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- Global Survey Of Genetic Testing Methods For Familial Hypercholesterolaemia: A Study And Recommendations From The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration RegistryPublication . Chora, Joana Rita; Karungi, Irene; Elshorbagy, Amany; Stevens, Christophe A.T.; Vallejo-Vaz, Antonio J.; Dharmayat, Kanika I.; Abifadel, Marianne; Aguilar-Salinas, Carlos A.; Alhabib, Khalid F.; Almahmeed, Wael; Alnouri, Fahad; Alonso, Rodrigo; Al-Rasadi, Khalid; Al-Sarraf, Ahmad; Arca, Marcello; Ashaat, Engy A.; Ashavaid, Tester F.; Averna, Maurizio; Banach, Maciej; Becker, Marianne; Binder, Christoph J.; Brunham, Liam R.; Catapano, Alberico L.; Corral, Pablo; Descamps, Olivier S.; Drogari, Euridiki; Durst, Ronen; Ezhov, Marat; Groselj, Urh; Harada-Shiba, Mariko; Holven, Kirsten B.; Hovingh, G. Kees; Khovidhunkit, Weerapan; Lalic, Katarina; Latkovskis, Gustavs; Laufs, Ulrich; Liberopoulos, Evangelos; Lin, Jie; März, Winfried; Mata, Pedro; Matthias, Anne Thushara; Miserez, André R.; Mitchenko, Olena; Nawawi, Hapizah Mohd; Nordestgaard, Børge G.; Panayiotou, Andrie G.; Paragh, György; Petrulioniene, Zaneta; Postadzhiyan, Arman; Reyes, Ximena; Sadiq, Fouzia; Sahebkar, Amirhossein; Santos, Raul D.; Sawhney, J.P.S.; Schunkert, Heribert; Shah, Swarup A.V.; Shek, Aleksandr B.; Soran, Handrean; Su, Ta-Chen; Subramaniam, Tavintharan; Tilney, Myra; Tomlinson, Brian; Truong, Thanh Huong; Tybjærg-Hansen, Anne; Viigimaa, Margus; Vohnout, Branislav; Watts, Gerald F.; Yamashita, Shizuya; Ray, Kausik K.; Raal, Frederick J.; Humphries, Steve E.; Freiberger, Tomas; Bourbon, Mafalda; EAS FHSCBackground and aims: Familial hypercholesterolemia (FH), primarily caused by pathogenic LDLR, APOB, or PCSK9 variants, results in elevated LDL-C and increased cardiovascular risk. Genetic testing offers the definitive diagnosis, yet global approaches to FH genetic testing remain unstandardized. We investigate current testing practices worldwide and provide relevant recommendations. Methods: A survey was distributed to national lead-investigators (NLIs) of 68 countries in the FH-Studies Collaboration, assessing referral criteria, assay methodologies, target genes, and pathogenicity interpretation methods. Results: NLIs from centres in 55/68 countries (81%) responded, spanning Africa (N=2), Americas (N=6), Asia (N=20), Europe (N=26), and Oceania (N=1). DLCN scores were the most common reason for referral to genetic testing (adults:72%; children:57%). Simon Broome and MEDPED criteria were reported only by centres from high-income countries (adults: 7% and 2%; children: 12% and 2%). Methods for testing in index versus non-index cases were significantly different (p <0.001). Next-generation sequencing (NGS) was the predominant assay method for index cases (62%), while Sanger sequencing was favoured for non-index (71%). However, these testing techniques did not differ between centres from high- and non-high-income countries for index cases (p=0.74) and non-index cases (p=0.49). Copy-number variants (CNVs) were assessed by 65% of centres, with most integrating CNV analysis into NGS platforms (86%) and others (14%) using multiplex ligation-dependent probe-amplification (MLPA) or microarrays. Screening encompassed LDLR (100%), APOB (97%), PCSK9 (95%), and other genes. Most centres (96%) incorporated pathogenicity interpretation into their reports, adhering largely to American College of Medical Genetics and Genomics guidelines. Conclusions: FH genetic testing practices vary widely across countries surveyed, emphasizing the need for global standardization to enhance accuracy and comparability of FH diagnoses worldwide. We suggest that genetic testing should include the three FH-causing genes and ideally the five associated/phenocopy genes.
