Genes

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...

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....

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...

BackgroundThe FACE-Q Skin Cancer Module is a condition-specific patient-reported outcome measure for facial skin cancer. While its psychometric properties have been established, normative reference values that enable score interpretation in clinical practice and research are lacking. ObjectiveTo establish normative reference values for the FACE-Q Skin Cancer Module using preoperative patient data and to validate these values by comparison with a demographically matched cohort of healthy partner...

PurposeWhile genomic testing is integral to pediatric inborn errors of immunity (IEI) care, few studies have examined strategies to support its optimal delivery. This study aimed to characterize a pediatric IEI cohort and assess the impact of implementing a mainstream model-of-care (MoC). Materials/MethodsComprehensive chart audit was conducted for patients ([≤]18y) who received IEI genomic testing in Queensland, Australia, from 2017-2025. Descriptive analyses captured demographic and clinic...

Type 2 diabetes (T2D) affects 11.1% of the global population, underscoring the need for biomarkers that inform treatment response and glycemic outcomes. We evaluated the association between the FTO variant rs9939609-A and glycemic control in a Mexican population. A total of 174 individuals living with T2D from Merida and Sisal, Yucatan, were included, of whom 85% were receiving oral hypoglycemic agents as main treatment. Glycemic control was defined cross-sectionally as good ([≤]130 mg/dL, n=...

In a recent article in Science, Shenhar et al. report that human life span heritability reaches [~]55% after removing "extrinsic" mortality, roughly seven-fold higher than recent large pedigree estimates. This conclusion rests on classifying deaths from infections and accidents as environmental noise independent of genetics. This premise is biologically untenable: susceptibility to severe infection is substantially heritable, with adoptee studies showing relative risks exceeding 5 for infection ...

BackgroundExome sequencing (ES) has become a key diagnostic tool for rare diseases (RDs). However, most evidence on ES performance comes from high-income countries and patients from European ancestry. In countries such as Chile, limited access to next generation sequencing amplifies health disparities and highlights the need to identify which patients are most likely to benefit from ES. MethodsThis study presents the second phase of the Chilean DECIPHERD project, in which we performed ES in a n...

BackgroundThe Antidepressant Medications: Biology, Exposure & Response (AMBER) research programme was established to investigate the biological mechanisms underlying antidepressant action and variability in treatment response. Generation Scotland holds detailed genomic, clinical, and health information with recontacting consent, making this cohort ideal for investigating these aims. MethodsWe deployed a questionnaire, developed with input from a Lived Experience panel, to the Generation Scotlan...

The Clinical Pharmacogenetics Implementation Consortium (CPIC) bases its drug-gene recommendations on the assignment of star alleles, which map known genotypes to defined functional categories and corresponding drug dosage guidelines. The star allele framework, first proposed in 1996 for the CYP gene family and later formalized with CPICs establishment in 2010 [1, 2], remains foundational to pharmacogenomics. However, this system has notable limitations. Its dependence on a restricted set of ben...

Trade-offs form a key constraint in many aspects of organismal evolution, though they may help maintain genetic diversity. Late-onset Alzheimers disease (LOAD) shows features in common with the male-female health survival paradox: females suffer from higher prevalence and risk, as well as faster rates of cognitive decline while males suffer higher mortality. Though antagonistic pleiotropy could explain the tendency of LOAD to appear late in life, the sexually dimorphic profile suggests a role fo...

Until now, most genetic risk for vascular dementia (VD) remains unknown. Here, we firstly performed the largest cross-ancestry genome-wide association study meta-analysis comprising 5,886 VD and 1,027,883 controls of European, East Asian, South Asian, African, and Admixed American ancestry. We identified 37 genome-wide significant loci including CLU and APOE tagged by common variants and 35 loci tagged by rare variants, and demonstrated enrichment of VD heritability in lung and genetic associati...

BackgroundGenetic risk scores (GRS) for type 1 diabetes (T1D) have been developed primarily in European populations, limiting their generalisability across ancestries. Indians differ from Europeans in clinical characteristics of T1D and overall genetic architecture, yet systematic evaluation of T1D GRS performance in multi-regional Indian cohorts is lacking. MethodsThe study included 597 T1D patients and 3347 non-diabetic controls from different regions in India. Genotyping, imputation, quality...

Somatic mutations and the tumor immune microenvironment in breast tumors are important predictors of treatment response and survival, yet data for Hispanic/Latina (H/L) women are limited. Here we analyzed whole exome sequencing data from tumor/normal pairs and RNAseq data from 748 H/L women and 388 non-Hispanic White (NHW) women. Overall, the somatic profiles in tumors from H/L women were similar to NHW women. However, somatic mutations in genome organizer CTCF were significantly more common in ...

BackgroundKlebsiella pneumoniae is a common cause of neonatal sepsis in Africa, and is frequently hospital acquired. We recently reported an outbreak of multidrug-resistant K. pneumoniae sepsis amongst neonates at a rural hospital in The Gambia, West Africa, involving 57 cases and case fatality of 60%. Here we undertook a retrospective pathogen genomic epidemiology study of clinical and environmental K. pneumoniae isolated during the outbreak, to identify the outbreak strain, refine the epidemic...

BackgroundAmiodarone is a widely used antiarrhythmic which frequently induces thyroid dysfunction, including both amiodarone-induced hypothyroidism (AIH) and thyrotoxicosis (AIT). Whether genetic factors contribute to these adverse drug reactions is unknown. In this study, we aimed to identify genetic variants that influence the risk of amiodarone-induced thyroid dysfunction and to evaluate their potential to support genotype-guided risk screening. MethodsThis pharmacogenetic study comprised tw...

PurposeFuchs endothelial corneal dystrophy (FECD) is a common corneal disease and a leading indication for endothelial keratoplasty (EK). Although CTG18.1 repeat expansion is a major genetic risk factor, the contribution of polygenic background to disease progression remains unclear. We evaluated whether combining CTG18.1 expansion status with a FECD-specific polygenic risk score (PRS) enables genomic prediction of progression to EK. MethodsWe retrospectively analysed 589 individuals with FECD ...