Population-based Biobanks Research Articles

Reverse Discrimination For Psychiatric Genetic Studies In Population-Based Biobanks

The results of genome-based research are increasingly becoming part of planning for care. The question remains whether the results of this research are representative, since it often excludes people with psychiatric conditions. Despite best intentions, in our desire to protect the vulnerable, we risk creating a situation where they are discriminated against in a double sense: non-inclusion to protect them from the risks of research leads to biased results, that in turn could lead to a lower standard of care in the future.Large-scale population biobanking projects link genetic data with the information participants provide regarding their health status, lifestyle (including alcohol consumption, smoking, etc.) and known environmental factors. The collection of samples and data constitutes the basis for future research projects on two levels. First, some diseases or phenotypes are collected with great precision during the recruitment for existing research protocols. Second, follow up projects are planned based on the analysis of data collected from questionnaires and analysis of biological specimens on the basis of identified phenotypes. Often, these data make it possible to assess and identify diseases ranging from diabetes to depression. Once a condition is identified, researchers need to collect further phenotypes or dig deeper into a recognized pattern.Commonly, participants in population cohorts are recruited for studies of common diseases. For example, there is a large number of cohorts focused on cardiovascular and metabolic conditions. Recruitment of population cohorts often excludes incapacitated individuals and people who, for several reasons, cannot provide a full informed consent. This means minors are often excluded from population cohorts and (sometimes) instead collected separately in biobanks for children. Against this background, it becomes obvious that there is a problem of representativeness for these categories of people that constitute an already known first bias in the collections. The reason for this is often administrative: handling issues of legal representatives may in fact prove to be too complicated on a population level.There is, however, a second layer of possible bias that arises in the planning of follow up research projects. Planning to re-call people with severe depression, addiction or initial stages of degenerative conditions (dementia, etc.), often entails several layers of ethical and logistical issues that do not arise in re-contact of participants with suspected diabetes or leukemia.If we use depression as an example, this problem becomes apparent. When people suspected to have depression are invited to participate in follow up research with a physician, they are asked to fill out questionnaires used to diagnose depression and identify suicide risks. Costly follow up visits with specialists are needed if a research participant discloses that he or she is contemplating suicide. For people with early stage dementia, the problem is more related to information and ability to pay attention, and the difficulties associated with explaining and understanding large amounts of complex information.This presentation will provide an overview of possible discriminatory patterns that jeopardize the possibility for psychiatric patients (in a very broad sense) to benefit from the potential of biobank-based research, with some case examples.

Comprehensive population-based genome sequencing provides insight into hematopoietic regulatory mechanisms

Genetic variants affecting hematopoiesis can influence commonly measured blood cell traits. To identify factors that affect hematopoiesis, we performed association studies for blood cell traits in the population-based Estonian Biobank using high-coverage whole-genome sequencing (WGS) in 2,284 samples and SNP genotyping in an additional 14,904 samples. Using up to 7,134 samples with available phenotype data, our analyses identified 17 associations across 14 blood cell traits. Integration of WGS-based fine-mapping and complementary epigenomic datasets provided evidence for causal mechanisms at several loci, including at a previously undiscovered basophil count-associated locus near the master hematopoietic transcription factor CEBPA The fine-mapped variant at this basophil count association near CEBPA overlapped an enhancer active in common myeloid progenitors and influenced its activity. In situ perturbation of this enhancer by CRISPR/Cas9 mutagenesis in hematopoietic stem and progenitor cells demonstrated that it is necessary for and specifically regulates CEBPA expression during basophil differentiation. We additionally identified basophil count-associated variation at another more pleiotropic myeloid enhancer near GATA2, highlighting regulatory mechanisms for ordered expression of master hematopoietic regulators during lineage specification. Our study illustrates how population-based genetic studies can provide key insights into poorly understood cell differentiation processes of considerable physiologic relevance.

Population-based imaging biobanks as source of big data.

Advances of computational sciences over the last decades have enabled the introduction of novel methodological approaches in biomedical research. Acquiring extensive and comprehensive data about a research subject and subsequently extracting significant information has opened new possibilities in gaining insight into biological and medical processes. This so-called big data approach has recently found entrance into medical imaging and numerous epidemiological studies have been implementing advanced imaging to identify imaging biomarkers that provide information about physiological processes, including normal development and aging but also on the development of pathological disease states. The purpose of this article is to present existing epidemiological imaging studies and to discuss opportunities, methodological and organizational aspects, and challenges that population imaging poses to the field of big data research.

