Genes

BackgroundHFE p.C282Y (c.845G>A; rs1800562) is a common missense mutation in persons of European ancestry, but we found no comprehensive tabulation of p.C282Y allele frequencies in Iberia. MethodsWe performed computerized and manual searches to identify evaluable reports of p.C282Y alleles in population/control cohorts [≥]50 subjects in Iberia. We tabulated numbers of subjects, nominal geographic sites of cohort recruitment, cohort characteristics, corresponding latitudes and longitudes, and...

STUDY QUESTION[Do structural genomic variants, that can be identified by using optical genome mapping, contribute to male infertility?] SUMMARY ANSWER[By using optical genome mapping we can identify several types of structural variants, both known and new, that may contribute to male infertility.] WHAT IS KNOWN ALREADY[Traditional approaches such as karyotyping, CFTR and chromosome Y microdeletion testing are successful in explaining clinical findings in [~]30% of MI patients, leaving the rest...

IntroductionAdverse drug reactions (ADRs) remain a major public health issue, and genetic factors contribute importantly to interindividual variability in drug response. Pharmacogenetic testing helps reduce ADR risk by optimizing drug selection and dosage, particularly in monogenic disorders. Material and MethodsWhole-exome sequencing of 6,739 samples from the Russian population was performed using the MGIEasy Universal DNA Library Prep Set on the DNBSEQ-G400 platform (MGI). Variants in 48 gene...

BackgroundPersonalized pharmacotherapy requires systematic consideration of genetic factors influencing drug efficacy and safety. The accumulation of large-scale whole-exome sequencing (WES) data provides an opportunity to assess population frequencies of clinically significant pharmacogenetic variants; however, the diagnostic applicability of exome data for pharmacogenomics remains insufficiently studied. Materials and MethodsA retrospective analysis of 6,102 anonymized sequencing datasets obt...

ObjectiveTo evaluate the analytical and clinical performance of fetal fraction (FF) enriched genome-wide noninvasive prenatal testing (GW-NIPT) for detection of clinically relevant copy number variants (CNVs) down to 1 Mb. MethodsWe retrospectively analyzed 10,501 singleton pregnancies tested with FF enrichment-based GW-NIPT between August 2023 and July 2025. CNV analysis was performed using BinDel and WisecondorX. ResultsFF enrichment increased median FF to 24% (2.4-fold increase). Clinically...

This study examined awareness, attitudes, and perceived barriers regarding genetic counseling among individuals in Derna District, focusing on its role in preventing genetic disorders. A descriptive cross-sectional design was employed, involving 278 participants aged 17 to 45 years, selected through stratified random sampling. Data were collected using structured questionnaires and analyzed with descriptive statistics via SPSS version 26.0. The findings revealed that while 65.5% of participants ...

ObjectiveOrofacial clefts may involve the complete vertical thickness of the lip (complete) or partial thickness (incomplete). This study evaluates side preference for completeness in nonsyndromic asymmetric bilateral and unilateral cleft lip with or without cleft palate (NSCL/P). DesignWe studied 4 multiethnic cohorts from North and South America, Asia, and Africa, including 3,561 individuals with NSCL/P. Associations between cleft completeness, sex, ethnicity, and race were assessed using Chi...

BackgroundNewborn screening (NBS) has progressively expanded through technological innovations, from tandem mass spectrometry enabling expanded NBS (eNBS) to the prospect of genomic NBS (gNBS). While these developments promise earlier diagnosis and richer information, they also raise concerns regarding actionability, uncertainty, equity and psychosocial impact. As technological feasibility alone does not ensure public confidence, parental perspectives are central to evaluating future expansions....

Copy number variants (CNV) contribute significantly to the pathogenic variation associated with developmental disorders. CNV detection is often not included in standard exome sequencing (ES) analysis. Complementary methods such as chromosomal microarray are typically offered in diagnostic laboratories to diagnose pathogenic CNV. In this study, we aimed to develop an optimal approach for incorporating CNV detection within our ES analysis process for the Deciphering Developmental Disorders in Afri...

Burnout is common among genetic counselors (GCs). Clinician burnout has been found to adversely affect individual well-being, patient care, and likelihood of staying in a role. Both individual and systems solutions are needed to address clinician burnout. Mindfulness meditation (MM) is one individual-level solution that has shown promise for reducing burnout in other clinicians but has not been studied in GCs. We conducted a decentralized, parallel, three-arm randomized controlled trial comparin...

