Study Design and Interim Outcomes of Guangzhou Institute of Respiratory Disease COPD Biobank

Background: GIRD COPD Biobank is a multicenter observational study blood-based database with local characteristics, in order to investigate the causes, risk factors, pathogenesis, prevalence patterns and trends of COPD and promote new pathogenic insights in China.

Methods: We enrolled 855 clinically COPD patients and 660 controls with normal lung function. Extensive data collection has been undertaken with questionnaires, clinical measurements, and collection and storage of blood specimens, following Standard Operating Procedures (SOP). All surveys had similar quality controls, supervisions, and training of the investigator team.

Results: Since September 2010, a total of 1515 subjects (1116 [73.7%] males; 855 [56.4%] diagnosed with COPD) were enrolled. Analyses of the design and interim results of the GIRD COPD Biobank Study identified patients with COPD were older, lower educational level, a longer history of pack-year smoking, less in kitchen fan usage, X-ray exposure, and history of disease (P < 0.01 for all); Most of the COPD subjects belonged to moderately severe or worse, stratified according to Global Lung Function Initiative (GLI); COPD patients had relatively more co-morbidities than controls; Environmental hazard exposures might be the main contributors to the reported respiratory symptoms; Cold air, haze, and influenza acted the top three factors to induce respiratory symptoms in both COPD cases and controls.

Conclusion: The GIRD COPD Biobank Study has the potential to provide substantial novel insights into the genetics, biomarkers, environmental and lifestyle aspects of COPD. It is expected to provide new insights for pathogenesis and the long-term progression of COPD.     

Broad consent versus dynamic consent in biobank research: Is passive participation an ethical problem?

In the endeavour of biobank research there is dispute concerning what type of consent and which form of donor–biobank relationship meet high ethical standards. Up until now, a ‘broad consent'' model has been used in many present-day biobank projects. However it has been, by some scholars, deemed as a pragmatic, and not an acceptable ethical solution. Calls for change have been made on the basis of avoidance of paternalism, intentions to fulfil the principle of autonomy, wish for increased user participation, a questioning of the role of experts and ideas advocating reduction of top–down governance. Recently, an approach termed ‘dynamic consent'' has been proposed to meet such challenges. Dynamic consent uses modern communication strategies to inform, involve, offer choices and last but not the least obtain consent for every research projects based on biobank resources. At first glance dynamic consent seems appealing, and we have identified six claims of superiority of this model; claims pertaining to autonomy, information, increased engagement, control, social robustness and reciprocity. However, after closer examination, there seems to be several weaknesses with a dynamic consent approach; among others the risk of inviting people into the therapeutic misconception as well as individualizing the ethical review of research projects. When comparing the two models, broad consent still holds and can be deemed a good ethical solution for longitudinal biobank research. Nevertheless, there is potential for improvement in the broad model, and criticism can be met by adapting some of the modern communication strategies proposed in the dynamic consent approach.     

Efficient identification of trait-associated loss-of-function variants in the UK Biobank cohort by exome-sequencing based genotype imputation

The large-scale open access whole-exome sequencing (WES) data of the UK Biobank ~200,000 participants is accelerating a new wave of genetic association studies aiming to identify rare and functional loss-of-function (LoF) variants associated with complex traits and diseases. We proposed to merge the WES genotypes and the genome-wide genotyping (GWAS) genotypes of 167,000 UKB homogeneous European participants into a combined reference panel, and then to impute 241,911 UKB homogeneous European participants who had the GWAS genotypes only. We then used the imputed data to replicate association identified in the discovery WES sample. The average imputation accuracy measure r² is modest to high for LoF variants at all minor allele frequency intervals: 0.942 at MAF interval (0.01, 0.5), 0.807 at (1.0 × 10⁻³, 0.01), 0.805 at (1.0 × 10⁻⁴, 1.0 × 10⁻³), 0.664 at (1.0 × 10⁻⁵, 1.0 × 10⁻⁴) and 0.410 at (0, 1.0 × 10⁻⁵). As applications, we studied associations of LoF variants with estimated heel BMD and four lipid traits. In addition to replicating dozens of previously reported genes, we also identified three novel associations, two genes PLIN1 and ANGPTL3 for high-density-lipoprotein cholesterol and one gene PDE3B for triglycerides. Our results highlighted the strength of WES based genotype imputation as well as provided useful imputed data within the UKB cohort.     

