a buildup of post-HCT of telomeres <3 kb in 96% of recipients (p<0.0001). In conclusion, HCT decouples hematopoietic cell TL in the recipients from their own age to reflect the donors’ age. The potential donors’ age effect on outcomes of HCT might be partially mediated by short hematopoietic cell TL in older donors. qPCR-based TL measurement is suboptimal for detecting telomere shortening post-HCT.</p

Observed and expected distributions for the P values of linear trend for 3,985 tag-SNPs in 230 gene regions related to immune function in a case-control study of PTC risk.

<p>Observed and expected distributions for the P values of linear trend for 3,985 tag-SNPs in 230 gene regions related to immune function in a case-control study of PTC risk.</p

Characteristics of the study population by case and control status, U. S. Radiologic Technologists Study and University of Texas M. D. Anderson Cancer Center Study.

a<p>Test of independence.</p>b<p>As of referent age. See text for description of referent age assignment.</p>c<p>Adjusted for sex and attained age.</p

Linkage disequlibrium (LD) representation of the <i>SERPINA5</i> gene.

<p>The figure represents LD based on the genotyping data from the study controls with European ancestry. LD is measured by D′ parameters (top panel) and the r² correlation coefficient (bottom panel). D′ and r² values of one are interpreted as complete LD.</p

Pathway-based significance levels (<i>P</i> values) for each immunity pathway analyzed, with and without accounting for overlapping genes between pathways.

a<p>Some gene regions were allocated to more than one pathway, creating overlap. To calculate <i>P</i> values without overlap in multiple pathway allocations, these specific gene regions were dropped from their respective pathways.</p>b<p>Pathway-based <i>P</i> values (<i>P_Pathway</i>) were calculated using the adaptive rank truncated product method.</p

Significance levels (<i>P</i> values) for an association with papillary thyroid cancer for the selected gene regions with uncorrected <i>P_Region</i> <0.01.

a<p>Gene region-based <i>P</i> values (<i>P_Region</i>) calculated using the adaptive rank truncated product method.</p>b<p>False discovery rate (FDR) corrected <i>P_Region</i>.</p

Odds ratio and 95% confidence interval (CI), adjusted for sex, attained age, and year of birth, for the tag SNPs associated with papillary thyroid cancer risk at <i>P_SNP-trend</i> <0.001.

a<p>SNP-based linear <i>P_SNP-trend</i> is calculated based on the three-level genotype (0, 1, and 2) in logistic regression models adjusted for sex, attained age, and year of birth.</p>b<p>False discovery rate (FDR) corrected linear <i>P_SNP-trend</i>.</p

Distribution of characteristics of study subjects.

<p>Numbers might no add to totals due to missing values. Data might not add up to 100% because of rounding.</p>*<p>Not measured in the family study.</p

Gene-based association analysis with the risk of melanoma.

*<p>Based on a meta-analysis of the three case-control studies and one family study. Model was adjusted for age (continous) and sex. Genes ordered from most significant to least significant associations with outcome.</p

Gene-based association analysis and risk of dysplastic nevi and number of nevi in unaffected subjects.

*<p>Based on a meta-analysis of the 3 case-control studies and the family study. Model was adjusted for age (continous) and sex.</p>**<p>Based on a meta-analysis of case-control study and the family study using Poisson regression with robust variance. Model was adjusted for age (continous) and sex and interaction between age and SNP genotype. Genes ordered from the most to the least significant P-value.</p