Genetic Factors Research Articles

Solitary median maxillary central incisor syndrome: cone beam computed tomography illustrated review

The solitary median maxillary central incisor syndrome (SMMCI) is a rare autosomal dominant genetic syndrome characterized by the presence of a single central incisor positioned along the midline in both primary and permanent dentition. It is often associated with the holoprosencephaly spectrum, a group of brain and facial malformations. The etiopathogenesis of SMMCI is believed to involve embryonic developmental defects occurring between the 35th and 38th day of gestation, primarily affecting midline facial structures. Several genetic factors, including mutations in the Sonic Hedgehog gene on chromosome 7 and other genetic variants, have been implicated in SMMCI development. Diagnosis is typically made through clinical examination, prenatal ultrasound, and postnatal dental evaluation. Management of SMMCI requires a multidisciplinary approach involving pediatricians, otolaryngologists, neuro-pediatricians, and genetic counselors. Dental interventions may include extraction and space maintenance, orthodontic treatment, prosthodontic options, or esthetic considerations. Further research is needed to understand better the underlying mechanisms and genetic factors associated with SMCI, which will contribute to improved diagnosis and management of this syndrome.

Research progress and future trends of early-onset gastric cancer

Early onset gastric cancer (EOGC), defined as gastric cancer occurring at a younger age. Early-onset gastric cancer tends to be poorly differentiated and highly malignant. Genetic material and environmental exposure factors may be the main causes of early occurrence of gastric cancer. Prolonging the survival and improving the quality of life of patients with early-onset gastric cancer is our main research goal in the future. This article aims to elaborate on the current research status and progress of EOGC in terms of its clinicopathological characteristics, molecular genetics, microecological environment, prediction methods, treatment plans, and prognosis, while also exploring potential avenues for future research.

Multi-omics research progress in early-onset colorectal cancer

Globally, the incidence of early-onset colorectal cancer (EOCRC) among individuals younger than 50 is escalating. Compared to late-onset colorectal cancer, EOCRC exhibits distinct clinical, pathological, and molecular features, with a higher prevalence in the left colon and rectum. However, the occurrence and development of EOCRC is a multi-factor and multi-stage evolution process, which is the result of the mutual effect of environmental, genetic and biological factors, and involves the multi-level regulation mechanism of other organisms. With the development and improvement of high-throughput sequencing technology, the application of multi-omics analysis has become an important development direction to resolve the pathogenesis of complex diseases and individualized treatment plans. This article aims to review the research progress of EOCRC at the multi-omics level, providing a theoretical foundation for earlier diagnosis and more precise treatment of this diseases.

Different genetic profiles contribute to worse overall survival in patients with leptomeningeal metastases of non-small-cell lung cancer.

To assess the genetic characteristics of central nervous system (CNS) metastases from non-small-cell lung cancer (NSCLC), we gathered the genetic profiles of brain metastases (BM) and leptomeningeal metastases (LM). Our objective was to identify genetic factors contributing to poorer overall survival (OS) in NSCLC patients with LM. This study included 25 consecutive patients with BM and 52 patients with LM from Guangdong Sanjiu Brain Hospital. All participants underwent 168-target panel sequencing. Among the 25 patients with BM, TP53 was the most frequently mutated gene (44%), followed by driver genes such as EGFR and BRAF (40% and 20%, respectively). In patients with BM, EGFR_amp and CDK4 were also frequently mutated, with rates of 20% and 16%, respectively. The genetic landscape of patients with LM differed, with the top mutated genes being EGFR, TP53, EGFR_amp, CDKN2A, CCNE1, CDK4, PMS2, and PIK3CA, with mutation rates of 77%, 69%, 31%, 29%, 13%, 13%, 13%, and 12%, respectively. In our study, patients with LM exhibited significantly worse OS compared to those with BM (p = 0.029). The mutation rates of TP53, EGFR_amp, and CDKN2A varied between patients with LM and those with BM, at 69.23% vs. 44%, 30.77% vs. 20%, and 28.85% vs. 12%, respectively. Further exploration revealed that patients with BM with TP53 mutations had a shorter OS than patients without TP53 mutations (p = 0.014). Similarly, patients with LM and TP53 mutations presented with worse OS than those without TP53 mutations (p = 0.0067). LM patients with CDKN2A deletions had worse OS than those without CDKN2A deletions (p = 0.037). Additionally, patients with EGFR_amp had a shorter OS than those without EGFR_amp (p = 0.044). Patients with LM exhibited significantly worse OS than those with BM. Gene signatures, such as TP53, EGFR_amp, and CDKN2A, may account for shorter outcomes in patients with LM.