- Data Privacy, Ownership, and Secondary Use of Clinical Data Generated by Continuous Glucose Monitors and Mobile Health Applications: A ReviewPublication . Dario, PauloThe growing use of continuous glucose monitors (CGMs) and mobile health (mHealth) applications has changed how diabetes is managed, allowing real-time tracking of glycemic patterns and remote clinical decision-making. These technologies also generate large volumes of sensitive health data, raising questions about who owns this information, how it is protected, and under what conditions it may be repurposed for research or commercial objectives. This review examines the regulatory frameworks governing CGM and mHealth data in major jurisdictions, with particular attention to the Health Insurance Portability and Accountability Act (HIPAA) in the United States and the General Data Protection Regulation (GDPR) in the European Union. Significant regulatory gaps exist, particularly for consumer-grade devices and direct-to-consumer mHealth applications that fall outside traditional healthcare data-protection frameworks. Data ownership remains legally ambiguous in most jurisdictions, with patients, healthcare providers, device manufacturers, and app developers each holding competing claims. The secondary use of clinical data for research, while it could materially advance diabetes care, raises ethical concerns around informed consent, data de-identification, and the boundaries between clinical care and commercial exploitation. Emerging approaches, including the European Health Data Space, federated learning, and differential privacy, may help balance data utility with individual rights. The review recommends changes to regulation, industry practice, and consent models aimed at reconciling data-driven diabetes research with patient autonomy and privacy.
- A multi-stakeholder perspective on Barriers to the adoption of personalized prevention in European healthcare systemsPublication . Costa, Alexandra; Cardoso, Maria Luís; Carvalho, Adriana Reimão; Osti, Tommaso; Farina, Sara; Taha, Abdelrahman; Savoia, Cosimo; Russo, Luigi; Maio, Alessandra; Scarsi, Nicolò; Flodkvist, Evelina; Gyllenberg, Alexandra; Boccia, Stefania; Vicente, Astrid MouraIntroduction: Personalized prevention is an important component of personalized medicine, tailoring interventions to the biological, behavioral, sociocultural and environmental characteristics of individuals for the prevention of disease onset, progression and recurrence. Despite its potential, personalized preventive interventions (PPI) remain less commonly implemented in clinical practice. This study explored the main barriers to a broader adoption of PPI in European healthcare systems. Methods: A multi-stakeholder consultation involving citizens/patients, health professionals, researchers, and policymakers was conducted using a sequential mixed-methods approach. In the first phase, semi-structured interviews with key informants representing different stakeholder groups were conducted. The thematic analysis of interview findings, complemented by insights from a review of the literature, informed the development of an online survey implemented in the second phase of the study. Twenty-six interviews and 270 complete surveys were analyzed. Stakeholders identified barriers across three main domains: (1) healthcare systems, (2) implementation, and (3) awareness, education, and literacy. Key barriers associated with limited PPI adoption included the predominant focus of health strategies on treatment over prevention, unresolved ethical, legal, and social issues (ELSI), limited awareness and knowledge of personalized prevention among both professionals and citizens, and the lack of appropriate cost–benefit evaluation models. Findings highlight interconnected barriers that may impact a broader PPI adoption across healthcare system, governance, implementation, and awareness-related domains. Continued stakeholder dialogue and engagement, alongside efforts to address awareness and governance-related challenges, may support the broader integration of PPI into European healthcare systems.
- The Spectrum of Genetic Causes of Familial Hypercholesterolemia PhenotypePublication . Bourbon, M.; Alves, A.C.; Chora, J.R.; Hooper, A.J.; Abifadel, M.Purpose of review: This paper reviews the genetic spectrum underlying the Familial Hypercholesterolemia (FH) phenotype, aiming to improve diagnosis, awareness and understanding of these inherited lipid disorders. Recent findings: Although genetic testing for FH has traditionally targeted LDLR, APOB, and PCSK9, the adoption of an expanded eight-gene sequencing panel is now recommended. This broader approach improves diagnostic accuracy by identifying additional lipid disorders that mimic the FH phenotype. Among these, sitosterolemia and the APOE variant p.(Leu167del) appear to be more prevalent than previously recognized. LDLR variants remain the predominant cause of FH, yet the functional significance of approximately half of the reported variants remains undetermined. Recent research efforts are increasing and aimed at resolving these uncertainties through functional characterization studies. Penetrance varies markedly among FH genes, with LDLR variants showing highest penetrance (> 90%), APOB intermediate (~ 50-70%), and PCSK9 is gain-of-function dependent, influencing phenotype severity. Familial hypercholesterolemia (FH) remains widely underdiagnosed and undertreated, increasing preventable cardiovascular risk. Advances in genetic testing with expanded multi-gene panels have enhanced diagnostic precision, but accurate variant classification-using ACMG guidelines and functional assays-is crucial to reduce variants of uncertain significance. Expanded FH genetic testing not only differentiates true FH from phenocopies but also strengthens the individualized management of lipid disorders. By enabling therapy to target the specific affected pathway, it represents an important step toward precision medicine and improved patient outcomes. Data sharing initiatives like PerMedFH further improve variant interpretation and clinical utility.
