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Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences.

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.

Among 397,640 first-time blood donors screened in South Africa during 2012-2015, HIV prevalence was 1.13%, hepatitis B virus prevalence 0.66%, and hepatitis C virus prevalence 0.03%. Findings of note were a high HIV prevalence in Mpumalanga Province and the near absence of hepatitis C virus nationwide.

BackgroundFalse-positive infectious transfusion screening results remain a challenge with continued loss of both donors and blood products. We sought to identify associations between donor demographic characteristics (age, race, sex, education, first-time donor status) and testing false positive for viruses during routine blood donation screening. In addition the study assessed the prevalence of high-risk behaviors in false-positive donors.Study design and methodsBlood Systems, Inc. donors with allogeneic donations between January 1, 2011, and December 31, 2012, were compared in a case-control study. Those with a false-positive donation for one of four viruses (human immunodeficiency virus [HIV], human T-lymphotropic virus [HTLV], hepatitis B virus [HBV], and hepatitis C virus [HCV]) were included as cases. Those with negative test results were controls. For a subset of cases, infectious risk factors were evaluated.ResultsBlack race and Hispanic ethnicity were associated with HCV and HTLV false-positive results. Male sex and lower education were associated with HCV false positivity, and age 25 to 44 was associated with HTLV false positivity. First-time donors were more likely to be HCV false positive although less likely to be HBV and HTLV false positive. No significant associations between donor demographics and HIV false positivity were observed. A questionnaire for false-positive donors showed low levels of high-risk behaviors.ConclusionDemographic associations with HCV and HTLV false-positive results overlap with those of true infection. While true infection is unlikely given current testing algorithms and risk factor evaluation, the findings suggest nonrandom association. Further investigation into biologic mechanisms is warranted.

Background: Studies preceding the COVID‐19 pandemic found that slower time‐to‐return was associated with first‐time, deferred, and mobile drive blood donors. How donor return dynamics changed during the COVID‐19 pandemic is not well understood. Methods: We analyzed visits by whole blood donors from 2017 to 2022 in South Africa (SA) and the United States (US) stratified by mobile and fixed environment, first‐time and repeat donor status, and pre‐COVID19 (before March 2020) and intra‐COVID19. We used Kaplan–Meier curves to characterize time‐to‐return, cumulative incidence functions to analyze switching between donation environments, and Cox proportional hazards models to analyze factors influencing time‐to‐return. Results: Overall time‐to‐return was shorter in SA. Pre‐COVID19, the proportion of donors returning within a year of becoming eligible was lower for deferred donors in both countries regardless of donation environment and deferral type. Intra‐COVID19, the gap between deferred and non‐deferred donors widened in the US but narrowed in SA, where efforts to schedule return visits from deferred donors were intensified, particularly for non‐hemoglobin‐related deferrals. Intra‐COVID19, the proportion of donors returning within a year in SA was higher for deferred first‐time donors (>81%) than for successful first‐time donors (80% at fixed sites; 69% at mobile drives). Conclusions: The pandemic complicated efforts to recruit new donors and schedule returning visits after completed donations. Concerted efforts to improve time‐to‐return for deferred donors helped mitigate donation loss in SA during the public health emergency. [ABSTRACT FROM AUTHOR]

BackgroundBlood banks have large altruistic donor populations and existing infrastructure that make them attractive sites for genetic epidemiologic research, but donors' willingness to participate and the impact on blood donation are unknown.Study design and methodsA total of 2162 blood donors in Northern California responded to a cross-sectional questionnaire in August and September 2007. Participants were asked their likelihood of participation and future blood donation under three different scenarios: identity-linked genetic research, identity-unlinked genetic research, and genetic testing as a service.ResultsThe majority of blood donors indicated that they would be likely or very likely to participate in identity-linked genetic research (67%) and in identity-unlinked genetic research (54%). While older donors and more frequent donors were more likely to participate in identity-linked research, younger, Caucasian, more educated, and more frequent donors were more likely to participate in identity-unlinked research. Less than 10% of donors indicated they would be less likely to donate blood in the future if genetic research was conducted at blood banks. More than 75% of donors would be interested in genetic testing as an optional service at the blood bank, but more than 20% of donors would be less likely to donate if such a service was offered.ConclusionOverall, we found that the majority of blood donors would be likely to participate in genetic research and that less than 10% would be less inclined to donate if such research was conducted by blood banks.