Pre-diagnostic Serum Concentrations of Organochlorines and Risk of Myeloid Leukemia: a Nested Case-Control Study in the Norwegian Janus Serum Bank Cohort

Introduction: Organochlorines (OCs) are structurally diverse and environmentally persistent chemicals that are widespread contaminants. Some OC pesticides and polychlorinated biphenyl (PCBs) congeners have been associated with lymphoid neoplasms. While an association between OC exposure and risk of myeloid leukemia (ML) is biologically plausible and suggestive based on observations in occupationally exposed individuals, associations between serum levels of OCs and risk of ML in the general population have not been evaluated prospectively. Methods: We conducted a nested case-control study within the Janus cohort, a population-based biobank consisting of serum samples collected in the time period 1972-2004 from ~318,000 individuals in Norway. Risk of ML in relation to lipid-adjusted levels of 11 OC pesticide metabolites and 34 PCB congeners was evaluated in 76 ML cases and 353 controls. Odds ratios (ORs) and 95% confidence intervals (CI) were computed and associations were adjusted for sex, county, age and date at blood draw, smoking, and BMI. Results: Higher levels of total chlordane/heptachlor metabolites were associated with future risk of ML in continuous (OR = 1.2, 95% CI = 1.0-1.5 per unit increase in the log-transformed concentration (ng/g lipid)) and tertile analyses (3rd vs. 1st tertile OR = 2.0, 95% CI = 0.9-4.6). The association was strongest for oxychlordane (OR = 1.9, 95% CI = 1.2-2.9 per unit increase in the log-transformed concentration (ng/g lipid); 3rd vs. 1st tertile OR = 2.2, 95% CI = 1.0-4.9), and a suggestive association with ML risk was also observed for higher levels of heptachlor epoxide (3rd vs. 1st tertile OR = 2.0, 95% CI = 0.9-4.5). No consistent associations with ML risk were observed for other OC pesticide metabolites or for PCBs. Conclusions: Our data provide evidence that metabolites of chlordane/heptachlor may be associated with future risk of ML. Studies with a larger number of ML cases are needed to follow-up on these findings.

The Geisinger MyCode® Community Health Initiative: Experiences in Patient Recruitment, Genomic Sequencing, and Patient Engagement in a Population-Based Biobank

The Geisinger MyCode® Community Health Initiative: Experiences in Patient Recruitment, Genomic Sequencing, and Patient Engagement in a Population-Based Biobank

Abstract 4039: Mimotope variance analysis: A novel immunoprofiling method to monitor progression of cervical cancer

Abstract The purpose of the study was to identify and describe cervical cancer specific changes in humoral immune response by using a novel technology platform Mimotope Variation Analysis (MVA) developed by Protobios. The Janus Serum Bank is one of the world's oldest and largest population-based research biobanks established in 1973. The cohort is annually linked to the Cancer Registry of Norway using personal identification numbers. More than 1000 women have developed cervical cancer after donating sera. We identified sets of successive sera samples from ten patients with invasive cervical cancer, ten patients with pre-invasive cervical neoplasia and twenty cancer-free individuals (matched for age, gender, length of sample storage +3 months). For each subject we identified 4-10 samples donated to Janus over a period of up to 18 years, in total 213 samples. We applied MVA which combines phage display technology and high-throughput sequencing analysis to generate quantitative serologic profiles of millions of 12-mer peptide antigens called mimotopes from 2 μl of blood serum per analysis. Hierarchical clustering analysis of the top 5000 mimotopes from each sample resulted in individual-specific immunoprofiles. Multiple samples from the same person clustered together. Moreover, clustering reflected the time the sera was drawn suggesting that part of the individual immunoprofile is stabile over time. In conclusion, preliminary results suggests that Mimotope Variance Analysis generates individual-specific immunological profiles. This profile most likely reflect prior exposure environmental pathogens. Further, we aim to decode the differences in the immunological profiles between cancer patients and cancer-free subjects. Citation Format: Espen Enerly, Mari Nygård, Madleen Orumaa, Arno Pihlak, Susan Pihelgas, Hilde Langseth, Toomas Neuman, Kaia Palm. Mimotope variance analysis: A novel immunoprofiling method to monitor progression of cervical cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4039.

Copy number variation analysis detects novel candidate genes involved in follicular growth and oocyte maturation in a cohort of premature ovarian failure cases.

