Genetic Association Analysis Research Articles

Genetic association analysis of variants in CUZD1 with chronic pancreatitis

Genetic association analysis of variants in CUZD1 with chronic pancreatitis

Analysis of Genetic variability and Character association in Fennel (Foeniculum vulgare Mill.) Germplasm

Two hundred sixteen germplasms with six check varieties of fennel (Foeniculum vulgare Mill.) were evaluated in augmented randomized complete block design in four blocks during Rabi 2016-17 at Research Farm, SKN college of agriculture, Jobner to determine nature of variability, character association. Analysis of variance revealed significant differences among the genotypes and checks for all the characters except days to 50 per cent flowering in genotypes. The highest PCV and GCV expressed as percentage was observed for seed yield per plant followed by seeds per umbel, umbels per plant, branches per plant, umbellets per umbel, test weight, plant height, days to maturity and days to 50 per cent flowering. The high estimates of heritability and genetic advance were found for seed yield per plant, seeds per umbel, umbels per plant and branches per plant whereas it was low for days to 50 per cent flowering and days to maturity. Correlation studies revealed that seed yield per plant was significantly and positively correlated with test weight, seeds per umbel, umbellets per umbel and umbels per umbel. Out of 216 genotypes, 14 genotypes were better than the best check variety RF-125 on the basis of seed yield per plant. Some of the promising genotypes identified on the basis of seed yield per plant were UF-4, UF-16, UF-20, UF-23, UF-55, UF-61, UF-79, UF-88, UF-145, UF-149, UF-151, UF-168, UF-172 and UF-189. These superior genotypes can be used as donors in breeding programme.

Variants in the DDX6-CXCR5 autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland.

Fine mapping and bioinformatic analysis of the DDX6-CXCR5 genetic risk association in Sjögren's Disease (SjD) and Systemic Lupus Erythematosus (SLE) identified five common SNPs with functional evidence in immune cell types: rs4938573, rs57494551, rs4938572, rs4936443, rs7117261. Functional interrogation of nuclear protein binding affinity, enhancer/promoter regulatory activity, and chromatin-chromatin interactions in immune, salivary gland epithelial, and kidney epithelial cells revealed cell type-specific allelic effects for all five SNPs that expanded regulation beyond effects on DDX6 and CXCR5 expression. Mapping the local chromatin regulatory network revealed several additional genes of interest, including lnc-PHLDB1-1. Collectively, functional characterization implicated the risk alleles of these SNPs as modulators of promoter and/or enhancer activities that regulate cell type-specific expression of DDX6, CXCR5, and lnc-PHLDB1-1, among others. Further, these findings emphasize the importance of exploring the functional significance of SNPs in the context of complex chromatin architecture in disease-relevant cell types and tissues.

Quantitative and qualitative evaluation of saffron (Crocus sativus L.) for genetic variability, character association and path analysis

Different accessions of saffron were studied to analyze genetic diversity and heritable component of variation in yield and yield related traits. Dry pistil weight, fresh pistil weight, fresh flower weight corm-1 line-1, number of flowers corm-1 line-1, and big corm index, all had high genotypic coefficient of variation, heritability and genetic advance. The traits included in the selection scheme, correlation among traits (floral and agronomic) are important as varieties must have high yield associated with exemplary quality parameters. At both phenotypic and genotypic levels, the association was found significant among the traits. Stigma length and fresh flower weight had strong direct effect with respect to dry pistil weight followed by number of flowers corm-1 line-1, fresh pistil weight and big corm index. Therefore, these parameters can be taken as criteria for selection.

Genetic Variation and Association Analysis of Elite Waxy Maize Inbred Lines in South Korea

Genetic Variation and Association Analysis of Elite Waxy Maize Inbred Lines in South Korea

Association of Blood MicroRNA Expression and Polymorphisms with Cognitive and Biomarker Changes in Older Adults

