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ABSTRACT Background Methods Results Conclusions This study investigates the gender‐specific genetic influence of the single nucleotide polymorphism (SNP) rs1111875 on diabetes risk within the Taiwanese population using data from the Taiwan Biobank. Diabetes mellitus, particularly type 2 diabetes (T2D), is influenced by genetic factors, and the rs1111875 SNP near the hematopoietically expressed homeobox (HHEX) gene has been linked to T2D susceptibility.The study included 69,272 participants after excluding those from arsenic‐polluted areas and those with incomplete data. Logistic regression models were used for analyses.The analyses revealed that the CT genotype of rs1111875 was associated with an increased risk of diabetes (OR = 1.092, 95% CI = 1.030–1.157, P = 0.003), as was the TT genotype (OR = 1.280, 95% CI = 1.165–1.407, P < 0.001). The effect was more pronounced in women (CT: OR = 1.118, 95% CI = 1.036–1.207, P = 0.004; TT: OR = 1.404, 95% CI = 1.243–1.585, P < 0.001). Men exhibited a higher overall risk of diabetes (OR = 1.565, 95% CI = 1.445–1.694, P < 0.001) and had a higher prevalence (12.71% vs 7.80%, P < 0.001) compared to women.The findings underscore the importance of considering gender differences in genetic studies of diabetes and suggest that personalized diabetes management strategies should account for both genetic and gender‐specific risk factors. This research contributes to the broader understanding of genetic determinants of diabetes and their interaction with gender, aiming to enhance personalized healthcare strategies for diabetes prevention and treatment. [ABSTRACT FROM AUTHOR]

The spinal muscular atrophy (SMA) phenotype strongly correlates with the SMN2 gene copy number. However, the severity and progression of the disease vary widely even among affected individuals with identical copy numbers. This study aimed to investigate the impact of genetic variability in oxidative stress, inflammatory, and neurodevelopmental pathways on SMA susceptibility and clinical progression. Genotyping for 31 genetic variants across 20 genes was conducted in 54 SMA patients and 163 healthy controls. Our results revealed associations between specific polymorphisms and SMA susceptibility, disease type, age at symptom onset, and motor and respiratory function. Notably, the TNF rs1800629 and BDNF rs6265 polymorphisms demonstrated a protective effect against SMA susceptibility, whereas the IL6 rs1800795 was associated with an increased risk. The polymorphisms CARD8 rs2043211 and BDNF rs6265 were associated with SMA type, while SOD2 rs4880, CAT rs1001179, and MIR146A rs2910164 were associated with age at onset of symptoms after adjustment for clinical parameters. In addition, GPX1 rs1050450 and HMOX1 rs2071747 were associated with motor function scores and lung function scores, while MIR146A rs2910164, NOTCH rs367398 SNPs, and GSTM1 deletion were associated with motor and upper limb function scores, and BDNF rs6265 was associated with lung function scores after adjustment. These findings emphasize the potential of genetic variability in oxidative stress, inflammatory processes, and neurodevelopmental pathways to elucidate the complex course of SMA. Further exploration of these pathways offers a promising avenue for developing personalized therapeutic strategies for SMA patients. [ABSTRACT FROM AUTHOR]

Pepper (Capsicum spp.) is one of the most important crops worldwide. Understanding the species' genetic background is key to preserve agrodiversity on-farm, to contribute to a more diverse and resilient agrifood sector, and to find new sources of variation that could be useful in future breeding programs. In this regard, varietal groups bred in insular environments have gained special interest as they have evolved quite isolated from continental forms, with a limited genetic exchange. The present work explores the diversity of a plethora of Balearic landraces, corresponding to different local varietal types, through phenotyping and genotyping-by-sequencing (GBS). Mallorca and Eivissa landraces were phenotyped according to a comprehensive list of descriptors for plant, leaf, flower, fruit, pollen, and seed and were genotyped with single nucleotide polymorphism (SNP) markers; population structure and their patterns of diversity were studied. The results showed a considerable morphological diversity for most traits analyzed, within and between landraces. On the whole, in regard to genetic patterns, relatively low levels of heterozygosity and moderate genetic diversity for the studied landraces were found although some of them exhibited diverse patterns. The materials were not grouped in specific clusters associated with each island, but mainly according to varietal types. These findings can serve as the basis for studying divergent evolutionary patterns associated with the corresponding populations. Finally, the results can contribute to further elucidation of the genetic basis of Balearic landraces and serve as an inspiring case of study for other insular endemisms of cultivated species. [ABSTRACT FROM AUTHOR]

Strict biennials are among the least known lifecycles in plant ecology due to their rarity in nature, and their population genetics still remain unknown. The present study addressed the strict biennial lifecycle and associated population genetics of Pedicularis hallaisanensis , an endangered endemic plant in Korea. All P. hallaisanensis individuals were counted in August from 2021 to 2023 in the wild population of Gayasan National Park, and lifecycle and morphological changes were monitored monthly. A de novo draft genome and single nucleotide polymorphism (SNP) analysis were used to study the population's genetic structure. P. hallaisanensis strictly requires a 2-year lifecycle per generation, including 8 and 10 months of growing periods as a first-year seedling and second-year adult, respectively. Facultative annual and perennial lifecycles were undetected, resulting in odd-year and even-year flowering cohorts. Permutational multivariate analysis of variance on the detected 3,716 SNPs demonstrated that the flowering group (p < 0.005), microhabitat (p < 0.001), and their interaction (p < 0.01) had a significant effect on genetic structure, which was differentiated between odd-year and even-year flowering cohorts. Other cluster analyses also showed that a microhabitat under historical anthropogenic interventions contained lowered genetic diversity due to a decreased genetic distance between odd-year and even-year flowering cohorts (p < 0.05). Overall, the findings suggest that excessive anthropogenic interventions should be avoided to preserve genetic diversity in the wild P. hallaisanensis population. Moreover, conservation programs for similar biennial plants should collect wild breeds from both odd-year and even-year flowering cohorts to improve the genetic diversity of artificially propagated individuals. [ABSTRACT FROM AUTHOR]

Introduction: Individuals who develop new‐onset diabetes have been identified as a high‐risk cohort for pancreatic cancer (PC), exhibiting an incidence rate nearly 8 times higher than the general population. Hence, the targeted screening of this specific cohort presents a promising opportunity for early pancreatic cancer detection. We aimed to develop and validate a novel model capable of identifying high‐risk individuals among those with new‐onset diabetes. Methods: Employing the UK Biobank cohort, we focused on those developing new‐onset diabetes during follow‐up. Genetic and clinical characteristics available at registration were considered as candidate predictors. We conducted univariate regression analysis to identify potential indicators and used a 5‐fold cross‐validation method to select optimal predictors for model development. Five machine learning algorithms were used for model development. Results: Among 12,735 patients with new‐onset diabetes, 100 (0.8%) were diagnosed with PC within 2 years. The final model (area under the curve, 0.897; 95% confidence interval, 0.865–0.929) included 5 clinical predictors and 24 single nucleotide polymorphisms. Two threshold cut‐offs were established: 1.28% and 5.26%. The recommended 1.28% cut‐off, based on model performance, reduces definitive testing to 13% of the total population while capturing 76% of PC cases. The high‐risk threshold is 5.26%. Utilizing this threshold, only 2% of the population needs definitive testing, capturing nearly half of PC cases. Conclusions: We, for the first time, combined clinical and genetic data to develop and validate a model to determine the risk of pancreatic cancer in patients with new‐onset diabetes using machine learning algorithms. By reducing the number of unnecessary tests while ensuring that a substantial proportion of high‐risk patients are identified, this tool has the potential to improve patient outcomes and optimize healthcare sources. [ABSTRACT FROM AUTHOR]

Numerous studies have established associations between single nucleotide polymorphisms (SNPs) and various behavioral and neurodevelopmental conditions. This study explores the links between SNPs in candidate genes involved in central nervous system (CNS) physiology and their implications for the behavioral and emotional aspects in children and teenagers. A total of 590 participants, aged 7–15 years, from the Early Life Exposures In Mexico To Environmental Toxicants (ELEMENT) cohort study in Mexico City, underwent genotyping for at least one of 15 CNS gene‐related SNPs at different timepoints. We employed multiple linear regression models to assess the potential impact of genetic variations on behavioral and cognitive traits, as measured by the Behavioral Assessment System for Children (BASC) and Conners parent rating scales. Significant associations were observed, including the rs1800497 TC genotype (ANKK1) with the Cognitive Problems/Inattention variable (p value = 0.003), the rs1800955 CT genotype (DDR4) with the Emotional Lability Global index variable (p value = 0.01), and the rs10492138 GA and rs7970177 TC genotypes (GRIN2B) with the Depression variable (p values 0.007 and 0.012, respectively). These finds suggest potential genetic profiles associated with "risk" and "protective" behaviors for these SNPs. Our results provide valuable insights into the role of genetic variations in neurobehavior and highlight the need for further research in the early identification and intervention in individuals at risk for these conditions. [ABSTRACT FROM AUTHOR]

