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Participants (775) selected from a 2\u2010year longitudinal study were classified into six analysis groups based on sex, donation intensity, and low hemoglobin deferral. Associations with iron supplement use, cigarette smoking, and four genetic variants of iron metabolism were examined at enrollment and with longitudinal regression models. An unbiased assessment of genetic variability and ability to repeatedly donate blood without experiencing low hemoglobin deferral was conducted on participants (13,403) in a cross\u2010sectional study who were examined by genome wide association (GWA).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Behaviors and genetic variants were associated with differences in hemoglobin and ferritin change following repeated donation. At least weekly iron supplement use was associated with improved status in first\u2010time donors, while daily use was associated with improved status in high\u2010intensity donors. Cigarette smoking was associated with 0.5 g\/dL increased hemoglobin in high\u2010intensity donors. A736V in <jats:italic>TMPRSS6<\/jats:italic> was associated with a rapid drop in hemoglobin and ferritin in first\u2010time females following repeated donation. Conversely, the protective <jats:italic>TMPRSS6<\/jats:italic> genotype was not enriched among high\u2010intensity donors. H63D in <jats:italic>HFE<\/jats:italic> was associated with increased hemoglobin in female high\u2010intensity donors. However, no differences in genotype between first\u2010time and high\u2010intensity donors were found in GWA analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Behavioral and genetic modifiers contributed to first\u2010time donor hemoglobin and iron status, while iron supplement use was more important than underlying genetics in high\u2010intensity donors.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.15743","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T09:13:58Z","timestamp":1584004438000},"page":"747-758","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Genetic and behavioral modification of hemoglobin and iron status among first\u2010time and high\u2010intensity blood donors"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3740-0318","authenticated-orcid":false,"given":"Alan 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