Genetic, sociodemographic, lifestyle, and clinical risk factors of heart failure aggravation events: data from the UK Biobank

Abstract Background Heart failure (HF) is the leading cause of readmission and hospitalization. Purpose This study examined the associations and clinical utilities of genetic, sociodemographic, lifestyle, laboratory, and clinical risk factors on HF aggravation. Methods Data were from 5,345 UK Biobank middle-aged adults with established HF at enrolment. We performed Cox proportional hazard regression analyses to investigate the associations related to HF admission after enrolment utilizing 24 variables encompassing sociodemographic, clinical, lifestyle, and laboratory data. To assess the impact of genetic factors, we additionally adjusted each polygenic risk score (PRS) for the three medical histories: hypertension, atrial fibrillation (AF), and coronary heart disease (CHD), where the hazard ratios were statistically significant. Results Over a median follow-up of 11.5 [10.9-12.2] years, 247 (4.6%) HF admission events occurred. Among the 24 variables, statistically significant hazard ratios were observed for 10 variables, with hypertension (3.31, 2.19-5.02), AF (2.06, 1.53-2.75), current smoking (1.63, 1.09-2.46), and coronary heart disease (1.58, 1.17-2.13) showing the highest hazard ratios, while female gender (0.65, 0.46-0.91) exhibited the smallest hazard ratio. After adjusting for each PRS individually, HTN PRS (HR 1.06, 0.94-1.21) and AF PRS (HR 1.02, 0.90-1.16) were not statistically significant, whereas CHD PRS (HR 1.15, 1.02-1.31) showed significance in relation to HF admission. In the HF admission prediction model, the C index was 0.859 (0.838-0.880) with clinical variables, and it marginally increased to 0.864 (0.843-0.885) when all factors, including the genetic factor, were applied. Conclusions Sociodemographic, clinical, laboratory, lifestyle, and genetic factors are each associated with HF aggravation with male gender, hypertension, AF, low eGFR, cigarette smoking, and CHD PRS.

Genetic and clinical risk factors for stroke recurrence with different impact by assessment age: data from the UK Biobank

Abstract Background The predictive utility of genetic risk factors added to clinical risk factors for stroke recurrence is unclear. Furthermore, whether those predictive utility change in different age groups is uncertain. This study aimed to compare the association of genetic and clinical risk factors with recurrent stroke. Methods Data were collected from 5,378 patients with a history of stroke from the UK Biobank. Cox proportional hazards regression models were used to assess the associations of genetic, demographic, lifestyle, and comorbidity risk factors with stroke recurrence, both in overall and three age-based groups. Results Over a median follow-up of 11.5 (interquartile range [IQR] 10.6–12.3) years, 417 patients had recurrent stroke. The hazard ratio (HR) for recurrent stroke was most pronounced for diabetes mellitus (HR 2.28, 95% confidence interval [CI] 1.83-2.86). Additionally, current smoking, hypertension, age, and polygenic risk score for ischemic stroke (stroke PRS) were also significantly associated with recurrent stroke. Based on concordance index (C-index, 95% CI), the strongest predictors were diabetes mellitus (0.578, 0.556-0.599) followed by age, hypertension and stroke PRS. However, the stroke PRS (0.577, 0.527-0.627) was the strongest predictor in the younger 1/3 patient group (median age 54, IQR 50-57). In addition to demographic, lifestyle, and comorbidity risk factors, genetic risk factor improved C-index of the prediction model from 0.640 (0.592-0.688) to 0.652 (0.602-0.703) in the younger group. Conclusions Recurrent stroke is significantly associated with genetic and clinical risk factors. Genetic risk factor enhances the predictive model`s accuracy, particularly in younger patients.Prediction of stroke recurrence

Single-cell multi-cohort dissection of the schizophrenia transcriptome.

