Background Familial Hypercholesterolemia (FH) is an autosomal-dominant disorder caused by mutations in one of three genes. In the 60% of patients who are mutation-negative we have recently shown that the clinical phenotype can be associated with an accumulation of common small-effect LDL-C-raising alleles using a 12-SNP score. The aims of the study were to improve the selection of SNPs, and to replicate the results in additional samples. Methods Receiver-operating characteristic curves were used to determine the optimum number of LDL-C SNPs. For replication analysis, we genotyped patients with a clinical diagnosis of FH from six countries for six LDL-C-associated alleles. We compared the weighted SNP score among patients with no confirmed mutation (FH/M-), those with a mutation (FH/M+), and controls from an UK population sample (WHII). Results Increasing the number of SNPs to 33 did not improve the ability of the score to discriminate between FH/M- and controls, while sequential removal of SNPs with smaller effects/lower frequency showed a weighted score of six SNPs performed as well as the 12-SNP score. Meta-analysis of the weighted 6-SNP score, based on polymorphisms in CELSR2, APOB, ABCG5/8, LDLR and APOE loci, in the independent FH/M- cohorts showed a consistently higher score in comparison to the WHII population (P<2.2×10-16). Modeling in individuals with a 6-SNP score in the top three quarters of the score distribution, indicated a >95% likelihood of a polygenic explanation of their increased LDL-C. Conclusion A 6-SNP LDL-C score consistently distinguishes FH/M- patients from healthy subjects. The hypercholesterolemia in 88% of mutation-negative patients is likely to have a polygenic basis.

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Toll-like receptors (TLRs) and myeloid differentiation primary response protein 88 (MYD88) gene polymorphisms may be involved in the pathogenesis of Hodgkin's lymphoma (HL) through altered immunoregulatory and inflammatory responses. A candidate-gene association study was conducted to investigate the association between TLR9 À1237T4C, TLR9 2848A4G, MYD88 À938C4A and MYD88 1944C4G gene polymorphisms and the risk for HL. The impact of haplotypes was also examined. The study showed that carriership for À1237C and 2848A was associated with an increased risk for HL (odds ratio (OR)¼2.53 (1.36-4.71) and OR¼6.20 (1.3-28.8)). The MYD88 polymorphisms produced nonsignificant results. The estimated frequencies of the TLR9/1237C-2848A and MYD88/938C-1944G haplotypes were also significantly different between HL and controls (Po0.01). In addition, a significant difference between HL and controls was observed for the TLR9/1237C-TLR9/ 2848A-MYD88/938C-MYD88/1944C haplotypes (Po0.01). In conclusion, our study showed that TLR polymorphisms, and TLR9 and MYD88 haplotypes are related to the development of HL.

Direct-to-consumer genetic testing (DTCGT) is now offered by numerous companies. The present survey aimed to explore awareness, interest, reasons to take and refuse DTCGT, and understanding of results amongst 725 higher education students in Greece. A third of the responders were aware of DTCGT and interest was dependent on cost. More than 60% of the participants would undergo DTCGT to learn more about their health, to warn their children, so that their doctor can monitor their health and change their lifestyle. Nevertheless, they would prefer to consult their doctor first and expressed concerned about their personal data. After receiving results from a hypothetical DTC genetic test predicting higher risk for colon cancer, 59.5% of the responders thought that they could understand the results but 46.1% believed that the results have diagnostic value. In total, 83.6% of the participants would ask their doctor to explain the results and 70.4% would discuss results with their family. In conclusion, the majority of higher education students in Greece appreciate the benefits of genetic testing but with the involvement of their doctor. A physician's participation in the process and informing the public about the true value of genetic testing, are crucial to avoid misinterpretation of DTCGT results.

Organoids hold great promises for numerous applications in biomedicine and biotechnology. Despite its potential in science, organoid technology poses complex ethical challenges that may hinder any future benefits for patients and society. This study aims to analyze the multifaceted ethical issues raised by organoids and recommend measures that must be taken at various levels to ensure the ethical use and application of this technology. Organoid technology raises several serious ethics issues related to the source of stem cells for organoid creation, informed consent and privacy of cell donors, the moral and legal status of organoids, the potential acquisition of human “characteristics or qualities”, use of gene editing, creation of chimeras, organoid transplantation, commercialization and patentability, issues of equity in the resulting treatments, potential misuse and dual use issues and long-term storage in biobanks. Existing guidelines and regulatory frameworks that are applicable to organoids are also discussed. It is concluded that despite the serious ethical challenges posed by organoid use and biobanking, we have a moral obligation to support organoid research and ensure that we do not lose any of the potential benefits that organoids offer. In this direction, a four-step approach is recommended, which includes existing regulations and guidelines, special regulatory provisions that may be needed, public engagement and continuous monitoring of the rapid advancements in the field. This approach may help maximize the biomedical and social benefits of organoid technology and contribute to future governance models in organoid technology.