Vincristine-induced peripheral neuropathy (VIPN) is an adverse effect of regimens used for the treatment of aggressive B-cell non-Hodgkin lymphoma (B-NHL). A single-nucleotide polymorphism (SNP) in the promotor region of the CEP72 gene has been identified as risk factor for the development of VIPN in children. To validate these results in adults we aimed to determine the association of the high-risk CEP72 (rs924607 TT genotype) with the occurrence and severity of VIPN. Analysis of SNP rs924607 (TT, CC or CT) was performed in all enrolled patients with available blood samples with a TaqMan genotyping assay. Rates and grades of VIPN were assessed prospectively as part of the RICOVER-60 trial. CEP72 genotype could be assessed in 519 patients. VIPN data was available for 499/519 patients who were included in the final analysis. 286 (57%) patients developed VIPN of any grade during treatment. Grade 2–4 VIPN occurred in 33% (166/499) of patients. The high-risk CEP72 TT genotype at rs924607 was identified in 97/499 (19%) patients. The TT genotype was not correlated with VIPN in the overall study population compared to patients with either CC or CT genotypes (p = 0.748). However, in the subgroup of female patients, the TT genotype was associated with increased occurrence of any-grade VIPN as well as grade 2–4 VIPN as compared to patients with either CC or CT genotypes (p = 0.016 and p = 0.020, respectively). Thus, the SNP rs924607 in the CEP72 gene is associated with increased VIPN incidence in female patients with aggressive B-NHL treated with CHOP chemotherapy. Trial registration ClinicalTrials.gov identifier: NCT00052936, submission date: 2005-06-23, EudraCT Number: 2010-019587-36. [ABSTRACT FROM AUTHOR]

Background: Temporomandibular joint disorder (TMD), a prevalent orofacial disorder with complex aetiologies and considerable socioeconomic costs. This underscores the critical importance of developing a comprehensive understanding of the risk factors associated with TMD, as existing research is hindered by deficiencies in establishing causal relationships and the limitations of traditional research methodologies. Objectives: This research explores the causal link between certain risk factors and temporomandibular joint disorder (TMD) through Mendelian randomization (MR), providing multidimensional perspectives in addressing this worldwide health issue. Methods: Utilizing instrumental variables, we applied advanced statistical methods, including the weighted median, inverse variance weighted (IVW) and MR‐Egger, to evaluate the impact of twelve potential risk factors on TMD. Results: Our results identified a significant positive association of TMD with malocclusion (p <.001), sleeping disorders (p =.006), anxiety (p =.002), major depression (p =.0002), daily cigarettes consumption (p =.029) and autoimmune diseases (p =.039). Conversely, a negative association was observed with educational attainment (p =.003). Conclusion: These findings suggest that malocclusion, sleeping disorders, anxiety, major depression, daily cigarettes consumption and autoimmune diseases, could potentially increase TMD risk while educational attainment might mitigate its increase. No direct causal relationships were established between serum 25‐hydroxyvitamin D levels, menopause, frequent alcohol consumption, coffee intake and severely worn dentition and TMD. [ABSTRACT FROM AUTHOR]

Purpose We aimed to explore the causal relationship between human serum metabolites and angina pectoris. Methods This study used two-sample Mendelian randomization (MR) analysis to assess the association between 486 serum metabolites and angina pectoris. The analytical methods employed to reduce study bias included inverse variance weighted, MR-Egger, and weighted median method. A comprehensive sensitivity analysis was performed using the leave-one-out method, while instrumental variable pleiotropy was tested with MR-Pleiotropy RESidual Sum and Outlier. Metabolic pathways of angina-associated metabolites were analysed on the MetaboAnalyst metabolomics analysis tool platform. Results In this study, 42 serum metabolites were found to be strongly associated with angina pectoris. They mainly belonged to seven groups: amino acids, carbohydrates, cofactors and vitamins, lipids, nucleotides, unknown metabolites, and exogenous substances. Pipecolate posed the highest risk for the development of angina pectoris among the 42 serum metabolites. The main metabolic pathways associated with angina pectoris were glycine, serine, threonine metabolism, primary bile acid biosynthesis, and caffeine metabolism. Conclusion We identified 25 high-risk and 17 protective human serum metabolites associated with angina pectoris. Their associated major metabolic pathways were also determined. The serum metabolite pipecolate was significantly and positively correlated with the risk of angina pectoris. This finding may serve as a valuable reference for testing serum markers associated with angina pectoris. Key message What is already known on this topic Recently, some progress has been made in screening biomarkers of angina serum metabolism. However, no studies explored the link between serum metabolites and angina pectoris using MR analysis. What this study adds In this study, Mendelian randomization analysis was conducted for the first time on the association between human serum metabolites and angina pectoris, and 42 serum metabolites were found to be strongly associated with angina pectoris. How this study might affect research, practice, or policy This study might assist in the clinical diagnosis and treatment of angina pectoris and advance coronary heart disease prevention and treatment. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the potential relationship between multiple sclerosis (MS) and coronavirus disease 2019 (COVID-19) outcomes using Mendelian randomization analysis. Specifically, it evaluates whether genetic factors, including the single-nucleotide polymorphism (SNP) rs10191329, influence the susceptibility of MS patients to three COVID-19 outcomes [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospitalized COVID-19, and severe COVID-19]. This study utilized genomewide association study summary statistics from the International Multiple Sclerosis Genetics Consortium to conduct a Mendelian randomization analysis. SNPs strongly associated with MS were selected to examine their impact on COVID-19 outcomes. The analysis focused on identifying any causal associations between MS and COVID-19 severity, as well as assessing the role of interferon beta (IFNb) treatment in modifying these outcomes. The results suggest a potential association between MS and an increased risk of COVID-19, but individuals carrying the rs10191329 SNP appeared less likely to develop severe COVID-19. This SNP, located within the DYSF-ZNF638 locus, may influence immune responses and MS severity, highlighting its relevance for personalized treatment strategies. Importantly, no significant causal relationship was found between IFNb treatment and the three COVID-19 outcomes, indicating that the findings in treated patients differ from those observed in untreated patients. This suggests that IFNb may offer protective effects against SARS-CoV-2 in MS patients. These findings underscore the importance of genetic factors, such as rs10191329, in shaping the clinical outcomes of MS patients in the context of COVID-19. Further research should explore targeted therapies and personalized approaches for managing MS during the ongoing pandemic. [ABSTRACT FROM AUTHOR]

Introduction: Antimicrobial resistance (AMR) in Brucella melitensis, the causative agent of brucellosis, is of growing concern, particularly in low and middle-income countries. This study aimed to explore the genetic basis of AMR in B. melitensis strains from India. Methods: Twenty-four isolates from humans and animals were subjected to antimicrobial susceptibility testing and whole-genome sequencing. Results: Resistance to doxycycline (20.80%), ciprofloxacin (16.67%), cotrimoxazole (4.17%), and rifampicin (16.67%) was observed. Genome analysis revealed efflux-related genes like mprF, bepG, bepF, bepC, bepE, and bepD across all isolates, however, classical AMR genes were not detected. Mutations in key AMR-associated genes such as rpoB, gyrA, and folP were identified, intriguingly present in both resistant and susceptible isolates, suggesting a complex genotype–phenotype relationship in AMR among Brucella spp. Additionally, mutations in efflux genes were noted in resistant and some susceptible isolates, indicating their potential role in resistance mechanisms. However, mutations in AMR-associated genes did not consistently align with phenotypic resistance, suggesting a multifactorial basis for resistance. Discussion: The study underscores the complexity of AMR in B. melitensis and advocates for a holistic multi-omics approach to fully understand resistance mechanisms. These findings offer valuable insights into genetic markers associated with AMR, guiding future research and treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Aging is an irreversible progressive decline in physical function. Graves' disease (GD) is a common cause of hyperthyroidism and is characterized by elevated levels of the thyroid hormone (TH). High TH levels are associated with aging and a shortened lifespan. The causal relationship between GD and aging has yet to be investigated. Methods: We used genome-wide association study (GWAS) datasets and Mendelian randomization (MR) analysis to explore the causal link between GD and aging. To assess the statistical power of instrumental variables (IVs), F-statistics and R2 were used. MR analysis was conducted using inverse-variance weighting (IVW), MR-Egger, weighted median, and weighted mode. The odds ratio (OR) and 95% CI were calculated to estimate the relative risk of GD to the outcomes. The Cochran Q test, I2, MR-PRESSO test, and MR-Egger regression intercept were calculated using statistical and leave-one-out analyses to test the heterogeneity, horizontal pleiotropy, and stability of the IVs on the outcomes. Results: F-statistics of the five IVs were greater than 10, and the R2 values ranged from 0.033 to 0.156 (R2 > 0.01). According to the results of the IVW analysis, GD had no causal effect on facial aging (p = 0.189), age-related macular degeneration (p = 0.346), and Alzheimer's disease (p = 0.479). There was a causal effect of GD on the remaining outcomes: telomere length (TL) (OR = 0.982; 95%CI:0.969–0.994; p = 0.004), senile cataract (OR = 1.031; 95%CI:1.002–1.060; p = 0.033), age-related hearing impairment (OR = 1.009; 95%CI:1.004–1.014; p = 0.001), chronic obstructive pulmonary disease (COPD) (OR = 1.055; 95%CI:1.008–1.103; p = 0.020), and sarcopenia (OR = 1.027; 95%CI:1.009–1.046; p = 0.004). Conclusions: GD accelerates the occurrence of age-related phenotypes including TL, senile cataracts, age-related hearing impairment, COPD, and sarcopenia. In contrast, there are no causal linkages between GD and facial aging, age-related macular degeneration, or Alzheimer's disease. Further experimental studies could be conducted to elucidate the mechanisms by which GD facilitates aging, which could help slow down the progress of aging. [ABSTRACT FROM AUTHOR]