BackgroundHistorically, minority populations have represented only a small proportion of US blood donors, but recent trends in immigration and potential blood shortages emphasize the need for recruitment strategies to increase minority donations.Study design and methodsDonation data from a network of six US blood centers for 2006 were analyzed. Race/ethnicity, country of birth, and educational attainment data were collected specifically for the study and assessed for their influence on donation behavior. Logistic regression was used to determine independent associations with repeat donors status and annual donation frequency.ResultsA total of 1,288,998 donations from 729,068 donors were studied; most donors had data on race/ethnicity (97.1%) and country of birth (93.1%). The proportion of minority donors differed by blood center, with African American donors (16%) most common at the Southeastern blood center and Asian (12%), Hispanic (13%), and foreign-born donors (13%) most common at the Northern California blood center. Minority donors and those born in Mexico or Latin America were younger than white donors. Minority and non-US-born donors were less likely than white and US-born donors to be repeat donors (odds ratio [OR], 0.60-0.78), and most were less likely to give two or more annual donations (OR, 0.82-1.11).ConclusionMinority and Mexico/Latin America-born donors represent a younger and often first-time donor population compared to white and US-born donors, but their annual donation frequency was only slightly lower than white and US-born donors. Increasing the retention and donation frequency of minorities will be important for supplementing the blood supply.

Background and Objectives: Efficiency in mitigating HIV transmission risk by transfusion may vary internationally. We compared HIV prevalence and incidence in blood donors across different jurisdictions in relation to those rates in the general population and differences in deferral practices. Materials and Methods: Data from 2007 to 2016 were collected in Australia, Brazil (São Paulo), Canada, England, France, Italy, Ireland, Japan, the Netherlands, New Zealand, Norway, Spain (Basque Country), USA (Vitalant) and Wales. For each country/region, the number of HIV antibody‐positive donations and nucleic acid testing (NAT)‐only‐positive donations was broken down according to first‐time or repeat donor status, along with the relevant denominators. Results: There is a modest correlation between HIV prevalence among first‐time donors and HIV prevalence in the general population. However, rates of HIV‐positive donations in repeat donors, a proxy for incidence, do not correlate with incidence rates in the general population. Rates in donors from Italy and Basque Country, where deferral criteria for men having sex with men are less stringent, are higher compared with most other jurisdictions. Rates of NAT‐only‐positive donations are extremely low and do not differ significantly after adjustment for multiple comparisons. Conclusion: Donor HIV rates are only weakly associated with those observed in the general population. Countries with less stringent deferral criteria have higher HIV rates in their donor population, but the rates remain very low. [ABSTRACT FROM AUTHOR]

Abstract Background Payments for red blood cell (RBC) transfusions are separate from US Medicare bundled payments for dialysis-related services and medications. Our objective was to examine the economic burden for payers when chronic dialysis patients receive outpatient RBC transfusions. Methods Using Truven Health MarketScan® data (1/1/02-10/31/10) in this retrospective micro-costing economic analysis, we analyzed data from chronic dialysis patients who underwent at least 1 outpatient RBC transfusion who had at least 6 months of continuous enrollment prior to initial dialysis claim and at least 30 days post-transfusion follow-up. A conceptual model of transfusion-associated resource use based on current literature was employed to estimate outpatient RBC transfusion payments. Total payments per RBC transfusion episode included screening/monitoring (within 3 days), blood acquisition/administration (within 2 days), and associated complications (within 3 days for acute events; up to 45 days for chronic events). Results A total of 3283 patient transfusion episodes were included; 56.4% were men and 40.9% had Medicare supplemental insurance. Mean (standard deviation [SD]) age was 60.9 (15.0) years, and mean Charlson comorbidity index was 4.3 (2.5). During a mean (SD) follow-up of 495 (474) days, patients had a mean of 2.2 (3.8) outpatient RBC transfusion episodes. Mean/median (SD) total payment per RBC transfusion episode was $854/$427 ($2,060) with 72.1% attributable to blood acquisition and administration payments. Complication payments ranged from mean (SD) $213 ($168) for delayed hemolytic transfusion reaction to $19,466 ($15,424) for congestive heart failure. Conclusions Payments for outpatient RBC transfusion episodes were driven by blood acquisition and administration payments. While infrequent, transfusion complications increased payments substantially when they occurred.