The complexity and heterogeneity of schizophrenia have hindered mechanistic elucidation and the development of more effective therapies. Here, we performed single-cell dissection of schizophrenia-associated transcriptomic changes in the human prefrontal cortex across 140 individuals in two independent cohorts. Excitatory neurons were the most affected cell group, with transcriptional changes converging on neurodevelopment and synapse-related molecular pathways. Transcriptional alterations included known genetic risk factors, suggesting convergence of rare and common genomic variants on neuronal population-specific alterations in schizophrenia. Based on the magnitude of schizophrenia-associated transcriptional change, we identified two populations of individuals with schizophrenia marked by expression of specific excitatory and inhibitory neuronal cell states. This single-cell atlas links transcriptomic changes to etiological genetic risk factors, contextualizing established knowledge within the human cortical cytoarchitecture and facilitating mechanistic understanding of schizophrenia pathophysiology and heterogeneity.

Molecular mechanisms of human papilloma virus related skin cancers: A review.

The human papillomavirus (HPV) belongs to the Papillomaviridae family of viruses which includes small, double-stranded DNA viral agents. Approximately 90% of HPV infections occur asymptomatically and resolve spontaneously. However, infection with high-risk viral strains can lead to the development of preneoplastic lesions, with an increased propensity to become cancerous. The location of these malignancies includes the oral cavity, cervix, vagina, anus, and vulva, among others. The role of HPV in carcinogenesis has already been demonstrated for the aforementioned neoplasia. However, regarding skin malignancies, the mechanisms that pinpoint the role played by HPV in their initiation and progression still elude our sight. Until now, the only fully understood mechanism of viral cutaneous oncogenesis is that of human herpes virus 8 infection in Kaposi sarcoma. In the case of HPV infection, however, most data focus on the role that beta strains exhibit in the oncogenesis of cutaneous squamous cell carcinoma (cSCC), along with ultraviolet radiation (UVR) and other environmental or genetic factors. However, recent epidemiological investigations have highlighted that HPV could also trigger the onset of other non-melanocytic, for example, basal cell carcinoma (BCC), and/or melanocytic skin cancers, for example, melanoma. Herein, we provide an overview of the role played by HPV in benign and malignant skin lesions with a particular focus on the main epidemiological, pathophysiological, and molecular aspects delineating the involvement of HPV in skin cancers.

Whole-Genome Sequencing Identified a Novel Mutation in the N-Terminal Domain of KIF5A in Chinese Patients with Familial Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by progressive damage to both upper and lower motor neurons. Genetic factors are known to play a crucial role in ALS, as genetic studies not only advance our comprehension of disease mechanisms but also help unravel the complex phenotypes exhibited by patients. To gain further insights into the genetic landscape of ALS in the Chinese population and explore genotype–phenotype correlations among individuals, we conducted whole-genome sequencing to screen genes in 34 Chinese familial ALS (FALS) probands lacking the most common ALS-associated genes. Within this cohort, we identified a rare heterozygous missense mutation in the N-terminal domain of KIF5A (c.86A>G) in one of the probands. This finding is significant as mutations in the KIF5A gene have been implicated in ALS in European cohorts since 2018, predominantly characterized by C-terminal mutations. Analysis of the clinical phenotype within this familial lineage revealed a delayed onset of symptoms, an extended survival duration, and initial manifestations in both upper limbs. These observations underscore the clinical heterogeneity observed in ALS patients harboring KIF5A mutations. In conclusion, our study contributes to the growing body of evidence linking KIF5A to ALS and enhances our understanding of the intricate genetic landscape of this disease.