Background: Genetic factors, including the Hedgehog Interacting Protein (HHIP) gene, play a crucial role in Chronic Obstructive Pulmonary Disease (COPD) susceptibility. This study examines the association between HHIP gene polymorphisms and COPD susceptibility, phenotypes, and serum IL-17 and IL-18 levels in a Han Chinese population. Methods: A case-control study was conducted with 300 COPD patients and 300 healthy controls in Chinese Han population. Participants underwent genotyping for HHIP gene polymorphisms, pulmonary function tests, and quantitative CT scans. DNA samples were sequenced using a custom chip targeting the HHIP gene. Serum IL-17 and IL-18 levels were measured by enzyme-linked immunosorbent assay. Associations between SNPs, COPD susceptibility, and phenotypes were analyzed using logistic and multiple linear regression models, adjusting for confounders. Results: Our study identified the rs11100865 polymorphism in the HHIP gene as significantly associated with COPD susceptibility (OR 2.479, 95% CI 1.527–4.024, P = 2.39E-04) after screening 114 SNPs through rigorous quality control. Stratified analyses further indicated this association was particularly in individuals aged 60 or older. Serum levels of IL-17 and IL-18 were significantly elevated in COPD patients compared to controls, with rs11100865 showing a notable association with IL-18 levels (B = 49.654, SE = 19.627, P = 0.012). However, no significant associations were observed between rs11100865 and serum IL-17 levels, COPD-related imaging parameters, or clinical phenotypes. Conclusion: This study identified a significant association between HHIP gene polymorphisms and COPD susceptibility in a Han Chinese population, with connections to inflammation, but found no significant associations between this SNP and COPD-related imaging or clinical phenotypes. Trial registration: www.chictr.org.cn ID: ChiCTR2300071579 2023-05-18. [ABSTRACT FROM AUTHOR]

We reported a performance during an implementation of prenatal cell-free (cf) DNA screening using single nucleotide polymorphism (SNP) approach in our accredited laboratory.Prospective audit with prompt intervention was set for the processing of 2,502 samples from singleton pregnancy from August 2017 to July 2019. Risks of trisomy 21 (T21), T18, T13, monosomy X (XO), and other sex chromosome aneuploidies (SCAs) were clarified by a proprietary bioinformatics algorithm.Laboratory failure occurred in 192 samples (7.7 %) as a result of inadequate sequencing (n=144), fundamental limitation of the testing (n=19), and obvious human error (n=29). Faulty setting of the calibration curve was the most common human error (n=22/29). After a redraw (n=110), 79 (71.8 %) were settled. Overall, 2,389/2,502 samples (95.5 %) were reportable. Thirty-five samples were high-risk for T21 (n=19), T18 (n=5), T13 (n=1), XO (n=3), and other SCAs (n=7), respectively. Positive predictive values calculated from either prenatal confirmatory tests or postnatal findings were 93.8 % (n=16), 100 % (n=4), 50 % (n=2), and 83.3 % (n=6) for T21, T18, XO, and other SCAs, respectively, with high sensitivity and specificity (>99.9 %). Vanishing twin was detected from 1 out of 4 samples with detected additional haplotypes.An overall performance of SNP-based prenatal cf-DNA screening during our initial implementation can be optimized with proactive approach. The technical know-how was a significant limiting factor for adopting the technology. The lessons learnt may be of interest to the academic laboratory considering adopting their own test instead of sending blood to a testing service of a supplier. [ABSTRACT FROM AUTHOR]

Objective: To analyze the genotypes of VZV in Jiangsu province to identify vaccine strains and wild strains, providing a molecular biological background for the effective prevention and control of varicella. Method: Stratified sampling was used to collect herpes fluid or throat swab from patients diagnosed with varicella. ORF22 was carried out, and the restriction enzyme site of ORF38, ORF54 and ORF62 were detected. Results: All 207 virus strains were Clade 2 type by sequencing the PCR products of ORF22. The sequencing results showed that five SNP sites changed compared to the Dumas reference strain(Clade 1). From A to G at 37,902, from T to c at 38,055, from A to C at 38,081, and from G to A at 38,177, from G to A at 39,394. The prevalent VZV genotypes in Jiangsu is consistent with the P-Oka. The restriction enzyme site analysis of PCR amplification products from ORF38 (PstI), ORF54 (BglI), ORF62 (SmaI) showed that all 207 virus strains were wild-type. There were two different types of the wild strains, and 183 strains (88.4%) were PstI (+), BglI (+), SmaI (-). The wild strains between different regions showed no significant differences (χ2 = 0.05, P = 0.982). Conclusions: The prevalent VZV genotypes are Clade 2 and the prevalent virus strains are wild strains in Jiangsu Province, the primary wild strain observed is mainly PstI (+), BglI (+), SmaI (-). [ABSTRACT FROM AUTHOR]

Background and objective: Genetic polymorphism studies in families and twins indicated the heritability of depression. However, the association between genes with genetic polymorphism and depression provides various findings and remains unclear. Therefore, we conducted a systematic review and meta-analysis to determine the genes with their polymorphism associated with the symptomatic depression known as major depressive disorder (MDD). Materials and methods: PubMed and Scopus were searched for relevant studies published before May 22, 2023 (1968–2023), and 62 were selected for this review. The study's bias risk was investigated using the Newcastle–Ottawa scale. Gene functional enrichment analysis was investigated for molecular function (MF) and biological process (BP) and pathways. A meta-analysis of the studied genes that were replicative in the same single nucleotide polymorphism was conducted using a random-effect model. Results: The 49 genes involved in MDD were studied and engaged in several pathways, such as tryptophan metabolism or dopaminergic and serotonergic synapses. Based on gene overlapping in MF and BP, 13 genes with polymorphisms were identified as related to MDD. Most of them were only studied once. Solute carrier family 6 member 4 (SLC6A4) overlapping between MF and BP and brain-derived neurotrophic factor (BDNF) as unique to BP were replicative studied and used in the meta-analysis. The polymorphism of SLC6A4 SS and LS genotypes increased the occurrence of MDD development but not significantly [odd ratio (OR) = 1.39; 95% confidence interval (CI) = 0.87–2.22; P = 0.16 and OR = 1.13; 95% CI = 0.84–1.53; P = 0.42, respectively]. A similar result was observed for BDNF rs6265 GG (OR = 1.26; 95% CI = 0.78–2.06; P = 0.35) and BDNF rs6265 AA genotypes (OR = 1.12; 95% CI = 0.77–1.64; P = 0.56). These studies indicated low bias and significant heterogeneity. Conclusion: At least 13 studied genes with polymorphisms were involved in MDD development according to MF and BP, but not significantly. These results suggest that MDD development risk factors might require genetic and other factors for interaction and induction. [ABSTRACT FROM AUTHOR]

The association between the MCM6-13910-C/T polymorphism and lactose intolerance in individuals of European descent is well known. However, the notion that having a single versus a double allelic mutation might influence one's phenotype has been hypothesized. This study investigated whether patients with the three genotypes C/C, C/T, T/T differed in response to a lactose tolerance test (LTT) in a Danish setting. Anonymized data on 603 individuals with results for both genetic test and LTT were investigated. Mean delta glucose values were plotted for the time points of the LTT (0, 15, 30, 45 and 60 min) for the C/C, C/T and T/T genotype, respectively. Further, the agreement between the three genotypes and the diagnostic interpretation of the LTT were examined using a cut-off of > 1.4 mmol/L rise in glucose. In subjects with the C/C genotype, mean glucose delta levels were markedly lower compared to both the C/T and T/T genotypes at all time points. Overall, a difference between mean glucose delta values among the C/T and T/T genotype could not be shown. Using a LTT cut-off of > 1.4 mmol/L, the proportions of lactose intolerant LTT results for each genotype were as follows: 58% among C/C, 5% among C/T, and 7% among T/T. In a Danish healthcare setting, the C/C genotype was on average associated with a smaller glucose response during a LTT when compared to the C/T and T/T genotypes. A marked difference in the LTT response among the C/T and T/T genotype was not observed. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To investigate the genetic determinants affecting the rate of change in CSF total tau (t-tau). METHODS: This study conducted a genome-wide association study (GWAS) on longitudinal CSF t-tau and genotype data from 319 non-Hispanic Caucasians within the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. The aim was to identify genetic determinants influencing the rate of change in CSF t-tau, a key biomarker in AD. RESULTS: The GWAS identified a significant single nucleotide polymorphism (SNP), rs17149074, within the C9orf171 (CFAP77) gene region that showed significant association with changes in CSF t-tau over time. Additionally, five other SNPs--rs10916844, rs10916846, rs9425869, rs3744474, and rs8078303--were found to potentially influence CSF t-tau variability. CONCLUSIONS: These findings not only enhance our understanding of t-tau's progression in AD but also suggest that these identified SNPs could serve as novel genetic biomarkers, potentially providing novel insights in the prognostic landscape of AD by refining the predictive value of CSF-tau measurements [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a major public health problem worldwide, currently ranking third in cancer incidence and second in mortality. Multiple genes and environmental factors have been involved in the complex and multifactorial process of CRC carcinogenesis. VDR is an intracellular hormone receptor expressed in both normal epithelial and cancer colon cells at various levels. Several VDR gene polymorphisms, including FokI and BsmI, have been evaluated for their possible association with CRC susceptibility. The aim of our study was to investigate these two SNPs for the first time in Romanian CRC patients. FokI (rs228570 C>T) and BsmI (rs1544410 A>G) were genotyped by real-time polymerase chain reaction (RT-PCR) in 384-well plates using specific TaqMan predesigned probes on a ViiA™ 7 RT-PCR System. A total of 441 subjects (166 CRC patients and 275 healthy controls) were included. No statistically significant difference was observed between CRC patients and controls when we compared the wild-type genotype with heterozygous and mutant genotypes for both FokI (OR 0.85, 95% CI: 0.56–1.28; OR 0.95, 95% CI: 0.51–1.79, respectively) and BsmI (OR 0.97, 95% CI: 0.63–1.49; OR 1.10, 95% CI: 0.65–1.87, respectively) or in the dominant and recessive models. Also, we compared allele frequencies, and no correlation was found. Moreover, the association between these SNPs and the tumor site, TNM stage, and histological type was examined separately, and there was no statistically significant difference. In conclusion, our study did not show any association between FokI and BsmI SNPs and CRC susceptibility in a Romanian population. Further studies including a larger number of samples are needed to improve our knowledge regarding the influence of VDR polymorphism on CRC susceptibility. [ABSTRACT FROM AUTHOR]