- A strategic research and innovation Agenda for personalized prevention: towards a European implementation roadmapPublication . Boccia, Stefania; Pastorino, Roberta; PROPHET ConsortiumNo abstract available
- Ancestry-stratified variant classification in monogenic diabetes genes: Annotation coverage and differential curation burdenPublication . Dario, PauloBackground: Variant databases ClinVar and gnomAD underpin clinical variant interpretation, but their composition is skewed toward European ancestry. Whether this produces systematic disadvantages for non-European patients with monogenic diabetes has not been examined at the database level with mutually exclusive ancestry groups. Objective: To quantify ClinVar annotation coverage and ancestry-stratified classification outcomes across monogenic diabetes genes, using mutually exclusive population-private variant groups. Methods: gnomAD v4.0 (genomes and exomes; 807,162 individuals) was cross-referenced with the ClinVar GRCh38 record (accessed June 29, 2026) for 16 monogenic diabetes (maturity-onset diabetes of the young [MODY]) genes, and variants were classified as population-private to European or non-European ancestry from ancestry-specific allele counts. Results: Across 54,865 gnomAD variants, 86.7% carried no ClinVar classification. The annotation gap was near-universal rather than ancestry-specific (unannotated fraction 89.4% European-private, 87.5% non-European-private). Among classified population-private variants, however, the pathogenic or likely pathogenic rate was 19.8% for European-private but only 8.6% for non-European-private variants (Fisher exact OR 2.6, 95% CI 2.1-3.3, p = 1 × 10- 1 8), with a higher uncertain-significance rate in non-European-private variants (52.1% vs. 45.8%). Conclusion: The dominant problem is therefore an annotation deficit affecting all ancestries; the ancestry inequity the data support is one of actionability, not of raw uncertain-significance rates. Closing it requires ClinVar submissions and population-specific sequencing from underrepresented populations.
- Familial Hypercholesterolaemia In Children And Adolescents: A European Atherosclerosis Society Consensus StatementPublication . Wiegman, Albert; Bourbon, Mafalda; Freiberger, Tomas; Gidding, Samuel S; Greber-Platzer, Susanne; Groselj, Urh; Holven, Kirsten B.; Hudgins, Lisa C.; Humphries, Steve E.; Hutten, Barbara A.; Ibarretxe, Daiana; Pederiva, Cristina; Peretti, Noel; Raal, Frederick J.; Ramaswami, Uma; Sanin, Veronika; Santos, Raul D.; Steinhagen-Thiessen, Elisabeth; Watts, Gerald F.; Perkins, Rosie; Benn, Marianne; Binder, Christoph J.; Romeo, Stefano; Lennep, Jeanine E. Roeters vanFamilial hypercholesterolaemia (FH) is a common genetic disorder characterized by lifelong elevated LDL cholesterol (LDL-C) concentrations. FH exists in two forms: heterozygous FH (HeFH), which affects around 1 in 300 people worldwide, and homozygous FH (HoFH), which affects around 1 in 300 000. Individuals with FH are at increased risk of premature atherosclerotic cardiovascular disease (ASCVD) and death, and those with HoFH are, if untreated, at extreme risk of ASCVD manifestations even before adulthood. Early diagnosis and treatment in childhood can extend or normalize life expectancy, but limited awareness, underdiagnosis, and undertreatment remain major challenges. This consensus statement aims to address these challenges, supported by increased knowledge of the pathogenesis of FH and the availability of an increasing range of lipid-lowering therapies (LLTs) that can be used from early ages. To increase the detection rate of FH, all countries are encouraged to establish a paediatric screening programme and, given that current diagnostic criteria often fail to identify children with an FH-causing genetic variant, revised diagnostic criteria are presented. Updated LDL-C treatment goals are proposed, and the importance of starting LLTs before puberty in children with HeFH, and, if needed, from 6 years, is highlighted. Guidance on how to manage FH is provided, including treatment algorithms for use in children with either HeFH or HoFH and a discussion on how to promote a smooth transition to adult care. Early detection and optimal treatment as advocated in this consensus statement are crucial to improving life expectancy for children and adolescents with FH.