Contributing to research via biobanks: what it means to cancer patients

Context and objective Biobanks have become strategic resources for biomedical and genetic research. The aim of the present empirical qualitative study was to investigate how patients with cancer perceive and experience the process of donation to biobanks, focussing on the subjective meanings associated with their decisions when they are asked in a routine context to agree to their own biological specimens being used for research projects. Design A qualitative study, using semi‐structured interviews to explore in depth the reasons why patients with cancer agree to participating in biobanking. Participants Nineteen patients (aged 28–82 years) being treated for colorectal cancer or leukaemia at a French cancer centre participated in this study. Results Contributing to biobanks was experienced here as a rewarding and empowering individual experience because of the psychological issues involved, such as feelings of hope associated with research, because it makes the relationship with researchers and clinicians less asymmetrical, revalorization of otherwise ‘wasted’ tissue, and also as an act of solidarity and reciprocity, which makes patients part of a community. Discussion and conclusion Patients seem to regard contributing to biobanks as an act of benevolence, which they are motivated to perform because of societal welfare considerations as well as the hope of subjective benefits. Knowledge about the patients’ perspective and of the psychological rewards associated with tumour donation should be taken into account by physicians and caregivers discussing this topic with their patients.     

Joint Nordic prospective study on human herpesvirus 8 and multiple myeloma risk

An association between human herpesvirus 8 (HHV8) and multiple myeloma (MM) has been reported, though most studies have not confirmed such association. To follow-up on a previous prospective seroepidemiological study, where HHV8 tended to associate with MM risk, we linked five large serum banks in the Nordic countries with the Nordic cancer registries and 329 prospectively occurring cases of MM were identified, together with 1631 control subjects matched by age and gender. The HHV8 seroprevalences among cases and controls were similar (12 and 15%, respectively) and HHV8 seropositivity did not associate with the risk of MM, neither when considering positivity for lytic antibodies (relative risk (RR) = 0.8, 95% confidence interval (CI) = 0.5-1.1) nor for latent antibodies (RR = 0.6, 95% CI = 0.1-2.7). Similar risks were seen when analysis was restricted to case-control sets with at least 2 years lag before diagnosis (RR = 0.8, 95% CI = 0.5-1.2 and RR = 0.9, 95% CI = 0.1-4.2). In conclusion, the data indicate that HHV8 infection is not associated with MM.     

The Right to Withdraw Consent to Research on Biobank Samples

Ethical guidelines commonly state that research subjects should have a right to withdraw consent to participate. According to the guidelines we have studied, this right applies also to research on biological samples. However, research conducted on human subjects themselves differs in important respects from research on biological samples. It is therefore not obvious that the same rights should be granted research participants in the two cases. This paper investigates arguments for and against granting a right to withdraw consent to research on biobank samples. We conclude that (1) there are no explicit arguments for such a right in the guidelines we have studied, (2) the arguments against such a right are inconclusive, (3) considerations of autonomy, privacy, personal integrity, and trust in medical research provide sufficient reasons for granting a right to withdraw consent to research on biobank samples, (4) in certain cases, research participants should be allowed to waive this right.     

Early infections of Toxoplasma gondii and the later development of schizophrenia

Early exposure to several infectious agents has been associated with the later development of schizophrenia. Two recent studies assessed in utero or early postnatal exposure to Toxoplasma gondii. In one study of 63 individuals, who developed schizophrenia spectrum disorders, maternal sera obtained during pregnancy showed an increased risk (OR 2.61) of having IgG antibodies to T. gondii. In the other study of 71 individuals who developed schizophrenia, sera obtained shortly after birth also showed an increased risk (OR 1.79) of having IgG antibodies to T. gondii. Causal linking mechanisms are at present speculative but include possible direct effects of maternal IgG on the developing central nervous system (CNS) of the offspring. Additional studies are underway.