Erik Sørensen

Predictors of iron levels in 14,737 Danish blood donors: results from the Danish Blood Donor Study

Dietary studies show a relationship between the intake of iron enhancers and inhibitors and iron stores in the general population. However, the impact of dietary factors on the iron stores of blood donors, whose iron status is affected by blood donations, is incompletely understood.

The Danish Blood Donor Study: a large, prospective cohort and biobank for medical research

Dear Editor, The possibilities of repurposing blood donor sample repositories for establishing large-scale biobanks have attracted increasing interest among blood banks in recent years [1, 2], Most countries routinely store plasma specimens from blood donations to meet the requirements for good manufacturing practice. In some countries, this plasma has successfully been used for research purposes [2–4]. In Denmark, we designed an ambitious solution for establishing a large-scale research project and biobank – the Danish Blood Donor Study (DBDS). The DBDS, like other blood donor biobanks, relies on existing infrastructure for standardized data collection, handling and storage of plasma samples in the blood banks. Therefore, we can process research samples for a large-scale biobank at a minimal cost. However, in contrast to most other blood donor biobanks, we also collect questionnaire data and DNA on all participating donors. The immediate focus of the DBDS is to answer why some blood donors are healthier and donate longer than others. However, the DBDS is ultimately intended as a general platform for collaborative research. The long-term perspective is that some blood donors will eventually develop disease; the availability of DNA, prediagnostic plasma and baseline questionnaire data will become a valuable resource for future research on disease biomarkers. Blood donors are invited to participate in the study at all blood banks in the Capital and Central Denmark Regions. Specifically, the local staff informs the blood donor of the study during the blood donation. If the donor agrees to participate, he or she signs a consent form and completes a four-page questionnaire on health-related issues including health-related quality-of-life (SF-12), smoking habits, alcohol intake, exercise, food intake, supplemental iron intake, height, weight and waist circumference measurements. All participating donors grant permission to collect data on health and demographics from public registries and allow us to contact them again for acquisition of additional data. Finally, the blood donors consent to the use of look-back blood samples for DBDS research. We are currently isolating DNA from the first 20 000 blood donors. Since the launch of the project in March 2010, we have included more than 40 000 blood donors in the study. Less than 5% of the invited blood donors decline to participate. To speed up the inclusion process further, we plan to extend the study to the whole country with the potential of including more than 250 000 donors. In conclusion, the DBDS shows that it is feasible to establish a large prospective epidemiological research cohort within the blood bank system at a low cost. Because of the prospective design, the description of blood donors can include a variety of data to reveal subtle connections between risk factors, biomarkers, health and disease.

Combined Oral Contraception and Obesity Are Strong Predictors of Low-Grade Inflammation in Healthy Individuals: Results from the Danish Blood Donor Study (DBDS)

Background C-reactive protein (CRP) is a well-established marker of inflammation. The level of CRP is affected by several lifestyle factors. A slightly increased CRP level, also known as low-grade inflammation (LGI), is associated with increased risk of several diseases, especially cardiovascular disease. The aim of this study was to identify predictors of increased CRP levels in healthy individuals. We therefore assessed CRP in a large cohort of blood donors. Methods We measured plasma CRP levels in 15,684 participants from the Danish Blood Donor Study. CRP was measured by a commercial assay. Furthermore, all participants completed a standard questionnaire on smoking status, alcohol consumption, physical activity, diet, and various body measurements. Female participants also reported the use of contraception, childbirth, and menopausal status. The relationship between LGI (defined here as a plasma CRP level between 3 mg/L and 10 mg/L) and predictors was explored by multivariable logistic regression analysis. Results were presented as odds ratios (OR) with 95% confidence intervals (CI). Results We found LGI in a total of 1,561 (10.0%) participants. LGI was more frequent in women using combined oral contraception (OC) (29.9%) than in men (6.1%) and women not using OC (7.9%). Among premenopausal women, OC was the strongest predictor of LGI (odds ratio = 8.98, p<0.001). Additionally, body mass index (BMI) and waist circumference were positively associated with LGI. Conclusion High BMI and abdominal obesity strongly predicted LGI among healthy individuals. However, the most striking finding was the high prevalence of LGI among premenopausal women who used combined oral contraception. Although the significance of CRP as a marker of inflammation is well known, the role of CRP in pathogenesis is still uncertain. The impact of oral contraception on CRP levels should nevertheless be considered when CRP is used in risk assessment.

Obesity and risk of infection: results from the Danish Blood Donor Study.

