Genomic insights into abdominal aortic aneurysms

Introduction

An individual’s genetic background plays a significant role in his or her chances of developing an abdominal aortic aneurysm (AAA). This risk is likely to be due to a combination of multiple small effect genetic factors acting together, resulting in considerable difficulty in the identification of these factors.

Methods

Methods for the identification of genetic factors associated with disease are usually based on the analysis of genetic variants in case-control studies. Over the last decade, owing to advances in bioinformatics and laboratory technology, these studies have progressed from focusing on the examination of a single genetic variant in each study to the examination of many millions of variants in a single experiment. We have conducted a series of such experiments using these methods.

Results

Our original methods using candidate gene approaches led to the initial identification of a genetic variant in the interleukin-10 gene associated with AAA. However, further studies failed to confirm this association and highlighted the necessity for adequately powered studies to be conducted, as well as the need for confirmatory studies to be performed, prior to the acceptance of a variant as a risk for disease. The subsequent application of genomic techniques to our sample set, in a global collaboration, has led to the identification of three robustly verified risk loci for AAA in the LRP1, LDLR and SORT1 genes.

Conclusions

Genomic studies of AAA have led to the identification of new pathways involved in the pathogenesis of AAA. The exploration of these pathways has the potential to unlock new avenues for therapeutic intervention to prevent the development and progression of AAA.     

Reconciling Opportunistic and Population Screening in Clinical Genomics

Opportunistic genomic screening is becoming increasingly common as laboratories adopt recommendations to report secondary genomic findings. In parallel, interest in using genome sequencing as a population screening test has grown rapidly. We consider here 3 potential applications of genome sequencing for preventive medicine: (1) provider-ordered predispositional testing in healthy adults, (2) indication-based testing with opportunistic screening of secondary results, and (3) population screening in the public health context. We conclude that despite superficial similarities, there are important and fundamental differences in the way medical risks and benefits can be addressed in these 3 contexts. Recommendations to report secondary genomic findings should not be interpreted as an endorsement of population genomic screening. Ongoing work is developing the evidence that will be needed to fully justify current and future initiatives in population genomic screening. Ongoing work is developing the evidence that will be needed to fully justify current and future initiatives in population genomic screening.     

Pathogenomics insights for understanding Pasteurella multocida adaptation

Pasteurella multocida is an important veterinary pathogen able to infect a wide range of animals in a broad spectrum of diseases. P. multocida is a complex microorganism in relation to its genomic flexibility, host adaptation and pathogenesis. Epidemiological analysis based on multilocus sequence typing, serotyping, genotyping, association with virulence genes and single nucleotide polymorphisms (SNPs), enables assessment of intraspecies diversity, phylogenetic and strain-specific relationships associated with host predilection or disease. A high number of sequenced genomes provides us a more accurate genomic and epidemiological interpretation to determine whether certain lineages can infect a host or produce disease. Comparative genomic analysis and pan-genomic approaches have revealed a flexible genome for hosting mobile genetic elements (MGEs) and therefore significant variation in gene content. Moreover, it was possible to find lineage-specific MGEs from the same niche, showing acquisition probably due to an evolutionary convergence event or to a genetic group with infective capacity. Furthermore, diversification selection analysis exhibits proteins exposed on the surface subject to selection pressures with an interstrain heterogeneity related to their ability to adapt. This article is the first review describing the genomic relationship to elucidate the diversity and evolution of P. multocida.     

Experts reflecting on the duty to recontact patients and research participants; why professionals should take the lead in developing guidelines

Sequencing technology is increasing the scale of information that could benefit patients who have been tested in the past. This raises the question whether professionals have a duty to recontact such patients or their families. There is currently no clear basis for a legal duty to recontact, and professional guidelines are limited. We conducted interviews with 14 senior professionals from the Netherlands and UK to obtain a range of opinions on what obligations are estimated to be possible or desirable. There was (near) consensus that a lack of resources currently inhibits recontacting in clinical practice, that recontacting is less desirable in research, that information on recontacting should be part of informed consent, and that a legal duty should follow professional standards. There was a diversity of opinions on the desirability of a more systematic approach, potential obligations in hybrid clinical-research projects, and who should bear responsibility for seeking updates. Based on the literature, legal framework and these interviews, we conclude that a general duty to recontact is unlikely, but that in specific circumstances a limited duty may apply if the benefit to the individual is significant and the burden on professionals not too extensive. The variation in opinion demonstrates that further deliberations are desirable. The development of guidelines—a process the European Society of Human Genetics has begun—is important to ensure that the courts, in deciding a recontacting case, can take into account what professionals consider responsible standards in this field.     

抗磷脂抗体和子痫前期的研究进展

抗磷脂抗体是一类能与磷脂或磷脂结合蛋白结合的自身免疫性抗体,与血栓形成、不良孕产史密切相关。抗磷脂抗体中高滴度阳性的患者易有子痫前期等不良妊娠结局。子痫前期发生于妊娠期,可导致全身多脏器的损伤,严重危及母儿生命和健康。子痫前期的发病机制目前还不是很清楚,研究提示抗磷脂抗体可能通过诱导氧化应激,促进血管内炎症等作用参与子痫前期的发病;对于抗磷脂抗体阳性的患者,早期发现和早期干预对获得良好的妊娠结局至关重要。     

Precision health: A nursing perspective

Precision health refers to personalized healthcare based on a person’s unique genetic, genomic, or omic composition within the context of lifestyle, social, economic, cultural and environmental influences to help individuals achieve well-being and optimal health. Precision health utilizes big data sets that combine omics (i.e. genomic sequence, protein, metabolite, and microbiome information) with clinical information and health outcomes to optimize disease diagnosis, treatment and prevention specific to each patient. Successful implementation of precision health requires interprofessional collaboration, community outreach efforts, and coordination of care, a mission that nurses are well-positioned to lead. Despite the surge of interest and attention to precision health, most nurses are not well-versed in precision health or its implications for the nursing profession. Based on a critical analysis of literature and expert opinions, this paper provides an overview of precision health and the importance of engaging the nursing profession for its implementation. Other topics reviewed in this paper include big data and omics, information science, integration of family health history in precision health, and nursing omics research in symptom science. The paper concludes with recommendations for nurse leaders in research, education, clinical practice, nursing administration and policy settings for which to develop strategic plans to implement precision health.