Irreversible profound hearing loss in early childhood impairs severely the development of spoken language, behavior and cognition. Hearing loss caused by aminoglycoside antibiotics in neonates treated for sepsis in intensive care units is linked to variants in the MT-RNR1 gene. Identifying the population at risk in acute medical settings is substantially limited by genotyping restricted to m.1555A>G only with 20% failure rate of the currently approved point-of-care test. We report an innovative ...

Molecular Tumour Boards (MTBs) rely on different bioinformatics tools and knowledgebases for variant annotation, oncogenicity classification, and estimation of complex biomarkers to identify actionable alterations. However, the typical bioinformatics workflow to process raw next-generation sequencing (NGS) data into clinically meaningful variants involves multiple steps and is inherently complex, thus requiring repeated manual intervention and causing delays in providing molecularly informed pre...

BackgroundThere is growing evidence that individuals with different skin phototypes require tailored approaches to achieve optimal photoprotection. Individuals with darker skin phototypes are more prone to UVA1- and visible light-induced pigmentation, whereas lighter phototypes are more susceptible to shorter wavelengths such as UVB and UVA2. Thus, skin phototype is an important determinant of sunscreen efficacy. In the present study we have asked if ethnicity - independent of phototype - is ano...

Microtia is a common congenital craniofacial malformation characterized by the partial or complete absence of the external ear structure. Despite its relatively high incidence, the pathogenesis of microtia remain poorly understood. In this study, we analyzed both single-cell and bulk RNA sequencing data from microtia cases and identified a population of COL1+HES1+ mesenchymal stem cell in perichondrium with significantly higher expression of the CRABP2 gene, a gene that encodes a nuclear transpo...

Osteoporosis and fractures are major health concerns. We developed and validated a polygenic score (PGS) for osteoporosis in a Japanese population using heel quantitative ultrasound-derived T-scores. Genome-wide association study data from 12,371 participants in the Tohoku Medical Megabank Community-Based Cohort identified genome-wide significant loci, including MBL2, TMEM135, and WNT16. PGS models were constructed and evaluated using independent datasets for model selection (n = 1,419) and vali...

Coronary artery disease (CAD) is a multifactorial condition influenced by genetic, phenotypic, and environmental factors. Traditional risk prediction models fall short in capturing the polygenic complexity of CAD, particularly in underrepresented populations. This study presents SIGMA (Scoring Importance of Genes specific to disease using Machine learning Algorithms), a novel AI-powered framework that enhances CAD risk prediction by integrating genomic and phenotypic data. Our approach leverages...

India harbors one of the most complex demographic and genetic landscapes globally, comprising more than 4600 endogamous ethnolinguistic groups shaped by multiple waves of migration, prolonged isolation and deep social stratification. Odisha, an eastern state of India, is home to 62 indigenous tribal groups, including 13 Particularly Vulnerable Tribal Groups (PVTGs), many of which remain genetically understudied. These populations provide a unique opportunity to explore fine-scale population stru...

The integration of causal effect estimates from multiple Mendelian Randomization studies has become increasingly popular. However, the presence of overlapping databases compromises traditional meta-analysis, leading to inflated variance and reduced statistical power. Here, we propose JointMR, a joint likelihood-based approach designed to integrate multiple GWAS summary databases while explicitly accounting for the covariance matrix of the Wald ratio estimates. Specifically, to accommodate potent...

BackgroundBreast cancer susceptibility gene testing (BCSG-testing) is expanding in relation to both eligibility for testing and number of genes included on testing panels. However, uncertainty remains regarding the most effective testing strategies for identifying clinically actionable germline pathogenic variants (gPVs) while balancing increased burden on breast and genetics clinical services. Patients and MethodsThe North Thames Mainstreaming of Breast Cancer Genetic Testing (NT-MBGT) program...

ObjectivesTo screen the entire genome for genes associated with risk for lateral epicondylopathy and improve understanding of underlying biological mechanisms and inform future research aimed at risk stratification and personalized prevention and treatment strategies. MethodsA genome-wide association study was conducted using UK Biobank data. Lateral epicondylopathy cases were identified based on electronic health records from individuals of European ancestry. Logistic regression tested associa...