Sustainable fisheries management is important for the continued harvest of the world's marine resources, especially as they are increasingly challenged by a range of climatic and anthropogenic factors. One of the pillars of sustainable fisheries management is the accurate identification of the biological units, i.e., populations. Here, we developed and implemented a genetic baseline for Atlantic herring harvested in the Norwegian offshore fisheries to investigate the validity of the current management boundaries. This was achieved by genotyping > 15,000 herring from the northern European seas, including samples of all the known populations in the region, with a panel of population‐informative SNPs mined from existing genomic resources. The final genetic baseline consisted of ~1000 herring from 12 genetically distinct populations. We thereafter used the baseline to investigate mixed catches from the North and Norwegian Seas, revealing that each management area consisted of multiple populations, as previously suspected. However, substantial numbers (up to 50% or more within a sample) of herring were found outside of their expected management areas, e.g., North Sea autumn‐spawning herring north of 62° N (average = 19.2%), Norwegian spring‐spawning herring south of 62° N (average = 13.5%), and western Baltic spring‐spawning herring outside their assumed distribution area in the North Sea (average = 20.0%). Based upon these extensive observations, we conclude that the assessment and management areas currently in place for herring in this region need adjustments to reflect the populations present. Furthermore, we suggest that for migratory species, such as herring, a paradigm shift from using static geographic stock boundaries towards spatial dynamic boundaries is needed to meet the requirements of future sustainable management regimes. [ABSTRACT FROM AUTHOR]

Objective: Cell‐free DNA (cfDNA) is used as a biomarker after transplantation to detect graft injury, relying on the donor fraction (DF). We have established a PCR‐based approach allowing us to separately quantify absolute values of dd‐cfDNA and recipient‐derived cfDNA (rd‐cfDNA). We aimed to present typical clinical scenarios after heart transplantation (HTx) to illustrate the advantages of absolute cfDNA values over DF. Methods: We used the cfDNA results of our cohort (509 samples of 52 patients followed during the first year after HTx) as background and determined the trajectories of cfDNA in specific clinical situations. We profiled an uncomplicated clinical course, viral and bacterial infections, acute and chronic rejection, and false‐negative and false‐positive rejections in six patients (five adults, one child). Results: There was a substantial discrepancy between relative (DF) and absolute cfDNA‐levels in several clinical situations. Rd‐ and dd‐cfDNA were independently elevated during episodes of rejection and infection and were better suited to depict treatment response than DF alone. Conclusions: Absolute quantification of cfDNA may offer clinically relevant information additive to DF in various situations after HTx and could be helpful for more accurate monitoring of diagnosis and treatment of rejection. [ABSTRACT FROM AUTHOR]

Background: Recipient's VEGF‐A polymorphisms have been reported to be associated with the risk of acute allograft rejection. However, an association of the donor's VEGF‐A gene polymorphism with rejection remained unelucidated till now. Methods: In this study, VEGF‐A gene SNPs at nine loci were analyzed in 160 kidney donors and recipients with rejection (rejectors, n = 80) and without rejection (non‐rejectors, n = 80). Blood VEGF‐A mRNA, plasma VEGF level, and intragraft VEGF expression were also analyzed by RT‐PCR, ELISA, and immunohistochemistry, respectively. Results: On comparing between the donor and rejectors, the polymorphic genotypes of VEGF –634 C>G [GG genotype, p < 0.0001; OR (95% CI) = 17.74 (5.16–60.96)]; VEGF –1154 G>A [AG genotype, p < 0.0001, OR (95% CI) = 16.07 (3.68–70.15)]; VEGF +936 C>T [CT genotype, p < 0.0001, OR (95% CI) = 178.64 (23.28–1370.9), and TT genotype, p < 0.0001; OR (95% CI) = 3149 (278.91–35 553)]; VEGF –1455 T>C [CC genotype, p value = 0.0464, OR (95% CI) = 3.13 (1.07–9.10)]; VEGF –2578 C>A [CA genotype, p = 0.0426, OR (95% CI) = 4.62 (1.03–20.59), and AA genotype, p value < 0.0001, OR (95% CI) = 21.89 (4.94–97.04)]; VEGF –2549 18 bp Insertion/Deletion [ID genotype, p value < 0.0001, OR (95% CI) = 27.27 (3.61–205.73) and DD genotype, p value < 0.0001, OR (95% CI) = 25.18 (3.30–191.89) were significantly associated with acute rejection risk. On comparing rejectors versus non‐rejectors, GA genotype of VEGF –1190 G>A and TC genotype of VEGF –1455 T>C were associated with the risk of rejection. On comparing donor VEGF between rejectors and non‐rejectors, CG genotype of VEGF –634 C>G, AG of VEGF –1154 G>A; GA of VEGF –1190 G>A were associated with rejection. The blood VEGF‐A mRNA and plasma VEGF levels were higher in the rejectors group compared to non‐rejectors. Conclusions: Besides the recipient's VEGF SNPS, the donor's VEGF SNPs are also associated with the risk of acute rejection and may be closely monitored in evaluation to determine the risk of rejection. [ABSTRACT FROM AUTHOR]

Objectives Mechanisms of non-typhoidal Salmonella (NTS) resistance to azithromycin have rarely been reported. Here we investigate the epidemiology and genetic features of 10 azithromycin-resistant NTS isolates. Methods A total of 457 NTS isolates were collected from a tertiary hospital in Guangzhou. We performed antimicrobial susceptibility tests, conjugation experiments, efflux pump expression tests, whole-genome sequencing and bioinformatics analysis to conduct the study. Results The results showed that 10 NTS isolates (2.8%) were resistant to azithromycin with minimum inhibitory concentration values ranging from 128 to 512 mg/L and exhibited multidrug resistance. The phylogenetic tree revealed that 5 S. London isolates (AR1–AR5) recognized at different times and departments were closely related [3–74 single-nucleotide polymorphisms (SNPs)] and 2 S. Typhimurium isolates (AR7 and AR8) were clones (<3 SNPs) at 3-month intervals. The azithromycin resistance was conferred by mph (A) gene found on different plasmids, including IncFIB, IncHI2, InFII, IncC and IncI plasmids. Among them, IncFIB, InFII and IncHI2 plasmids carried different IS 26 -class 1 integron (intI1) arrangement patterns that mediated multidrug resistance transmission. Conjugative IncC plasmid encoded resistance to ciprofloxacin, ceftriaxone and azithromycin. Furthermore, phylogenetic analysis demonstrated that mph (A)-positive plasmids closely related to 10 plasmids in this study were mainly discovered from NTS, Escherichia coli , Klebsiella pneumonia and Enterobacter hormaechei. The genetic environment of mph (A) in 10 NTS isolates was IS 26 - mph (A)- mrx (A)- mphR (A)-IS 6100 /IS 26 that co-arranged with intI1 harbour multidrug-resistant (MDR) gene cassettes on diverse plasmids. Conclusions These findings highlighted that the dissemination of these plasmids carrying mph (A) and various intI1 MDR gene cassettes would seriously restrict the availability of essential antimicrobial agents for treating NTS infections. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaw (MRONJ) is a rare side effect of antiresorptive drugs that significantly hinders the quality of life of affected patients. The disease develops in the presence of a combination of factors. Important pathogenetic factors include inflammation, inhibition of bone remodeling, or genetic predisposition. Since the first description of this rare side effect in 2003, a growing body of data has suggested a possible role for genetic factors in the disease. Several genes have been suggested to play an important role in the pathogenesis of MRONJ such as SIRT1, VEGFA, and CYP2C8. With the development of molecular biology, newer methods such as miRNA and gene expression studies have been introduced in MRONJ, in addition to methods that can examine the base sequence of the DNA. Describing the complex genetic background of MRONJ can help further understand its pathophysiology as well as identify new therapeutic targets to better manage this adverse drug reaction. [ABSTRACT FROM AUTHOR]