Blepharoplasty Online: Critical Analysis of Content and Patient Comprehensibility.

Patients frequently turn to online information for decision-making factors about aesthetic procedures. The quality of online medical content is an essential supplement to clinical education. These resources assist patients in understanding the risks, benefits, and appropriateness of their desired procedure. This study examines the breadth and readability of online blepharoplasty information, elucidating its educational utility. A depersonalized Google search was conducted using the Startpage Search Engine, investigating key phrases, "blepharoplasty decision making factors", "eye lift decision making factors", and "eyelid lift decision making factors". The first three pages of results for each search term, totaling 90 links were screened. Data were extracted for various decision-making factors, subspecialty, gender, and readability. Twenty-six websites met inclusion for analysis. Thirteen websites were plastic surgery based, five otolaryngology (ENT), five ophthalmology/oculoplastic, one oral-maxillofacial (OMFS), and two mixed-based practices. Most blepharoplasty webpages identified were that of private practice and male surgeons. Half were subspecialties other than plastic surgery. Thirteen common decision-making factors were identified. The most common factors addressed across all texts were recovery followed by cosmetic and functional goals. The least discussed were genetic factors. Average Readability exceeded the 12th grade. There were no significant differences in readability means among subspecialties. This study examines the online blepharoplasty sphere among US-based practices providing clinical education to patients. No appreciable differences among gender, subspecialty, and readability on decision-making factors were found, highlighting a consistency among surgeons. Most websites fell short of readability standards, however, emphasizing a need for clearer information to patients. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Exploring the Link between Helicobacter pylori, Gastric Microbiota and Gastric Cancer

Gastric cancer (GC) still represents one of the leading causes of cancer-related mortality and is a major public health issue worldwide. Understanding the etiopathogenetic mechanisms behind GC development holds immense potential to revolutionize patients’ treatment and prognosis. Within the complex web of genetic predispositions and environmental factors, the connection between Helicobacter pylori (H. pylori) and gastric microbiota emerges as a focus of intense research investigation. According to the most recent hypotheses, H. pylori triggers inflammatory responses and molecular alterations in gastric mucosa, while non-Helicobacter microbiota modulates disease progression. In this review, we analyze the current state of the literature on the relationship between H. pylori and non-Helicobacter gastric microbiota in gastric carcinogenesis, highlighting the mechanisms by which microecological dysbiosis can contribute to the malignant transformation of the mucosa.

Association of prenatal and postnatal exposure to air pollution with clinically diagnosed attention deficit hyperactivity disorder: a systematic review

Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder in children, originates from a multifaceted interplay of genetic, neurological, and environmental factors. Recent studies have increasingly concentrated on environmental determinants, notably air pollution, and their impact on the risk of developing ADHD. Additionally, previous research has often conflated clinically diagnosed ADHD cases with instances of mere ADHD-like symptoms, a methodology that can introduce bias and obscure the true relationship between environmental factors and ADHD. To address this oversight, our systematic review meticulously investigates the relationship between both prenatal and postnatal exposures to particular air pollutants and strictly clinically diagnosed ADHD. Our comprehensive review encompassed 801 studies from PubMed, Cochrane Library, Web of Science, and Embase databases, out of which eight met our rigorous inclusion criteria. The Newcastle-Ottawa Scale (NOS) was utilized to gauge quality and bias. Our review found substantiated the connection between prenatal exposure to PM2.5 and NOx and a heightened risk of ADHD, while exposure to PM10 during the prenatal stage was not associated with ADHD. These findings hint at varied health impacts from different particulate matters and the prospect of gender-specific susceptibilities to such exposures. We also identified an association between postnatal exposure to PM2.5, PM10, and NO2 and an increased ADHD risk, underlining the potential neurodevelopmental harms from early exposure to these pollutants. These relationships, seemingly intricate and potentially dose-dependent, underscore the need for more detailed scrutiny. The unique value of our review is in its detailed exploration of the association between specific air pollution exposures and clinically diagnosed ADHD. Our findings offer much-needed clarity in this complex domain and emphasize the importance of future research to standardize exposure and outcome metrics, probe potential mechanisms, and reduce bias and heterogeneity.