STUDY QUESTIONCan spontaneous premature ovarian failure (POF) patients derived from population-based biobanks reveal the association between copy number variations (CNVs) and POF?SUMMARY ANSWERCNVs can hamper the functional capacity of ovaries by disrupting key genes and pathways essential for proper ovarian function.WHAT IS KNOWN ALREADYPOF is defined as the cessation of ovarian function before the age of 40 years. POF is a major reason for female infertility, although its cause remains largely unknown.STUDY DESIGN, SIZE, DURATIONThe current retrospective CNV study included 301 spontaneous POF patients and 3188 control individuals registered between 2003 and 2014 at Estonian Genome Center at the University of Tartu (EGCUT) biobank.PARTICIPANTS/MATERIALS, SETTING, METHODSDNA samples from 301 spontaneous POF patients were genotyped by Illumina HumanCoreExome (258 samples) and HumanOmniExpress (43 samples) BeadChip arrays. Genotype and phenotype information was drawn from the EGCUT for the 3188 control population samples, previously genotyped with HumanCNV370 and HumanOmniExpress BeadChip arrays. All identified CNVs were subjected to functional enrichment studies for highlighting the POF pathogenesis. Real-time quantitative PCR was used to validate a subset of CNVs. Whole-exome sequencing was performed on six patients carrying hemizygous deletions that encompass genes essential for meiosis or folliculogenesis.MAIN RESULTS AND THE ROLE OF CHANCEEleven novel microdeletions and microduplications that encompass genes relevant to POF were identified. For example, FMN2 (1q43) and SGOL2 (2q33.1) are essential for meiotic progression, while TBP (6q27), SCARB1 (12q24.31), BNC1 (15q25) and ARFGAP3 (22q13.2) are involved in follicular growth and oocyte maturation. The importance of recently discovered hemizygous microdeletions of meiotic genes SYCE1 (10q26.3) and CPEB1 (15q25.2) in POF patients was also corroborated.LIMITATIONS, REASONS FOR CAUTIONThis is a descriptive analysis and no functional studies were performed. Anamnestic data obtained from population-based biobank lacked clinical, biological (hormone levels) or ultrasonographical data, and spontaneous POF was predicted retrospectively by excluding known extraovarian causes for premature menopause.WIDER IMPLICATIONS OF THE FINDINGSThe present study, with high number of spontaneous POF cases, provides novel data on associations between the genomic aberrations and premature menopause of ovarian cause and demonstrates that population-based biobanks are powerful source of biological samples and clinical data to reveal novel genetic lesions associated with human reproductive health and disease, including POF.STUDY FUNDING/COMPETING INTERESTThis study was supported by the Estonian Ministry of Education and Research (IUT20-43, IUT20-60, IUT34-16, SF0180027s10 and 9205), Enterprise Estonia (EU30020 and EU48695), Eureka's EUROSTARS programme (NOTED, EU41564), grants from European Union's FP7 Marie Curie Industry-Academia Partnerships and Pathways (IAPP, SARM, |EU324509) and Horizon 2020 innovation programme (WIDENLIFE, 692065), Academy of Finland and the Sigrid Juselius Foundation.

Population-Based Study of Prediagnostic Antibodies to Chlamydia trachomatis in Relation to Adverse Pregnancy Outcome.

Chlamydia trachomatis infection is one of the most common sexually transmitted reported bacterial infections worldwide. The well-known sequelae of chlamydial infection include pelvic inflammatory disease and tubal factor infertility, but the evidence linking C. trachomatis infection and adverse pregnancy outcome is inconsistent and has been largely based on case-control studies with limited study populations. We evaluated this link in a population-based longitudinal biobank health registry setting. The association between C. trachomatis major outer membrane protein (MOMP) peptide-specific IgG antibodies and ectopic pregnancy, miscarriage, and preterm delivery was examined in a prospective case-control study nested in the Finnish Maternity Cohort. Ectopic pregnancy and miscarriage cases were identified through the Hospital Discharge Register 1998-2005; cases with preterm deliveries were identified through the Finnish Medical Birth register 1988-2005. Control samples were retrieved from the Finnish Maternity Cohort serum bank. A total of 800 cases of ectopic pregnancy, 800 cases of miscarriage, and 1350 cases of preterm birth were included. Equal number of pregnant women without the outcome diagnosis served as controls. The cases and controls were matched by sampling time, at the serum sampling and postal code district. Antichlamydial IgG antibodies were associated with ectopic pregnancy. Positive antibody levels were found in 21.0% of cases and 14.6% of controls (P = 0.001; odds ratio, 1.56; 95% confidence interval, 1.20-2.03). Previous exposure to C. trachomatis, as indicated by serum antibodies, doubled the risk of ectopic pregnancy within age and was highest among women 35 years or older. Antichlamydial IgG antibody rates between the cases with miscarriage (16.3% in cases vs. 16.8% in controls) or preterm delivery (18.1% vs. 18.1%) and controls did not differ. Our findings confirm the association between previous exposure to C. trachomatis and ectopic pregnancy. We found no association between C. trachomatis seropositivity and miscarriage or preterm birth.