Background: It is well known that obesity complicates the course of several diseases. However, it is unknown whether obesity affects the risk of infection among healthy individuals. Methods: We included 37,808 healthy participants from the Danish Blood Donor Study, who completed a questionnaire on health-related items. Obesity was defined as a body mass index ≥ 30 kg/m2. Infections among participants were identified by relevant ICD-10 codes in the Danish National Patient Register and Anatomical Therapeutic Chemical (ATC) codes in the Danish Prescription Register. Multivariable Cox proportional hazards analysis with age as the underlying timescale was used as the statistical model. Results: During 113,717 person-years of observation, 1,233 participants were treated for infection at a hospital. Similarly, during 58,411 person-years of observation, 15,856 participants filled at least one prescription of antimicrobials. Obesity was associated with risk of hospital-based treatment for infection (women: hazard ratio [HR] = 1.5, 95% confidence interval [CI] = 1.1, 1.9; men: HR = 1.5, 95% CI = 1.2, 1.9). For specific infections, obesity was associated with increased risk of abscesses (both sexes), infections of the skin and subcutaneous tissue (men), and respiratory tract infections and cystitis (women). Similarly, obesity was associated with filled prescriptions of antimicrobials overall (women: HR = 1.22, 95% CI = 1.14, 1.30; men: HR = 1.23, 95% CI: 1.15, 1.33) and particularly with phenoxymethylpenicillin, macrolides, dicloxacillin and flucloxacillin, and broad-spectrum penicillins. Conclusions: In a large cohort of healthy individuals, obesity was associated with risk of infection. This result warrants further studies of metabolism and the immune response.

A genetic risk factor for low serum ferritin levels in Danish blood donors

BACKGROUND: Iron deficiency is a frequent side effect of blood donation. In recent years, several studies have described genetic variants associated with iron concentrations. However, the impact of these variants on iron levels is unknown in blood donors. Knowledge of genetic variants that predispose donors to iron deficiency would allow bleeding frequency and iron supplementation to be tailored to the individual donor.

Genetic analyses of the human eye colours using a novel objective method for eye colour classification

In this study, we present a new objective method for measuring the eye colour on a continuous scale that allows researchers to associate genetic markers with different shades of eye colour. With the use of the custom designed software Digital Iris Analysis Tool (DIAT), the iris was automatically identified and extracted from high resolution digital images. DIAT was made user friendly with a graphical user interface. The software counted the number of blue and brown pixels in the iris image and calculated a Pixel Index of the Eye (PIE-score) that described the eye colour quantitatively. The PIE-score ranged from -1 to 1 (brown to blue). The software eliminated the need for user based interpretation and qualitative eye colour categories. In 94% (570) of 605 analyzed eye images, the iris region was successfully extracted and a PIE-score was calculated. A very high correlation between the PIE-score and the human perception of eye colour was observed. The correlations between the PIE-scores and the six IrisPlex SNPs (HERC2 rs12913832, OCA2 rs1800407, SLC24A4 rs12896399, TYR rs1393350, SLC45A2 rs16891982 and IRF4 rs12203592) were analyzed in 570 individuals. Significant differences (p<10(-6)) in the PIE-scores of the individuals typed as HERC2 rs12913832 G (PIE=0.99) and rs12913832 GA (PIE=-0.71) or A (PIE=-0.87) were observed. We adjusted for the effect of HERC2 rs12913832 and showed that the quantitative PIE-scores were significantly associated with SNPs with minor effects (OCA2 rs1800407, SLC24A4 rs12896399 and TYR rs1393350) on the eye colour. We evaluated the two published prediction models for eye colour (IrisPlex [1] and Snipper[2]) and compared the predictions with the PIE-scores. We found good concordance with the prediction from individuals typed as HERC2 rs12913832 G. However, both methods had difficulties in categorizing individuals typed as HERC2 rs12913832 GA because of the large variation in eye colour in HERC2 rs12913832 GA individuals. With the use of the DIAT software and the PIE-score, it will be possible to automatically compare the iris colour of large numbers of iris images obtained by different studies and to perform large meta-studies that may reveal loci with small effects on the eye colour.

Mitochondrial DNA HV1 and HV2 variation in Danes

Sequences from the two hypervariable regions (HV1 and HV2) of the control region of the mitochondrial DNA were obtained from a total of 201 Danes and five individuals who later were recognized to be of non-West European origin. Two fractions of each region were amplified separately and sequenced at least twice. The samples were sequenced using flanking sequencing primes and both terminator and primer chemistry. Sequence evaluation was performed by two independent scientists. The haplogroup distribution of the samples resembles that found in other European population. All the sequences have been made available in the EMPOP database.

No association between iron status and self-reported health-related quality of life in 16,375 Danish blood donors: results from the Danish Blood Donor Study.

Health‐related quality of life (HRQL) represents peoples subjective assessment of their mental and physical well‐being. HRQL is highly predictive of future health. The effect of iron deficiency without anemia induced by blood donation on HRQL is presently unknown. The aim was to explore the relationship between iron status and self‐reported mental component score (MCS; SF‐12) and physical component score (PCS; SF‐12) in Danish blood donors.

Predictors of hemoglobin in Danish blood donors: results from the Danish Blood Donor Study.

It is well known that blood donors are at increased risk of iron deficiency and subsequent development of iron deficiency anemia. We aimed to investigate the effect of factors influencing hemoglobin (Hb) levels.

Conjugation in aquatic environments

Concerns with the horizontal exchange of genetic material by conjugation in aquatic environments arise from two issues. The first relates to conjugation as a mechanism that promotes genetic and physiological diversity in the aquatic microbial community [24]. The second arises from the need to regulate applications of genetically engineered microbes (GEMs) in environmental management practices [11, 14]. An understanding of conjugation in situ is needed to address both issues and this necessitates the development of experimental approaches and methods that enable following conjugal gene transfer among aquatic microbial populations in their natural habitats.