Integrative analysis of genetics, epigenetics and RNA expression data reveal three susceptibility loci for smoking behavior in Chinese Han population.

Despite numerous studies demonstrate that genetics and epigenetics factors play important roles on smoking behavior, our understanding of their functional relevance and coordinated regulation remains largely unknown. Here we present a multiomics study on smoking behavior for Chinese smoker population with the goal of not only identifying smoking-associated functional variants but also deciphering the pathogenesis and mechanism underlying smoking behavior in this under-studied ethnic population. After whole-genome sequencing analysis of 1329 Chinese Han male samples in discovery phase and OpenArray analysis of 3744 samples in replication phase, we discovered that three novel variants located near FOXP1 (rs7635815), and between DGCR6 and PRODH (rs796774020), and in ARVCF (rs148582811) were significantly associated with smoking behavior. Subsequently cis-mQTL and cis-eQTL analysis indicated that these variants correlated significantly with the differential methylation regions (DMRs) or differential expressed genes (DEGs) located in the regions where these variants present. Finally, our in silico multiomics analysis revealed several hub genes, like DRD2, PTPRD, FOXP1, COMT, CTNNAP2, to be synergistic regulated each other in the etiology of smoking.

Klinefelter syndrome: Etiology and clinical considerations in male infertility.

Klinefelter syndrome (KS) is the most prevalent chromosomal disorder occurring in males. It is defined by an additional X chromosome, 47,XXY, resulting from errors in chromosomal segregation during parental gametogenesis. A major phenotype is impaired reproductive function, in the form of low testosterone and infertility. This review comprehensively examines the genetic and physiological factors contributing to infertility in KS, in addition to emergent assisted reproductive technologies, and the unique ethical challenges KS patients face when seeking infertility treatment. The pathology underlying KS is increased susceptibility for meiotic errors during spermatogenesis, resulting in aneuploid or even polyploid gametes. Specific genetic elements potentiating this susceptibility include polymorphisms in checkpoint genes regulating chromosomal synapsis and segregation. Physiologically, the additional sex chromosome also alters testicular endocrinology and metabolism by dysregulating interstitial and Sertoli cell function, collectively impairing normal sperm development. Additionally, epigenetic modifications like aberrant DNA methylation are being increasingly implicated in these disruptions. We also discuss assisted reproductive approaches leveraged in infertility management for KS patients. Application of assisted reproductive approaches, along with deep comprehension of the meiotic and endocrine disturbances precipitated by supernumerary X chromosomes, shows promise in enabling biological parenthood for KS individuals. This will require continued multidisciplinary collaboration between experts with background of genetics, physiology, ethics and clinical reproductive medicine.

Bidirectional communication of the gut-brain axis: new findings in Parkinson’s disease and inflammatory bowel disease

Parkinson’s disease (PD) and inflammatory bowel disease (IBD) are the two chronic inflammatory diseases that are increasingly affecting millions of people worldwide, posing a major challenge to public health. PD and IBD show similarities in epidemiology, genetics, immune response, and gut microbiota. Here, we review the pathophysiology of these two diseases, including genetic factors, immune system imbalance, changes in gut microbial composition, and the effects of microbial metabolites (especially short-chain fatty acids). We elaborate on the gut–brain axis, focusing on role of gut microbiota in the pathogenesis of PD and IBD. In addition, we discuss several therapeutic strategies, including drug therapy, fecal microbiota transplantation, and probiotic supplementation, and their potential benefits in regulating intestinal microecology and relieving disease symptoms. Our analysis will provide a new understanding and scientific basis for the development of more effective therapeutic strategies for these diseases.

