DBDS Genomic Cohort, a prospective and comprehensive resource for integrative and temporal analysis of genetic, environmental and lifestyle factors affecting health of blood donors

Abstract

Purpose: To establish a cohort that enables identification of genomic factors that influence human health and empower increased blood donor health and safe blood transfusions. Human health is complex and involves several factors, a major one being the genomic aspect. The genomic era has resulted in many consortia encompassing large samples sizes, which has proven successful for identifying genetic factors associated with specific traits. However, it remains a big challenge to establish large cohorts that facilitate studies of the interaction between genetic factors, environmental and life-style factors as these change over the course of life. A major obstacle to such endeavours is that it is difficult to revisit participants to retrieve additional information and obtain longitudinal, consecutive measurements.

Participants: Blood donors (n=110 000) have given consent to participate in the Danish Blood Donor Study. The study uses the infrastructure of the Danish blood banks.

Findings to date: The cohort comprises extensive phenotype data and whole genome genotyping data. Further, it is possible to retrieve additional phenotype data from national registries as well as from the donors at future visits, including consecutive measurements.

Future plans: To provide new knowledge on factors influencing our health and thus provide a platform for studying the influence of genomic factors on human health, in particular the interaction between environmental and genetic factors.

Keywords: genetics; preventive medicine; public health.

Figure 1

Relationships for DBDS donors genotyped as part of the first batch(n=85 000). Each point represents a pair of related individuals and the colours indicate the degree of relatedness (‘InfType’ in KING IBD segment inference): monozygotic twins and technical duplicates (MZ/DUP) in pink (in the upper left corner), first degree relatives as parent-offspring pairs (PO, dark green) and full siblings (FS, light green), second and third degree relatives in dark and light purple, respectively. The y-axis shows the estimated kinship coefficient, defined as the probability that two alleles sampled at random (one from each individual) are identical by descent. The x-axis shows the proportion of zero identity-by-state (IBS0), defined as the proportion of SNPs at which two samples share no alleles. KING’s criteria were used to estimate the degree of relatedness (--related command in KING). We used a set of independent high-quality markers (excluding palindromic and non-autosomal markers, markers with MAF<1%, low call-rate (<99%) and markers in regions with high Linkage Disequilibrium) for the relatedness calculation. DBDS, The Danish Blood Donor Study; MAF, minor allele frequency.

Figure 2

MAF distribution of the genotyped SNPs prior to quality control. DBDS, The Danish Blood Donor Study; MAF, minor allele frequency; SNP, single nucleotide polymorphism.