Background: Irisin was found to correlate with coronary artery disease (CAD) in diabetic patients. This study investigated the association of irisin and FNDC5 (SNP rs3480) with the presence and severity of CAD in T2DM. Methods: This cross-sectional study included 100 patients with T2DM divided into two groups, DM group (n = 50), including patients without CAD and CAD group (n = 50), including those confirmed to have CAD by coronary angiography. Irisin was measured. SNP rs3480 genotyping of FNDC5 was done. Results: Irisin levels were significantly lower in the CAD group (p < 0.001). The CAD group had significantly higher HbA1c and lower HDL (p < 0.001). Patients with controlled DM had significantly higher irisin levels (p < 0.001). single nucleotide polymorphism (SNP) rs3480 was not associated with irisin levels, and the FNDC5 rs3480 AA reference allele was significantly associated with significant CAD. Conclusion: Irisin appears to be protective against developing CAD in diabetic patients. Irisin level was an independent predictor of significant CAD in diabetic patients combined with the FNDC5 rs3480 genotype. Clinical trial registration number: NCT04957823 [ABSTRACT FROM AUTHOR]

The TMPRSS2 protease plays a key role in the entry of the SARS-CoV-2 into cells. The TMPRSS2 gene is highly polymorphic in humans, and some polymorphisms may affect the susceptibility to COVID-19 or disease severity. rs75603675 (c.23G > T) is a missense variant that causes the replacement of glycine with valine at position 8 (p.G8V) in the TMPRSS2 isoform 1. According to GnomAD v4.0.0 database, the allele frequency of the rs75603675 on a global scale is 38.10 %, and range from 0.92 % in East Asian to 40.77 % in non-Finnish European (NFE) population. We analyzed the occurrence of the rs75603675 in two cohorts of patients, the first with severe/critical COVID-19 enrolled in a French hospital (42 patients), and the second with predominantly asymptomatic/pauci-symptomatic/mild COVID-19 enrolled in an Italian hospital (69 patients). We found that the TMPRSS2 -c.23T minor allele frequency was similar in the two cohorts, 46.43 % and 46.38 %, respectively, and higher than the frequency in the NFE population (40.77 %). Chi-square test provided significant results (p < 0.05) when the genotype data (TMPRSS2 -c.23T/c.23T homozygotes + TMPRSS2 -c.23G/c.23T heterozygotes vs. TMPRSS2 -c.23G/c.23G homozygotes) of the two patient groups were pooled and compared to the expected data for the NFE population, suggesting a possible pathogenetic mechanism of the p.G8V substitution. We explored the possible effects of the p.G8V substitution and found that the N-terminal region of the TMPRSS2 isoform 1 contains a signal for clathrin/AP-2-dependent endocytosis. In silico analysis predicted that the p.G8V substitution may increase the accessibility to the endocytic signal, which could help SARS-CoV-2 enter cells. • Polymorphism rs75603675 is a missense variant that causes the replacement of glycine with valine at position 8 in TMPRSS2 • Minor allele of rs75603675 is associated with increased susceptibility to COVID-19 in a retrospective cohort analysis. • G8V substitution affects the stability of the N-terminal region of the TMPRSS2 as revealed by molecular dynamic simulation. • In silico analysis shows that an endocytic signal may be more exposed in TMPRSS2-p.8V variant, helping the virus enter cells. [ABSTRACT FROM AUTHOR]

Increased cardiovascular risk has been associated with certain platelet morphological parameters, and several single nucleotide polymorphisms (SNPs) have been reported to be linked. Still, little is known about their role among children with type 1 diabetes mellitus (T1DM). So, we aimed to investigate platelet parameters and lipid profile changes in relation to rs7961894 SNP in children with T1DM. Eighty children with T1DM and eighty apparently healthy controls participated in this cross-sectional study. Platelet count, mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), HbA1c, triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol were measured, and atherogenic indices were calculated. Using a real-time polymerase chain allelic discrimination technique, rs7961894 SNP was genotyped. Children with T1DM had significantly higher MPV, PDW, TC, and LDL-C compared to controls. 25% of patients had rs7961894 CT genotype with significantly higher MPV, PDW, PCT, LDL-C, triglycerides, Castelli's risk index II (CRI II), and atherogenic index of plasma (AIP) compared to CC genotyped patients. MPV correlated significantly with CRI II and AIP, PDW with CRI II, while PCT correlated substantially with HbA1c, LDL-C, CRI II, and AIP. rs7961894 CT genotype was a significant dependent predictor of the changes in MPV, PDW, and PCT in multivariate regression analysis. Conclusion: In children with T1DM, rs7961894 CT genotype is significantly linked to MPV, PDW, and PCT changes, which showed a substantial relationship to CRI II and AIP, highlighting the importance of monitoring these patients to identify potential cardiovascular risks early. What is Known: • Platelets and dyslipidemia are involved in atherosclerosis pathogenesis • Changes in platelet activity and morphological parameters in diabetes mellitus are contradictory • rs7961894 single nucleotide polymorphism is associated with significant changes in mean platelet volume (MPV) with no available data in children What is New: • Children with type 1 diabetes mellitus exhibited significantly higher values of MPV and platelet distribution width (PDW) • rs7961894 CT genotype was a dependent predictor of the changes in MPV, PDW, and plateletcrit (PCT) values • Diabetic children with the rs7961894 CT genotype showed substantial alterations in lipid parameters with a strong correlation between MPV, PDW, and PCT and Castelli's risk index II and the atherogenic index of plasma [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the utility of 24 single nucleotide polymorphism (SNP) loci associated with iris color and hair color in phenotypic identification of the Han Chinese population in Fujian Province. The selected SNPs, known for their strong correlation with specific human phenotypic features, provide valuable reference data for developing a molecular phenotypic identification system. Methods: A multiplex genotyping assay system was established with primers for the 24 SNPs linked to iris color and hair color synthesized based on existing literature. In total, 235 unrelated individuals of Han Chinese ethnicity in Fujian Province were included in this study. PowerStats v12 was employed to calculate forensic parameters associated with the 24 SNP loci, including gene frequencies, genotype frequencies, minor allele frequencies, discrimination power (DP), polymorphism information content (PIC), and observed heterozygosity (Ho). Hardy- Weinberg equilibrium tests were conducted for each locus. The SNP genotyping results were uploaded to the HIrisPlex model (https://HIrisPlex.erasmusmc.nl/) to predict iris and hair colors, and the inferred results were compared with manually assessed images. The accuracy of pigment phenotype inference was evaluated by using ROC curves in SPSS 26.0 software. Results: The accuracy rates of inferring brown iris and black hair phenotypes were 99.6% and 99.5%. The area under the curve (AUC) values were 0.923 and 0.980, respectively. Conclusions: The 24 SNP loci demonstrated high accuracy in inferring iris color and hair color; it seems to be a useful tool for forensic phenotypic identification and anthropological or evolutionary applications. Establishment of suitable pigment classification criteria and optimized prediction models is based on revealing more phenotypic genetic markers. [ABSTRACT FROM AUTHOR]

Small ruminant lentivirus (SRLV) infections are spread in the flocks of sheep and goats all over the world, causing economic loss. Although only a fraction of infected animals develop disease symptoms, all of them may shed the virus, causing uncontrolled spread of the infection. Antibodies against the virus can be detected in the blood of infected animals and are the main marker of infection. Additionally, in most infected animals, proviral DNA can also be detected, but at different levels. Due to the lack of treatment or vaccines, the most effective strategy to prevent SRLV infections are control programmes introduced by several countries based on the elimination of seropositive individuals from the flock. An alternative approach, which has currently become the rationale, is an identification of host factors which may predispose certain individuals or breeds to resistance or susceptibility to small ruminant lentivirus infection. In our work, attention was paid to goats of the Carpathian breed infected with SRLV. Available RNA-seq results from the blood of 12 goats with a determined level of SRLV proviral load were used to analyse single nucleotide polymorphisms (SNPs) by the variant calling method. Six SNPs within five genes (POU2AF1, BCAT2, TMEM154, PARP14, UBASH3A) were selected for genotyping to determine their association with the level of small ruminant lentivirus proviral DNA in a group of 60 goats. Interestingly, in seronegative individuals, only the TT genotype of the PARP14 gene was observed, while the TMEM154 CC genotype was found only in seropositive goats. Both genes may be considered potential markers for resistance/susceptibility to SRLV infection. In contrast, polymorphisms identified in POU2AF1 and UBASH3A genes seemed to be deleterious for respective protein functions; therefore, these genes are less likely to be recognised as resistance/susceptibility markers of SRLV infection. [ABSTRACT FROM AUTHOR]