Abstract B45: Seroprevalence of H. pylori in Puerto Rico

Abstract Background: Gastric cancer (GC) is the 4th most common incident cancer and the 2nd leading cause of cancer death worldwide. Approximately 990,000 people are diagnosed with GC worldwide, of whom close to 75% die from this disease. Despite the overall decrease in the global incidence of GC since the 1930s, GC disease is one of the top ten most diagnosed cancers and leading cause of cancer death in Puerto Rico. Risk factors for the development of gastric cancer include: male sex, older age, Helicobacter pylori status, tobacco smoking, diet, living in places with high altitude, low socioeconomic status, and being part of the Asian, Hispanic, and African American communities. However, the prevalence of H. pylori, one of the main risk factors for GC, is unknown in the Puerto Rican Hispanic population. Prevalence of H. pylori infection is influenced by socioeconomic, demographic, and ethnic factors. Thus, this study aimed to determine the seroprevalence and associated risk factors for H. pylori infection among a sub-sample of Puerto Rican Hispanics. Methods: A cross sectional study was designed using an existing population-based biobank that comprised of 1,645 serum samples collected in the parent study “Epidemiology of hepatitis C in the household population of Puerto Rico”. The Premier™ H. pylori enzyme immunoassay (Meridian Bioscience, Inc.) was used to determine the seroprevalence according to the manufacturer's specifications. A prevalence estimate of H. pylori was estimated using logistic regression models according to sociodemographic characteristics. Differences between groups according to H. pylori status were assessed using Student's t-test or Mann-Whitney test for continuous variables, and χ² test or Fisher's exact test, when appropriate, for categorical variables. Multivariable logistic regression models were fitted to estimate the prevalence ratio (PR) with 95% CIs for H. pylori seropositivity. All data was analyzed using Stata for Windows release 13.0 (Stata Corporation, College Station, Texas, USA). Results: A total of 528 representative serum samples (by age, gender, population density, and years of education) from the 1654 were analyzed. The majority of participants were females (55.3%), aged 30-49 years (50.2%), born in PR (89.6%), had ≥ 12 years of education (76.3%), had an annual family income < $20,000 (64.1%), and had health insurance (88.8%). The overall seroprevalence of H. pylori was 35.2% (95% CI=31.2-39.5; females 54.8%). Statistically significant differences in terms of age, place of birth, marital status, years of education, annual family income, type of health insurance, place of residence, and population density were observed when comparing individuals with seropositive to H. pylori and individuals without (p<0.05). Seroprevalence of H. pylori increased according to age-strata; where those ages 30-49 had prevalence of 1.49 (95% CI 1.01-2.18), while those ages 50-64 had higher prevalence of 2.28 (95% CI 1.57-3.33). Individuals born in Puerto Rico had higher seropositive prevalence of H. pylori, compared to individuals not born on the island (PR=2.29; 95% CI=1.24-4.20). The prevalence of H. pylori among individuals living in high-density population areas was higher than those living in low-density areas (PR=0.71, 95% CI=0.56-0.90, p-value=0.005). Conclusions: This is the first report of the seroprevalence of H. pylori in the Puerto Rican Hispanic population. The observed prevalence of H. pylori in Puerto Rican Hispanics is lower than rates reported for US Hispanics and similar to US non-Hispanics. The lower prevalence of H. pylori among individuals living in high-density population areas may be a surrogate for wealth and/or environmental exposures. In summary, the observed health disparities among the Puerto Rican population with regards to H. pylori seroprevalence may impact the incidence of gastric neoplasia and warrant further investigation. Citation Format: Maria del Mar Gonzalez-Pons, Marievelisse Soto-Salgado, Javier Sevilla, Erick L. Suarez, Cynthia M. Perez, Juan M. Marquez-Lespier, Marcia Cruz-Correa. Seroprevalence of H. pylori in Puerto Rico. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B45.

