Incidence of Arterial Hypertension in People With Periodontitis and Characterization of the Oral and Subgingival Microbiome: A Study Protocol

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. High blood pressure in particular, continues to increase throughout the global population at an increasingly fast pace. The relationship between arterial hypertension and periodontitis has been recently discussed in the context of its origins and implications. Particularly relevant is the role of the periodontal microbiome linked to persistent local and systemic inflammation, along with other risk factors and social determinants of health. The present protocol will investigate/assess the association between periodontal disease and its microbiome on the onset of hypertension, within a cohort from Mexico City. One thousand two hundred twelve participants will be studied during a 60-month period. Studies will include analysis of periodontal conditions, sampling and sequencing of the salivary and subgingival microbiome, interviews on nutritional and lifestyle habits, social determinants of health, blood pressure and anthropometric measurements. Statistical associations and several classic epidemiology and machine learning approaches will be performed to analyze the data. Implications for the generation of public policy—by early public health interventions or epidemiological surveillance approaches—and for the population empowerment—via the establishment of primary prevention recommendations, highlighting the relationship between oral and cardiovascular health—will be considered. This latter set of interventions will be supported by a carefully planned science communication and health promotion strategy. This study has been registered and approved by the Research and Ethics Committee of the School of Dentistry, Universidad Nacional Autónoma de México (CIE/0308/05/2019) and the National Institute of Genomic Medicine (CEI/2020/12). The umbrella cohort was approved by the Institutional Bioethics Committee of the National Institute of Cardiology-Ignacio Chavez (INC-ICh) under code 13-802.

Advances of Genomic Medicine in Psoriatic Arthritis

Psoriatic arthritis (PsA) is a common type of inflammatory arthritis found in up to 40% of patients with psoriasis. Although early diagnosis is important for reducing the risk of irreversible structural damage, there are no adequate screening tools for this purpose, and there are no clear markers of predisposition to the disease. Much evidence indicates that PsA disorder is complex and heterogeneous, where genetic and environmental factors converge to trigger inflammatory events and the development of the disease. Nevertheless, the etiologic events that underlie PsA are complex and not completely understood. In this review, we describe the existing data in PsA in order to highlight the need for further research in this disease to progress in the knowledge of its pathobiology and to obtain early diagnosis tools for these patients.

The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources

PURPOSE: Several groups and resources provide information that pertains to the validity of gene-disease relationships used in genomic medicine and research; however, universal standards and terminologies to define the evidence base for the role of a gene in disease, and a single harmonized resource were lacking. To tackle this issue, the Gene Curation Coalition (GenCC) was formed. METHODS: The GenCC drafted harmonized definitions for differing levels of gene-disease validity based on existing resources, and performed a modified Delphi survey with three rounds to narrow the list of terms. The GenCC also developed a unified database to display curated gene-disease validity assertions from its members. RESULTS: Based on 241 survey responses from the genetics community, a consensus term set was chosen for grading gene-disease validity and database submissions. As of December 2021, the database contains 15,241 gene-disease assertions on 4,569 unique genes from 12 submitters. When comparing submissions to the database from distinct sources, conflicts in assertions of gene-disease validity ranged from 5.3% to 13.4%. CONCLUSION: Terminology standardization, sharing of gene-disease validity classifications, and resolution of curation conflicts will facilitate collaborations across international curation efforts and in turn, improve consistency in genetic testing and variant interpretation.

Complete genomic profiles of 1,496 Taiwanese reveal curated medical insights

Background Taiwan Biobank (TWB) project has built a nationwide database to facilitate the basic and clinical collaboration within the island and internationally, which is one of the valuable public datasets of the East Asian population. This study provided comprehensive genomic medicine findings from 1,496 WGS data from TWB. Methods We reanalyzed 1,496 Illumina-based whole genome sequences (WGS) of Taiwanese participants with at least 30X depth of coverage by Sentieon DNAscope, a precisionFDA challenge winner method. All single nucleotide variants (SNV) and small insertions/deletions 1 (Indel) have been jointly called and recalibrated as one cohort dataset. Multiple practicing clinicians have reviewed clinically significant variants. Results We found that each Taiwanese has 6,870.7 globally novel variants and classified all genomic positions according to the recalibrated sequence qualities. The variant quality score helps distinguish actual genetic variants among the technical false-positive variants, making the accurate variant minor allele frequency (MAF). All variant annotation information can be browsed at TaiwanGenomes (https://genomes.tw). We detected 54 PharmGKB-reported Cytochrome P450 (CYP) genes haplotype-drug pairs with MAF over 10% in the TWB cohort and 39.8% (439/1103) Taiwanese harbored at least one PharmGKB-reported human leukocyte antigen (HLA) risk allele. We also identified 23 variants located at ACMG secondary finding V3 gene list from 25 participants, indicating 1.67% of the population is harboring at least one medical actionable variant. For carrier status of all known pathogenic variants, we estimated one in 22 couples (4.52%) would be under the risk of having offspring with at least one pathogenic variant, which is in line with Japanese (JPN) and Singaporean (SGN) populations. We also detected 6.88% and 2.02% of carrier rates for alpha thalassemia and spinal muscular atrophy (SMA) for copy number pathogenic variants, respectively. Conclusion As WGS has become affordable for everyone, a person only needs to test once for a lifetime; comprehensive WGS data reanalysis of the genomic profile will have a significant clinical impact. Our study highlights the overall picture of a complete genomic profile with medical information for a population and individuals.

A Review of Genome-Based Precision Medicine Efforts Within the Department of Defense

ABSTRACT Introduction Providing patient-specific clinical care is an expanding focus for medical professionals and researchers, more commonly referred to as personalized or precision medicine. The goal of using a patient-centric approach is to provide safer care while also increasing the probability of therapeutic success through careful consideration of the influence of certain extrinsic and intrinsic human factors in developing the patient care plan. Of increasing influence on patient care is the phenotype and genotype information gathered from employing various next-generation sequencing methods. Guided by and partnered with our civilian colleagues, clinical components within the DoD are embracing and advancing genomic medicine in many facets—from the bench to the bedside—and in many therapeutic areas, from Psychiatry to Oncology. In this PubMed-based review, we describe published clinical research and interventions within the DoD using genome-informed data and emphasize precision medicine efforts in earlier stages of development with the potential to revolutionize the approach to therapeutics. Materials and Methods The new PubMed database was searched for articles published between 2015 and 2020 with the following key search terms: precision medicine, genomic, pharmacogenetic, pharmacogenomic, US military, and Department of Defense. Results Eighty-one articles were retrieved in our initial search. After screening the abstracts for studies that only involved direct testing of (or clinical interaction with) active duty, Reserve, National Guard, or civilian personnel working within the DoD and excluding any epidemiological or microbial isolation studies, seven were included in this review. Conclusion There are several programs and studies within the DoD, which investigate or use gene-based biomarkers or gene variants to deliver more precise clinical assessment and treatment. These genome-based precision medicine efforts aim to optimize the clinical care of DoD beneficiaries, particularly service members in the operational environment.