Context Thiazide-induced hyponatremia is one of the most common forms of hyponatremia, but its pathogenesis is incompletely understood. Recent clinical data suggest links with prostaglandin E2 (PGE2) and a single nucleotide polymorphism (SNP) in the prostaglandin transporter gene (SLCO2A1), but it is unknown if these findings also apply to the general population. Objective To study the associations between serum sodium, thiazide diuretics, urinary excretions of PGE2, and its metabolite (PGEM), and the rs34550074 SNP in SLCO2A1 in the general population. Design Prospective population-based cohort study (Rotterdam Study). Setting General population. Participants 2178 participants (65% female, age 64 ± 8 years) Intervention(s) None. Main Outcome Measure(s) Serum sodium levels. Results Higher urinary PGE2 excretion was associated with lower serum sodium: difference in serum sodium for each 2-fold higher PGE2 −0.19 mmol/L [95% confidence interval (CI) −0.31 to −0.06], PGEM −0.29 mmol/L (95% CI −0.41 to −0.17). This association was stronger in thiazide users (per 2-fold higher PGE2 −0.73 vs −0.12 mmol/L and PGEM −0.6 vs −0.25 mmol/L, P for interaction <.05 for both). A propensity score matching analysis of thiazide vs non-thiazide users yielded similar results. The SNP rs34550074 was not associated with lower serum sodium or higher urinary PGE2 or PGEM excretion in thiazide or non-thiazide users. Conclusion Serum sodium is lower in people with higher urinary PGE2 and PGEM excretion, and this association is stronger in thiazide users. This suggests that PGE2-mediated water reabsorption regulates serum sodium, which is relevant for the pathogenesis of hyponatremia in general and thiazide-induced hyponatremia specifically. [ABSTRACT FROM AUTHOR]

Coke oven emissions (COEs) contain a variety of polycyclic aromatic hydrocarbons (PAHs), which can cause damage to the human cardiovascular system. In addition, myocardial mitochondria are susceptible to damage in hypertensive patients. However, it is not clear whether genetic variation, in single nucleotide polymorphisms (SNPs) in PINK1 affects COEs exposure-induced abnormal blood pressure. We surveyed and tested 518 workers exposed to COEs and statistically analyzed them with SPSS 21.0 software. SBP was greater in the high-exposure group than in the low-exposure group. Generalized linear model analysis showed that the interaction of PINK1 rs3738136 (GA+AA) and COEs had an effect on SBP [β(95%CI) = -6.537(−12.072, −1.002), p = 0.021] and DBP [β(95%CI) = -4.811(−8.567, −1.056), p = 0.012]. This study is the first to identify the role of PINK1 rs3738136 in COE- induced abnormal blood pressure, and to prove that the abnormal blood pressure of workers is the result of environmental and genetic factors. [ABSTRACT FROM AUTHOR]

Exploring genetic resources through genomic analyses has emerged as a powerful strategy to develop common bean (Phaseolus vulgaris L.) cultivars that are both productive and well-adapted to various environments. This study aimed to identify genomic regions linked to morpho-agronomic traits in Mesoamerican and Andean common bean accessions and to elucidate the proteins potentially involved in these traits. We evaluated 109 common bean accessions over three agricultural years, focusing on traits including the grain yield (YDSD), 100-seed weight (SW), number of seeds per pod (SDPD), number of pods per plant (PDPL), first pod insertion height (FPIH), plant height (PLHT), days to flowering (DF), and days to maturity (DPM). Using multilocus methods such as mrMLM, FASTmrMLM, FASTmrEMMA, ISIS EM-BLASSO, and pLARmEB, we identified 36 significant SNPs across all chromosomes (Pv01 to Pv11). Validating these SNPs and candidate genes in segregating populations is crucial for developing more productive common bean cultivars through marker-assisted selection. [ABSTRACT FROM AUTHOR]

To investigate the association between single nucleotide polymorphism (SNP) at the rs3918188, rs1799983 and rs1007311 loci of the endothelial nitric oxide synthase (eNOS) gene and genetic susceptibility to systemic lupus erythematosus (SLE) in northeastern China. The base distribution of eNOS gene rs3918188, rs1799983 and rs1007311 in 1712 human peripheral blood samples from Northeast China was detected by SNaPshot sequencing technology. The correlation between genotype, allele and gene model of these loci of the eNOS gene and the genetic susceptibility to SLE was investigated by logistic regression analysis. The results of the differences in the frequency distribution of their gene models were visualised using R 4.3.2 software. Finally, HaploView 4.2 software was used to analyse the relationship between the haplotypes of the three loci mentioned above and the genetic susceptibility to SLE. A multifactor dimensionality reduction (MDR) analysis was used to determine the best SNP-SNP interaction model. The CC genotype and C allele at the rs3918188 locus may be a risk factor for SLE (CC vs AA: OR = 1.827, P < 0.05; C vs A: OR = 1.558, P < 0.001), and this locus increased the risk of SLE in the dominant model and the recessive model (AC + CC vs AA: OR = 1.542, P < 0.05; CC vs AA + AC: OR = 1.707, P < 0.001), while the risk of SLE was reduced in the overdominant model (AC vs AA + CC: OR = 0.628, P < 0.001). The GT genotype and T allele at locus rs1799983 may be a protective factor for SLE (GT vs GG: OR = 0.328, P < 0.001; T vs G: OR = 0.438, P < 0.001) and this locus reduced the risk of SLE in the overdominant model (GT vs GG + TT: OR = 0.385, P < 0.001). There is a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene. Among them, the formed haplotype AG increased the risk of SLE compared to GG. AT and GT decreased the risk of SLE compared to GG. In this study, the eNOS gene rs3918188 and rs1799983 loci were found to be associated with susceptibility to SLE. This helps to deeply explore the mechanism of eNOS gene and genetic susceptibility to SLE. It provides a certain research basis for the subsequent exploration of the molecular mechanism of these loci and SLE, as well as the early diagnosis, treatment and prognosis of SLE. [ABSTRACT FROM AUTHOR]

To explore whether rs2073244 at PAX9 increased susceptibility for full-term low birth weight infants and whether indoors passive smoking exposure has a combined effect with rs2073244 on newborn low birth weight (LBW), a 1:2 paired case–control study of LBW newborns was conducted at Xiamen University Affiliated Women and Children’s Hospital from March 2010 to October 2013. The rate of indoor passive smoking exposure in the LBW group was higher than it in the NBW group (p = 0.019). GG of PAX9 rs2073244 decreased the risk of LBW [OR = 0.38, 95% CI: (0.15-0.98)] and smaller HC [OR = 0.44, 95% CI:(0.20-0.98)]. The relative excess risk for LBW contributed by the additive interaction between the rs2073244 risk genotypes AG/AA and mother pregnancy passive smoking exposure was 10.679 (95%CI 1.728–65.975). Our study suggested that the AG/AA genotype of PAX9 rs2073244 might be a risk factor for LBW of full-term newborns, especially in maternal passive smoking. [ABSTRACT FROM AUTHOR]

Genetic and epigenetic alterations occur in many physiological and pathological processes. The existing knowledge regarding the association of PIWI‐interacting RNAs (piRNAs) and their genetic variants on risk and progression of prostate cancer (PCa) is limited. In this study, three genome‐wide association study datasets are combined, including 85,707 PCa cases and 166,247 controls, to uncover genetic variants in piRNAs. Functional investigations involved manipulating piRNA expression in cellular and mouse models to study its oncogenetic role in PCa. A specific genetic variant, rs17201241 is identified, associated with increased expression of PROPER (piRNA overexpressed in prostate cancer) in tumors and are located within the gene, conferring an increased risk and malignant progression of PCa. Mechanistically, PROPER coupled with YTHDF2 to recognize N6‐methyladenosine (m6A) and facilitated RNA‐binding protein interactions between EIF2S3 at 5′‐untranslated region (UTR) and YTHDF2/YBX3 at 3′‐UTR to promote DUSP1 circularization. This m6A‐dependent mRNA‐looping pattern enhanced DUSP1 degradation and inhibited DUSP1 translation, ultimately reducing DUSP1 expression and promoting PCa metastasis via the p38 mitogen‐activated protein kinase (MAPK) signaling pathway. Inhibition of PROPER expression using antagoPROPER effectively suppressed xenograft growth, suggesting its potential as a therapeutic target. Thus, targeting piRNA PROPER‐mediated genetic and epigenetic fine control is a promising strategy for the concurrent prevention and treatment of PCa. [ABSTRACT FROM AUTHOR]

Background: The foodborne bacterium Listeria monocytogenes (Lm) causes a range of diseases, from mild gastroenteritis to invasive infections that have high fatality rate in vulnerable individuals. Understanding the population genomic structure of invasive Lm is critical to informing public health interventions and infection control policies that will be most effective especially in local and regional communities. Methods: We sequenced the whole draft genomes of 936 Lm isolates from human clinical samples obtained in a two-decade active surveillance program across 58 counties in New York State, USA. Samples came mostly from blood and cerebrospinal fluid. We characterized the phylogenetic relationships, population structure, antimicrobial resistance genes, virulence genes, and mobile genetic elements. Results: The population is genetically heterogenous, consisting of lineages I–IV, 89 clonal complexes, 200 sequence types, and six known serogroups. In addition to intrinsic antimicrobial resistance genes (fosX, lin, norB, and sul), other resistance genes tetM, tetS, ermG, msrD, and mefA were sparsely distributed in the population. Within each lineage, we identified clusters of isolates with ≤ 20 single nucleotide polymorphisms in the core genome alignment. These clusters may represent isolates that share a most recent common ancestor, e.g., they are derived from the same contamination source or demonstrate evidence of transmission or outbreak. We identified 38 epidemiologically linked clusters of isolates, confirming eight previously reported disease outbreaks and the discovery of cryptic outbreaks and undetected chains of transmission, even in the rarely reported Lm lineage III (ST3171). The presence of animal-associated lineages III and IV may suggest a possible spillover of animal-restricted strains to humans. Many transmissible clones persisted over several years and traversed distant sites across the state. Conclusions: Our findings revealed the bacterial determinants of invasive listeriosis, driven mainly by the diversity of locally circulating lineages, intrinsic and mobile antimicrobial resistance and virulence genes, and persistence across geographical and temporal scales. Our findings will inform public health efforts to reduce the burden of invasive listeriosis, including the design of food safety measures, source traceback, and outbreak detection. [ABSTRACT FROM AUTHOR]