Biobanking in Estonia.

Estonia is a democratic, parliamentary republic with a health care system that is built on the principle of compulsory, solidarity-based insurance and the all-round availability of services of private service providers. Estonia has specific biobank legislation as well as oversight via data protection laws. Its population-based biobank, the Estonian Genome Center (EGCUT), established in 2001, is one of the largest biobanks in Europe, and its database may be used only for scientific research, public health research, and statistics. The EGCUT can issue data to a third party, but only in coded form. This comprehensive database of genotypic, phenotypic, health, and genealogical information represents about 5% of Estonia's adult population, and is the largest cohort ever gathered in Estonia. Government approval is required for international data sharing, and sharing can be further limited by the requirement of ethics approval and permission from Estonian government.

Privacy Laws and Biobanking in Germany.

While the possibility of enacting a sui generis Biobank Act has been debated in Germany at great length, as of yet the country has not implemented any biobankspecific legislation. Instead, oversight is available via a network of research and privacy laws, including those of the European Union. The Nationale Kohorte, Germany's large-scale, population-based epidemiological research biobank, is funded by the Federal Ministry of Education and Research, and there are currently 108 registered bio-banks throughout Germany. The current system, including the structure and study design of the Nationale Kohorte, privileges the protection of personal information even at the cost of socially desirable research; it remains to be seen if forthcoming legislation will shift this balance.

Biobanks in Oral Health: Promises and Implications of Post-Neoliberal Science and Innovation.

While biobanks are established explicitly as scientific infrastructures, they are de facto political-economic ones too. Many biobanks, particularly population-based biobanks, are framed under the rubric of the bio-economy as national political-economic assets that benefit domestic business, while national populations are framed as a natural resource whose genomics, proteomics, and related biological material and national health data can be exploited. We outline how many biobanks epitomize this 'neoliberal' form of science and innovation in which research is driven by market priorities (e.g., profit, shareholder value) underpinned by state or government policies. As both scientific and political-economic infrastructures, biobanks end up entangled in an array of problems associated with market-driven science and innovation. These include: profit trumping other considerations; rentiership trumping entrepreneurship; and applied research trumping basic research. As a result, there has been a push behind new forms of 'post-neoliberal' science and innovation strategies based on principles of openness and collaboration, especially in relation to biobanks. The proliferation of biobanks and the putative transition in both scientific practice and political economy from neoliberalism to post-neoliberalism demands fresh social scientific analyses, particularly as biobanks become further established in fields such as oral health and personalized dentistry. To the best of our knowledge, this is the first analysis of biobanks with a view to what we can anticipate from biobanks and distributed post-genomics global science in the current era of oral health biomarkers.

CMTR1 is associated with increased asthma exacerbations in patients taking inhaled corticosteroids.

Inhaled corticosteroids (ICS) are the most effective controller medications for asthma, and variability in ICS response is associated with genetic variation. Despite ICS treatment, some patients with poor asthma control experience severe asthma exacerbations, defined as a hospitalization or emergency room visit. We hypothesized that some individuals may be at increased risk of asthma exacerbations, despite ICS use, due to genetic factors. A GWAS of 237,726 common, independent markers was conducted in 806 Caucasian asthmatic patients from two population-based biobanks: BioVU, at Vanderbilt University Medical Center (VUMC) in Tennessee (369 patients), and Personalized Medicine Research Project (PMRP) at the Marshfield Clinic in Wisconsin (437 patients). Using a case-control study design, the association of each SNP locus with the outcome of asthma exacerbations (defined as asthma-related emergency department visits or hospitalizations concurrent with oral corticosteroid use), was evaluated for each population by logistic regression analysis, adjusting for age, gender and the first four principal components. A meta-analysis of the results was conducted. Validation of expression of selected candidate genes was determined by evaluating an independent microarray expression data set. Our study identified six novel SNPs associated with differential risk of asthma exacerbations (P < 10(-05)). The top GWAS result, rs2395672 in CMTR1, was associated with an increased risk of exacerbations in both populations (OR = 1.07, 95% CI 1.03-1.11; joint P = 2.3 × 10(-06)). Two SNPs (rs2395672 and rs279728) were associated with increased risk of exacerbations, while the remaining four SNPs (rs4271056, rs6467778, rs2691529, and rs9303988) were associated with decreased risk. Three SNPs (rs2395672, rs6467778, and rs2691529) were present in three genes: CMTR1, TRIM24 and MAGI2. The CMTR1 mRNA transcript was significantly differentially expressed in nasal lavage samples from asthmatics during acute exacerbations, suggesting potential involvement of this gene in the development of this phenotype. We show that genetic variability may contribute to asthma exacerbations in patients taking ICS. Furthermore, our studies implicate CMTR1 as a novel candidate gene with potential roles in the pathogenesis of asthma exacerbations.