- The Role of Immunogenetics in the Host-Parasite Interaction of Chagas Disease: Implications for Personalized MedicinePublication . Hassnain, Muhammad; Bukhari, Syeda Mahnoor; Bibi, Tahira; Waheed, Syeda Fakhra; Botelho, Monica C.; Ahmad, WaqasChagas disease, caused by the protozoan parasite Trypanosoma cruzi, continues to be a significant global health issue, especially in Latin America, with increasing international prevalence due to migration. Despite advancements in diagnosis and treatment, it remains a neglected tropical disease characterized by significant morbidity and mortality, mainly influenced by the complex interaction between parasite diversity and host immune responses. Importantly, the remarkable genetic diversity of T. cruzi lineages also contributes to clinical heterogeneity, influencing immune evasion, therapeutic responses, and vaccine feasibility. This review analyzes the impact of immunogenetics on host-parasite interactions in Chagas disease and explores its implications for personalized therapy approaches. Recent research, particularly over the last decade, has indicated that processes including antigenic variation, extracellular vesicle-mediated regulation, and disruption of host signaling pathways facilitate parasite persistence. Host genetic variables significantly influence susceptibility, disease development, and treatment outcomes, including changes in Human Leukocyte Antigen (HLA) genes, cytokine gene polymorphisms, and immunogenetic determinants of cardiac pathology. These findings underscore the potential of immunogenetic markers as tools for prognosis and as targets for personalized therapies. However, there are still considerable research deficiencies. Inadequate comprehension of gene-environment interactions, lack of representation of varied populations, and inconsistencies in study design limit the use of immunogenetic findings in therapeutic settings. At present, the concept of personalized medicine in Chagas disease remains largely aspirational, better understood as a framework for precision public health or stratified interventions guided by host immunogenetic and parasite lineage data. Addressing these issues necessitates comprehensive genomic research, mechanistic investigations of host-parasite interactions, and clinical validation of genetic markers. This study emphasizes the necessity of incorporating immunogenetics into personalized patient management strategies based on existing evidence. This integration has the potential to improve diagnosis, enhance treatment efficacy, and inform preventive interventions, thereby advancing personalized therapy for Chagas disease.
- Extrapulmonary manifestations of SARS-CoV-2 infection and COVID-19 vaccine adverse effectsPublication . Botelho, Monica Catarina; Poma, Anello Marcello; Wu, JianNo abstract available
- Application of a Pilot Screening Program for Familial Hypercholesterolemia in a High-Complexity Hospital CenterPublication . Radojkovic, Claudia; Honorato, Paula; Portiño, René; Martínez, Catalina; Saez, Katia; Bourbon, Mafalda; Muñoz, Isabel; Alvarado, Cristóbal; Guzmán, Enrique; Bustos, Paulina; Alonso, Rodrigo; Sánchez, AndreaOne of the current challenges is the early identification of patients with Familial Hypercholesterolemia (FH) through clinical diagnosis and genetic analysis to initiate treatment and prevent the development of atherosclerotic disease. Aim: To describe the results of a pilot program for opportunistic screening of Familial Hypercholesterolemia index cases in a highly complex hospital laboratory. Materials and methods: Retrospective cross-sectional convenience recruitment study. Search for patients with clinical suspicion of FH was conducted by analyzing the lipid profile of users from the Las Higueras Hospital of Talcahuano, between 2019 and 2021. Patients were selected and stratified according to LDL-C concentrations using the Dutch Lipid Clinic Network (DLCN) Criteria. Patients with a DLCN score >6 were selected as candidates for genetic diagnosis. Results: 36,804 lipid profiles were obtained, of which 19,021 corresponded to a unique lipid profile per patient. After applying the exclusion criteria, 98 patients suspected of FH. According to the DLCN criteria, 5 patients were stratified with a definitive clinical diagnosis (DLCN ≥8) and 4 with a probable diagnosis of FH (DLCN 6-7). In 4 of the 6 patients who were contacted, 3 genetic variants associated with FH were identified. Conclusion: This work corresponds to the first report on the application of an FH screening program in a highly complex hospital center in Chile and allowed the definitive diagnosis of pediatric and adult patients with FH. These results demonstrate the importance of implementing an opportunistic screening program and performing genetic analysis for FH variants to a definitive diagnosis.