Parentage testing is crucial for forensic DNA analysis, using short tandem repeats (STRs). Single nucleotide polymorphisms (SNPs) with high minor allele frequency (MAF) are promising for human identification. This study aimed to develop SNP markers for parentage testing in the Taiwanese population and compare their accuracy with STRs. The TPMv1 SNP microarray (714,457 SNPs) was used to screen 180,000 Taiwanese individuals and analyze the SNP data using PLINK. After quality control, allelic distribution, and MAF considerations, a set of SNPs with significant inheritance information was selected. Parentage testing was conducted on 355 single parent-child pairs using both STRs and SNPs, employing three kinship algorithms: identity by descent, kinship-based inference for genome-wide association studies, and the combined paternity index/probability of paternity (CPI/PP). An Affymetrix signature probe for kinship testing (ASP) was also used. Based on the quality control and selection criteria, 176 SNPs with MAF > 0.4995 were selected from the Taiwanese population. The CPI/PP results calculated using SNPs were consistent with the STR results. The accuracy of the SNPs used in the single-parent-child parentage testing was > 99.99%. The set of 176 SNPs had a higher identification rate in the single parent-child parentage test than in the ASP. The CPI/PP value calculated using 176 SNPs was also more accurate than that calculated using ASP. Our findings suggest that these 176 SNPs could be used for single-parent-child parentage identification in the Taiwanese population. [ABSTRACT FROM AUTHOR]

Introduction: single nucleotide polymorphisms (SNPs) in exon 5 of the Glutathione-S-transferase Pi 1 (GSTP1) gene are directly associated with the progression and onset of leukemias. SNPs are common prognostic biomarkers for predicting and early onset of leukemia risk. The variant frequency of GSTP1 rs1695 (313 A>G) polymorphisms may affect various ethnic groups differently. In this study, the allelic frequency distribution of rs1695 (313 A>G) polymorphisms was assessed in the Saudi Arabian population and compared with other world populations. Material and Methods: Data were extracted from case-control studies in several ethnic groups using PubMed (Medline) and similar web databases. Results: The frequency of GSTP1 rs16955 (313 A>G) variant allele (G) was observed at 29.5% and different frequencies were significantly found in Egypt (p = 0.001), and India (p = 0.002). The prevalence of the frequency of GSTP1 rs16955 in the Saudi Arabian population was compared to that of other populations. The observed findings reveal a distinct pattern of GSTP1 rs1695 (313 A>G) polymorphism variant allele in the populations of Saudi Arabia, possibly due to differences in race. Conclusion: The observed findings can help assess the risk for the population harboring the risk allele of rs1695 (313 A>G) SNP and their subsequent susceptibility to leukemia. [ABSTRACT FROM AUTHOR]

The grasshopper Trimerotropis pallidipennis species complex is distributed across arid and semi-arid environments from North to South America, reaching high altitudes along the Andes Mountain range. Currently, there are four valid species of Trimerotropis in South America. However, some species were found to comprise several genetic lineages. Here, we describe the genetic structure, lineage diversification, and environmental requirements within the Trimerotropis species complex in South America based on sequences from the mitochondrial COI gene, 4048 single nucleotide polymorphisms, and ecological niche modelling. The analyses revealed the existence of at least five lineages: two with a restricted geographical distribution and three with a very wide one. The results provide evidence that glacial cycles promoted not only the presence of refuge areas but also the isolation of widely distributed lineages on the eastern and western sides of the southern Andes, potentially driving the emergence of the Trimerotropis sp. lineage, which can tolerate more temperate habitats. Our results provide evidence for the effects of Pleistocene climatic changes on the diversification history of a South American grasshopper species complex. [ABSTRACT FROM AUTHOR]

Objective To investigate whether there is a causal relationship between gut microbiota and autism in children using the Mendelian randomization (MR) analysis method. Methods Genetic data from 18 340 individuals collected by the MiBioGen consortium across 24 cohorts were utilized. Reliable instrumental variables were constructed by selecting genetic variations associated with 33 microbial taxa. Using results from a genome-wide association study (GWAS) on susceptibility genes for autism in children conducted in Europe, we comprehensively assessed the causal link between gut microbiota and autism using inverse variance weighting (IVW), MR-Egger regression, and weighted median estimation (WME). Results Among the three selected single nucleotide polymorphisms (SNPs), the abundance of Bacteroidetes was significantly associated with autism (OR=0.508, 95%CI: 0.267-0.966, P=0.039). The IVW results indicated that for every one standard deviation increase in Bacteroidetes abundance, the average risk of developing autism decreased by 49.2%. Conclusion This study suggests a negative causal effect of Bacteroidetes abundance on the risk of developing autism in children. [ABSTRACT FROM AUTHOR]

Cleft lip and/or palate (CL/P) are the most common congenital anomalies in the craniofacial region, leading to morphological and functional disruptions in the facial region. Their etiology involves genetic and environmental factors, with genetics playing a crucial role. This study aimed to investigate the association of four single nucleotide polymorphisms (SNPs)—rs987525, rs590223, rs522616, and rs4714384—with CL/P in the Polish population. We analyzed DNA samples from 209 individuals with CL/P and 418 healthy controls. The impact of SNPs on the presence of CL/P was assessed using multivariate logistic regression. Significant associations were found with rs987525. Specifically, the AC genotype was linked to an increased CL/P risk (odds ratio [OR] = 1.95, 95% confidence interval [CI]: 1.34–2.83, p < 0.001), while the CC genotype was associated with a decreased risk (OR = 0.46, 95% CI: 0.32–0.67, p < 0.001). Rs4714384 was also significant, with the CT genotype correlated with a reduced risk of CL/P (OR = 0.66, 95% CI: 0.46–0.94, p = 0.011). SNPs rs590223 and rs522616 did not show statistically significant associations. These results underscore the role of rs987525 and rs4714384 in influencing CL/P risk and suggest the utility of genetic screening in understanding CL/P etiology. [ABSTRACT FROM AUTHOR]

Objective: In the hypothalamic-pituitary-gonadotrophin axis, estrogen plays a key role in the regulation of bone maturation and growth plate closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in a North Indian population. Methods: Four SNPs of ESR1 (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in ISS patients and controls. Linkage disequilibrium (LD) and haplotyping were done by SNPStat and SHEsisPlus software. The extent of LD was determined by calculating D' and R2 values in SNP paired combinations. Results: Fifty-two ISS patients were compared with 68 controls. A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility. The frequencies of the rs6557177 CC genotype [p=0.030; odds ratio (OR)=0.13; 95% confidence interval (CI): 0.01-1.10] and rs543650 genotype TT (p=0.043; OR=0.29; 95% CI: 0.09-0.92) were increased in the ISS group compared with controls. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 showed strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799. Conclusion: Our study showed that the CC genotype at rs6557177 and TT genotype at rs543650 of ESR1 constituted a risk factor for developing ISS in North Indian children. These findings may lead to a better understanding of the SNPs associated with ISS susceptibility. [ABSTRACT FROM AUTHOR]

Aneuploidy is a genetic condition characterized by the loss or gain of one or more chromosomes. Aneuploidy affecting the sex chromosomes can lead to infertility in otherwise externally phenotypically normal cattle. Early identification of cattle with sex chromosomal aneuploidy is important to minimize the costs associated with rearing infertile cattle and futile breeding attempts. As most livestock breeding programs routinely genotype their breeding populations using single nucleotide polymorphism (SNP) arrays, this study aimed to assess the feasibility of integrating an aneuploidy screening tool into the existing pipelines that handle dense SNP genotype data. A further objective was to estimate the prevalence of sex chromosome aneuploidy in a population of 146,431 juvenile cattle using available genotype intensity data. Three genotype intensity statistics were used: the LogR Ratio (LRR), R‐value (the sum of X and Y SNP probe intensities), and B‐allele frequency (BAF) measurements. Within the female‐verified population of 124,958 individuals, the estimated prevalence rate was 0.0048% for XO, 0.0350% for XXX, and 0.0004% for XXY. The prevalence of XXY in the male‐verified population was 0.0870% (i.e., 18 out of 20,670 males). Cytogenetic testing was used to verify 2 of the XXX females who were still alive. The proposed approach can be readily integrated into existing genomic pipelines, serving as an efficient, large‐scale screening tool for aneuploidy. Its implementation could enable the early identification of infertile animals with sex‐chromosome aneuploidy. [ABSTRACT FROM AUTHOR]