Linking a population biobank with national health registries-the estonian experience.

The Estonian population-based biobank, with 52,000 participants’ genetic and health data, is the largest epidemiological cohort in the Baltic region. Participants were recruited through a network of medical professionals throughout Estonia (population 1.34 million). Unique legislation as well as a broad consent form give the Estonian Genome Center, a research institute of the University of Tartu, permission to re-contact participants and to retrieve participants’ data from national registries and databases. In addition to two re-contacting projects to update the health data of participants, extensive clinical characterizations have been retrieved from national registries and hospital databases regularly since 2010. Acquiring data from electronic health records and registries has provided a means to update and enhance the database of the Genome Center in a timely manner and at low cost. The resulting database allows a wide spectrum of genomic and epidemiological research to be conducted with the aim of benefitting public health. Future plans include linking the genome center database with the national health information system through X-road and exchanging data in real time, as well as using the genetic data and the technical infrastructure available for piloting personalized medicine in Estonia.

Massively expedited genome-wide heritability analysis (MEGHA)

The discovery and prioritization of heritable phenotypes is a computational challenge in a variety of settings, including neuroimaging genetics and analyses of the vast phenotypic repositories in electronic health record systems and population-based biobanks. Classical estimates of heritability require twin or pedigree data, which can be costly and difficult to acquire. Genome-wide complex trait analysis is an alternative tool to compute heritability estimates from unrelated individuals, using genome-wide data that are increasingly ubiquitous, but is computationally demanding and becomes difficult to apply in evaluating very large numbers of phenotypes. Here we present a fast and accurate statistical method for high-dimensional heritability analysis using genome-wide SNP data from unrelated individuals, termed massively expedited genome-wide heritability analysis (MEGHA) and accompanying nonparametric sampling techniques that enable flexible inferences for arbitrary statistics of interest. MEGHA produces estimates and significance measures of heritability with several orders of magnitude less computational time than existing methods, making heritability-based prioritization of millions of phenotypes based on data from unrelated individuals tractable for the first time to our knowledge. As a demonstration of application, we conducted heritability analyses on global and local morphometric measurements derived from brain structural MRI scans, using genome-wide SNP data from 1,320 unrelated young healthy adults of non-Hispanic European ancestry. We also computed surface maps of heritability for cortical thickness measures and empirically localized cortical regions where thickness measures were significantly heritable. Our analyses demonstrate the unique capability of MEGHA for large-scale heritability-based screening and high-dimensional heritability profile construction.

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. Initiated in 2010, the Danish Blood Donor Study is a population-based study and biobank. We performed multivariable linear regression analysis to assess the effects of donation activity, physiologic and lifestyle factors, and diet on Hb levels among 15,197 donors. We also performed multivariable logistic regression to evaluate the effects of these factors on the risk of having low Hb (defined as Hb below the 10th percentile among men and women, respectively) and of a decrease in Hb greater than 0.5mmol/L (0.8g/dL) between successive donations. All analyses were performed stratified for sex and smoking status. We also tested a previously used model for the prediction of Hb. The strongest predictors of Hb and risk of low Hb were low ferritin (<15ng/mL) and current use of iron supplementation (yes/no). No dietary factors were found to be consistently significant in multivariable models predicting Hb levels, risk of having low Hb, or risk of a decrease in Hb greater than 0.5mmol/L. We found similar effects to previous studies of factors in the predictive model, with little additional effect of including smoking status and ferritin. As ferritin was the strongest predictor of Hb, this study supports the implementation of regular ferritin measurement as a method of risk assessment among blood donors.

Establishment of a network-based intra-hospital virtual cancer biobank.