Association of specific ACE2 and TMPRSS2 variants with circulatory cytokines of COVID-19 Emirati patients

IntroductionThe COVID-19 pandemic represented one of the most significant challenges to researchers and healthcare providers. Several factors determine the disease severity, whereas none alone can explain the tremendous variability. The Single nucleotide variants (SNVs) in angiotensin-converting enzyme-2 (ACE2) and transmembrane serine protease type-2 (TMPRSS2) genes affect the virus entry and are considered possible risk factors for COVID-19.MethodsWe compiled a panel of gene variants from both genes and used in-silico analysis to predict their significance. We performed biological validation to assess their capacity to alter the ACE2 interaction with the virus spike protein. Subsequently, we conducted a retrospective comparative genome analysis on those variants in the Emirati patients with different disease severity (total of 96) along with 69 healthy control subjects.ResultsOur results showed that the Emirati population lacks the variants that were previously reported as associated with disease severity, whereas a new variant in ACE2 “Chr X:g.15584534” was associated with disease severity specifically among female patients. In-silico analysis revealed that the new variant can determine the ACE2 gene transcription. Several cytokines (GM-CSF and IL-6) and chemokines (MCP-1/CCL2, IL-8/CXCL8, and IP-10/CXCL10) were markedly increased in COVID-19 patients with a significant correlation with disease severity. The newly reported genetic variant of ACE2 showed a positive correlation with CD40L, IL-1β, IL-2, IL-15, and IL-17A in COVID-19 patients.ConclusionWhereas COVID-19 represents now a past pandemic, our study underscores the importance of genetic factors specific to a population, which can influence both the susceptibility to viral infections and the level of severity; subsequently expected required preparedness in different areas of the world.

Forensic evaluation of craniometric characteristics of the Kazakhstan population

BackgroundThe human skull is the part of the skeleton most frequently used in population studies, as it was more exposed to genetic factors and less exposed to environmental factors. The skull is an important component in human forensic identification. Materials and methodsThe craniometric characteristics of 186 male and 114 female skulls found on the territory of Kazakhstan were studied. Dimensions were measured using standard anthropometric methods and instruments. The results of measurements of 25 craniometric parameters are presented. Methods of descriptive and parametric statistics were used. ResultsStatistical analysis showed significant regional dimorphism, confirming theindividuality of the Kazakhstan population. Statistically significant deviations werefound in 6 male craniometric characteristics and 4 female craniometric characteristics(p<0.05). The most dimorphous variables for regional identification in Kazakhstanmales were the higher skull base and frontal chord width , full face height , condylarand bigonial width , and low mandibular body reference values (p<0.05). For females,significant statistical discrepancies were seen in the transverse diameter and skullbase width, mastoid and occipital aperture width (p<0.05). ConclusionThe recorded variations and changes in the morphology of the humanskull of the population of Kazakhstan indicate the need to develop and updateosteometric standards used in practice for specific populations. All this will significantlyimprove the accuracy of forensic identification and more fully study the biologicalpatterns of population formation, as well as evaluate the comparative effectiveness ofindividual features in the reconstruction of the population history of various populationgroups.

Landscape of TPMT and NUDT15 Pharmacogenetic Variation in a Cohort of Canadian Pediatric Inflammatory Bowel Disease Patients.