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Aim - to analyze the current literature on the role of single nucleotide polymorphism (SNP) of human genes in shaping the clinical course of the new coronavirus disease (COVID-19). Results. Based on the results of the analysis and synthesis of the current literature on the role of SNP in shaping the clinical course and outcome of COVID-19, the clinical and prognostic significance of SNP of genes encoding receptors responsible for the penetration of SARS-CoV-2 into target cells has been demonstrated. The presence of the D-allele of the ACE gene (DD and ID genotypes) is associated with the highest risk of severe COVID-19, which makes it possible to offer it as an informative prognostic marker of COVID-19 severity. SNP of the TMPRSS2 co-receptor gene, known as the androgen responsive gene, at certain loci is prognostically important, as it leads to an increase in TMPRSS2 expression in men, which promotes virus fusion with the target cell membrane and has an unfavorable effect on the course of COVID-19 in men. The data accumulated in the current literature on the clinical and prognostic value of SNP host genes encoding the immune response has also been analyzed. The role of HLA SNP genes, genes encoding innate immunity factors (TLR), as well as genes encoding pro-inflammatory cytokines (IL-6, TNF-α, etc.) and acute-phase inflammatory components (CRP) in the development of severe COVID-19 and the risk of death has been demonstrated. Attention has been paid to the determined role of SNP in the ACE gene in the development of pulmonary embolism in patients with severe COVID-19. The article has analyzed publications on the SNP role of host genes in the development of clinical events that are currently interpreted as long COVID. The prognostic role of the IL-10 gene SNP and its receptor gene in the formation of long-term consequences of the new coronavirus infection has been demonstrated. Conclusions. SNP of host genes encoding receptors responsible for the entry of SARS-CoV-2 into target cells and SNP of genes encoding immune response have some prognostic value in assessing the risk of severe course and adverse effects of COVID-19. The accumulation of data on genetic risk factors for adverse outcomes of the new coronavirus disease will allow us to enhance the understanding of this infection pathogenesis, improve patient stratification and individualize therapeutic interventions. [ABSTRACT FROM AUTHOR]

Host–pathogen coevolution is defined as the reciprocal evolutionary changes in both species due to genotype × genotype (G×G) interactions at the genetic level determining the outcome and severity of infection. While co-analyses of hosts and pathogen genomes (co-genome-wide association studies) allow us to pinpoint the interacting genes, these do not reveal which host genotype(s) is/are resistant to which pathogen genotype(s). The knowledge of this so-called infection matrix is important for agriculture and medicine. Building on established theories of host–pathogen interactions, we here derive four novel indices capturing the characteristics of the infection matrix. These indices can be computed from full genome polymorphism data of randomly sampled uninfected hosts, as well as infected hosts and their pathogen strains. We use these indices in an approximate Bayesian computation method to pinpoint loci with relevant G×G interactions and to infer their underlying interaction matrix. In a combined single nucleotide polymorphism dataset of 451 European humans and their infecting hepatitis C virus (HCV) strains and 503 uninfected individuals, we reveal a new human candidate gene for resistance to HCV and new virus mutations matching human genes. For two groups of significant human–HCV (G×G) associations, we infer a gene-for-gene infection matrix, which is commonly assumed to be typical of plant–pathogen interactions. Our model-based inference framework bridges theoretical models of G×G interactions with host and pathogen genomic data. It, therefore, paves the way for understanding the evolution of key G×G interactions underpinning HCV adaptation to the European human population after a recent expansion. [ABSTRACT FROM AUTHOR]

Objective: Upper gastrointestinal bleeding (UGIB) has been identified as a potential adverse drug reaction associated with the use of low-dose aspirin (LDA). This study aimed to investigate the relationship between variants in the TBXA2R gene, which is involved in platelet aggregation, and the risk of UGIB in patients with cardiovascular diseases treated with LDA. Methods: A case-control study was conducted at a Brazilian hospital complex. Three groups were defined: (1) case group (n = 50): patients with cardiovascular disease who used LDA and were diagnosed with UGIB of non-variceal etiology, (2) LDA control group (n = 50): patients with cardiovascular disease who used LDA without developing UGIB, and (3) healthy control group (n = 189). Data were collected through face-to-face interviews, and blood samples were collected for the analysis of Helicobacter pylori infection and genotyping of 3 genetic variants [rs2238631 (C > T), rs4807491 (A > G), and rs1131882 (A > G)]. Results: The case group had a significantly higher frequency of carriers of the rs4807491.G allele compared to the control group of LDA users (P -value =.004). No significant difference was observed in the proportion of carriers of the rs2238631.T and 1131882.G variants between the studied groups. Carriers of rs2238631.T (OR: 4.515, 95% CI: 1.37-14.89) and rs4807491.G allele (OR: 3.232, 95% CI: 1.12-9.37) exhibited a higher risk of UGIB. Conclusion: These findings suggest that the presence of the rs2238631 and rs4807491 variant alleles is associates with a 3- to 4-fold increased risk of UGIB in patients with cardiovascular diseases treated with LDA. Future studies with larger sample sizes should confirm these results and to better identify individuals who may benefit from chronic LDA use. [ABSTRACT FROM AUTHOR]

Introduction: FOXO1 plays an important role in regulating immune processes that contribute to allergic inflammation; however, genetic variants influencing FOXO1 expression in AR pathogenesis remains unclear. This study aimed to investigate the functional effect of FOXO1 single nucleotide polymorphisms (SNPs) on AR development by performing genetic association and functional analysis studies. Methods: This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). We assessed the associations of FOXO1 transcript expression levels in peripheral blood mononuclear cells (PBMC) with AR phenotype, total nasal symptom score (TNSS), and SNP genotype in a sub-cohort of n = 658 individuals from the SMCSGES population. Associations of FOXO1 SNPs with AR were assessed in a cohort of n = 5,072 individuals from the SMCSGES population. In vitro promoter luciferase assay was used to evaluate the effect of AR-associated SNPs on FOXO1 promoter activity. Results: FOXO1 transcript expression in PBMC was significantly associated with the risk of AR (p < 0.05) and TNSS among AR patients (p < 0.0001). We identified a significant association between tag-SNPs rs9549246 and FOXO1 transcript expression in PBMC from the SMCSGES sub-cohort and the multiethnic eQTLGen consortium (false discovery rate-adjusted p < 0.05). The minor allele “A” of tag-SNP rs9549246 was significantly associated with a higher risk of AR (p = 0.04422, odds ratio = 1.21, 95% confidence interval = 1.01–1.45) in the SMCSGES genotyping cohort (n = 5,072). In vitro luciferase assay showed the minor allele “A” of rs35594717 (tagged by rs9549246) was significantly associated with a higher FOXO1 promoter activity (p < 0.05). Conclusion: FOXO1 transcript expression in PBMC has a strong association with the risk and symptom severity of AR. Genetic variants tagged by rs9549246 were shown to affect the expression of FOXO1 and contribute to the development of AR in the SMCSGES population. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus, one of the most prevalent metabolic disorders worldwide, is closely linked with an enhanced risk of atherosclerosis. However, the molecular mechanism of this linkage is not still clear. Genetic variations in the mTOR gene may increase the susceptibility of individuals to these diseases. Methods: One hundred nine diabetic patients and 375 healthy subjects participated in this study. mTOR Single Nucleotide Polymorphism (SNP) rs2295080 was determined using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Results: Comparison of genotypic, allelic, and genotypic combination frequencies between cases and controls revealed no significant result. Nevertheless, the frequency of rs2295080 GT + TT genotype was significantly more in diabetic women with atherosclerosis compared with those without atherosclerosis (p = 0.047). Besides, the rs2295080 G allele was more frequently detected in diabetic women without atherosclerosis compared to those with atherosclerosis (p = 0.046). Conclusion: The rs2295080 GT + TT genotype predisposes Iranian diabetic women to atherosclerosis, while the rs2295080 G allele protects them against atherosclerosis. However, additional experiments using larger sample sizes are needed to verify this result. [ABSTRACT FROM AUTHOR]

Background: Hypodontia is the most prevalent dental anomaly in humans, and is primarily attributed to genetic factors. Although genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNP) associated with hypodontia, genetic risk assessment remains challenging due to population-specific SNP variants. Therefore, we aimed to conducted a genetic analysis and developed a machine-learning-based predictive model to examine the association between previously reported SNPs and hypodontia in the Saudi Arabian population. Our case–control study included 106 participants (aged 8–50 years; 64 females and 42 males), comprising 54 hypodontia cases and 52 controls. We utilized TaqManTM Real-Time Polymerase Chain Reaction and allelic genotyping to analyze three selected SNPs (AXIN2: rs2240308, PAX9: rs61754301, and MSX1: rs12532) in unstimulated whole saliva samples. The chi-square test, multinomial logistic regression, and machine-learning techniques were used to assess genetic risk by using odds ratios (ORs) for multiple target variables. Results: Multivariate logistic regression indicated a significant association between homozygous AXIN2 rs2240308 and the hypodontia phenotype (ORs [95% confidence interval] 2.893 [1.28–6.53]). Machine-learning algorithms revealed that the AXIN2 homozygous (A/A) genotype is a genetic risk factor for hypodontia of teeth #12, #22, and #35, whereas the AXIN2 homozygous (G/G) genotype increases the risk for hypodontia of teeth #22, #35, and #45. The PAX9 homozygous (C/C) genotype is associated with an increased risk for hypodontia of teeth #22 and #35. Conclusions: Our study confirms a link between AXIN2 and hypodontia in Saudi orthodontic patients and suggests that combining machine-learning models with SNP analysis of saliva samples can effectively identify individuals with non-syndromic hypodontia. [ABSTRACT FROM AUTHOR]