There is a growing interest in integrating biomaterial repositories into larger infrastructures in order to meet research demands. However, even for a single hospital or institute, where both population-based and multiple disease-based biobanks have existed for a long time, the integration of existing separate biobanks into a virtual cancer biobank is still challenging. The guidelines and procedures for biobanking are varied and not universally enforced or followed in separate biobanks. Within the last 2 years, we initiated a project to establish a centralized biobank facility in a common storage environment. Analyzing the challenges and interests of stakeholders for the biobanks, a working group comprised of representatives from the central and separate banks, ethic committees, and research administration offices reached an agreement to implement a central facility by following the ISBER best practices for biobanking, and including regular project reviews by the ethical and scientific boards. Furthermore, by implementing a modified minimum information system with biobank data sharing, a network based intra-hospital virtual cancer bank was established to facilitate sharing information of samples held by separate banks. Meanwhile, this virtual biobank network, which has integrated patient information from hospital health care systems, will gradually integrate follow-up information from the cancer registry office and data from epidemiology studies, providing controlled access for sample providers and resource users. In the future, this infrastructure designed for a single hospital may be helpful for building a broader virtual network for data and specimen exchanges.

Human Bio banking as a Team and a Networking project

In medical research, human bio banking is directed to investigate the genetic, molecular and environmental factors underlying diseases. Population-based bio banking of blood from healthy individuals in large epidemiological cohorts and of biological fluids and tissue specimens both in healthy as well as in diseased subjects constitutes the core of biobanks. Population-based biobanks usually explore germline biological traits, whereas biobanks of specimens from diseased subjects aimed to investigate somatic alterations associated to different types of diseases. More in detail, several types of Bio banks exist: 1) Population bio banks, aimed to obtain biomarkers of identity and susceptibility, usually based on the DNA of a large cohort of healthy donor subjects, representative of an ethnic cohort; 2) Disease-oriented bio banks for epidemiology, based on a large sample number, aimed to identify biomarker exposure, usually following a healthy exposed cohort/case-control design. These biobanks study germline DNA or serum markers on the basis of large amounts of specifically designed and collected data; 3) Disease-oriented biobanks (usually tumor banks) aimed to identify disease biomarkers in a collections of samples and their derivates (DNA/RNA/proteins), usually associated to clinical data and / or clinical trials. The amount of clinical data linked to the sample determinates the availability and biological value of the sample. Biobank organization is a complex tool involving logistic infrastructures as well as specifically developed informatics tools and ethical issues.

Integration, Networking, and Global Biobanking in the Age of New Biology.

Scientific revolution is changing the world forever. Many new disciplines and fields have emerged with unlimited possibilities and opportunities. Biobanking is one of many that is benefiting from revolutionary milestones in human genome, post-genomic, and computer and bioinformatics discoveries. The storage, management, and analysis of massive clinical and biological data sets cannot be achieved without a global collaboration and networking. At the same time, biobanking is facing many significant challenges that need to be addressed and solved including dealing with an ever increasing complexity of sample storage and retrieval, data management and integration, and establishing common platforms in a global context. The overall picture of the biobanking of the future, however, is promising. Many population-based biobanks have been formed, and more are under development. It is certain that amazing discoveries will emerge from this large-scale method of preserving and accessing human samples. Signs of a healthy collaboration between industry, academy, and government are encouraging.

Cohort Profile: LifeLines, a three-generation cohort study and biobank.

The LifeLines Cohort Study is a large population-based cohort study and biobank that was established as a resource for research on complex interactions between environmental, phenotypic and genomic factors in the development of chronic diseases and healthy ageing. Between 2006 and 2013, inhabitants of the northern part of The Netherlands and their families were invited to participate, thereby contributing to a three-generation design. Participants visited one of the LifeLines research sites for a physical examination, including lung function, ECG and cognition tests, and completed extensive questionnaires. Baseline data were collected for 167 729 participants, aged from 6 months to 93 years. Follow-up visits are scheduled every 5 years, and in between participants receive follow-up questionnaires. Linkage is being established with medical registries and environmental data. LifeLines contains information on biochemistry, medical history, psychosocial characteristics, lifestyle and more. Genomic data are available including genome-wide genetic data of 15 638 participants. Fasting blood and 24-h urine samples are processed on the day of collection and stored at -80 °C in a fully automated storage facility. The aim of LifeLines is to be a resource for the national and international scientific community. Requests for data and biomaterials can be submitted to the LifeLines Research Office [LLscience@umcg.nl].