Patients with inflammatory bowel disease (IBD) exhibit considerable interindividual variability in medication response, highlighting the need for precision medicine approaches to optimize and tailor treatment. Pharmacogenetics (PGx) offers the ability to individualize dosing by examining genetic factors underlying the metabolism of medications such as thiopurines. Pharmacogenetic testing can identify individuals who may be at risk for thiopurine dose-dependent adverse reactions including myelosuppression. We aimed to evaluate PGx variation in genes supported by clinical guidelines that inform dosing of thiopurines and characterize differences in the distribution of actionable PGx variation among diverse ancestral groups. Pharmacogenetic variation in TPMT and NUDT15 was captured by genome-wide genotyping of 1083 pediatric IBD patients from a diverse Canadian cohort. Genetic ancestry was inferred using principal component analysis. The proportion of PGx variation and associated metabolizer status phenotypes was compared across 5 genetic ancestral groups within the cohort (Admixed American, African, East Asian, European, and South Asian) and to prior global estimates from corresponding populations. Collectively, 11% of the cohort was categorized as intermediate or poor metabolizers of thiopurines, which would warrant a significant dose reduction or selection of alternate therapy. Clinically actionable variation in TPMT was more prevalent in participants of European and Admixed American/Latino ancestry (8.7% and 7.5%, respectively), whereas variation in NUDT15 was more prevalent in participants of East Asian and Admixed American/Latino ancestry (16% and 15% respectively). These findings demonstrate the considerable interpopulation variability in PGx variation underlying thiopurine metabolism, which should be factored into testing diverse patient populations.

A novel locus in CSMD1 gene is associated with increased susceptibility to severe malaria in Malian children

BackgroundPlasmodium falciparum malaria is still a leading cause of child mortality in sub-Saharan Africa. The clinical manifestations of malaria range from asymptomatic infection to severe disease. The variation in clinical presentation is partly attributed to host genetic factors with estimated narrow-sense heritability of 23%. Here, we investigate the associations between candidate gene polymorphisms and the likelihood of severe malaria (SM) in a cohort of Malian children.MethodsBased on our previous genome-wide association studies (GWAS) analysis, candidate genes were selected for in-depth analysis using several criteria including gene-level GWAS scores, functional overlap with malaria pathogenesis, and evidence of association with protection or susceptibility to other infectious or inflammatory diseases. Single Nucleotide Polymorphisms (SNPs) residing within these genes were selected mainly based on p-values from previous severe malaria susceptibility GWAS studies and minor allele frequency (MAF) in West African populations.ResultsOf 182 candidate genes reported in our previous study, 11 genes and 22 SNPs residing in these genes were selected. The selected SNPs were genotyped using KASP technology in 477 DNA samples (87 SM and 390 controls). Logistic regression analysis revealed that a common intron variant, rs13340578 in CUB and Sushi Multi Domain (CSMD1) gene, is associated with increased odds of SM in recessive mode of inheritance (MAF = 0.42, OR = 1.8, 95% CI = [1.78, 1.84], p = 0.029). The SNP is in linkage disequilibrium (LD) with multiple variants with regulatory features.ConclusionTaken together, the current study showed that an intron variant rs13340578, residing in CSMD1 gene, is associated with increased susceptibility to malaria. This finding suggests that modified regulation of complement may contribute to malaria disease severity. Further studies are needed to identify the causal variants and the underlying molecular mechanisms.

Original Research Article Genetic Diversity and Association Analysis for Agronomic and Yield Related Traits in Interspecific Progenies of Pigeonpea (Cajanus cajan)

The limited genetic diversity in existing cultivars emphasizes the need for incorporating potential exotics and wild relatives in breeding programs. This study focussed on assessing genetic variation and correlations among yield traits in F8 and F9 progenies resulting from nine interspecific crosses, involving three cultivated parental lines and three wild species. Results indicate significant genotypic variation for all traits studied. Phenotypic and genotypic coefficients of variation varied across agronomic parameters. Heritability estimates ranged from 22.61% (Primary branches plant-1) to 89.35% (Days to maturity) for different traits, emphasizing the potential for selection in breeding programs. Positive correlations were observed among various traits in both progeny generations, providing insights into the interplay of genetic factors influencing pigeon pea traits. The cluster analysis revealed that, 54 interspecific cross derived lines with three parents were grouped into four clusters, indicating the greater diversity among the lines for the selection of yield related traits for pigeonpea crop improvement.