BackgroundIdentifying individuals before the onset of overt symptoms is key in the prevention of Alzheimer’s disease (AD).ObjkectivesInvestigate the use of miRNA as early blood-biomarker of cognitive decline in older adults.DesignCross-sectional.SettingTwo observational cohorts (CHARIOT-PRO, Alzheimer’s Disease Neuroimaging Initiative (ADNI)).Participants830 individuals without overt clinical symptoms from CHARIOT-PRO and 812 individuals from ADNI.MeasurementsqPCR analysis of a prioritised set of 38 miRNAs in the blood of individuals from CHARIOT-PRO, followed by a brain-specific functional enrichment analysis for the significant miRNAs. In ADNI, genetic association analysis for polymorphisms within the significant miRNAs’ genes and CSF levels of phosphorylated-tau, total-tau, amyloid-β42, soluble-TREM2 and BACE1 activity using whole genome sequencing data. Post-hoc analysis using multi-omics datasets.ResultsSix miRNAs (hsa-miR-128-3p, hsa-miR-144-5p, hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-29c-3p and hsa-miR-363-3p) were downregulated in the blood of individuals with low cognitive performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The pathway enrichment analysis indicated involvement of apoptosis and inflammation, relevant in early AD stages. Polymorphisms within genes encoding for hsa-miR-29c-3p and hsa-miR-146a-5p were associated with CSF levels of amyloid-β42, soluble-TREM2 and BACE1 activity, and 21 variants were eQTL for hippocampal MIR29C expression.Conclusionssix miRNAs may serve as potential blood biomarker of subclinical cognitive deficits in AD. Polymorphisms within these miRNAs suggest a possible interplay between the amyloid cascade and microglial activation at preclinical stages of AD.

Genetic variability, character association and path coefficient analysis in rice (Oryza sativa) genotypes of semi-arid region of India

A field experiment was conducted during rainy (kharif) seasons of 2021 and 2022 at research farm of Acharya Narendra Deva University of Agriculture and Technology, Kumarganj, Ayodhya, Uttar Pradesh to find out genetic variations, trait association and path coefficient among 116 rice (Oryza sativa L.) genotypes based on grain yield and yield attributes. Variance analysis displayed extensive trait-wise variations across genotypes, indicated variability and opportunity for genetic selection of desirable traits. All the studied characters showed minimum influence of environment on the expression of trait and genetic factors. High heritability in broad sense (h2 b) and high to moderate genetic advance in per cent of the mean were recorded for all the characters. Genetic factors showed significant influence on the expression of traits, with high heritability and moderate genetic advance. Genotypic correlation with grain yield and path analysis revealed selection based on plant height, harvest index, biological yield per plant, flag leaf area, spikelet fertility, number of spikelets per panicle and seedling vigour will be more effective for increasing grain yield.

Deep learning based phenotyping of medical images improves power for gene discovery of complex disease

Electronic health records are often incomplete, reducing the power of genetic association studies. For some diseases, such as knee osteoarthritis where the routine course of diagnosis involves an X-ray, image-based phenotyping offers an alternate and unbiased way to ascertain disease cases. We investigated this by training a deep-learning model to ascertain knee osteoarthritis cases from knee DXA scans that achieved clinician-level performance. Using our model, we identified 1931 (178%) more cases than currently diagnosed in the health record. Individuals diagnosed as cases by our model had higher rates of self-reported knee pain, for longer durations and with increased severity compared to control individuals. We trained another deep-learning model to measure the knee joint space width, a quantitative phenotype linked to knee osteoarthritis severity. In performing genetic association analysis, we found that use of a quantitative measure improved the number of genome-wide significant loci we discovered by an order of magnitude compared with our binary model of cases and controls despite the two phenotypes being highly genetically correlated. In addition we discovered associations between our quantitative measure of knee osteoarthritis and increased risk of adult fractures- a leading cause of injury-related death in older individuals-, illustrating the capability of image-based phenotyping to reveal epidemiological associations not captured in the electronic health record. For diseases with radiographic diagnosis, our results demonstrate the potential for using deep learning to phenotype at biobank scale, improving power for both genetic and epidemiological association analysis.

Inflammatory Bowel Disease and Risk of Global Cardiovascular Diseases and Type 2 Diabetes.

Inflammatory bowel disease (IBD) was associated with elevated risk of cardiometabolic diseases in observational studies. We aimed to evaluate the observational and genetic associations of Crohn's disease (CD) and ulcerative colitis (UC) with multiple cardiometabolic outcomes. Our phenotypic and genetic association analyses included more than 400 000 participants who were free of major cardiovascular disease and diabetes at recruitment (2006-2010) and were followed up until December 2019 based on the UK Biobank. For the Mendelian randomization (MR) analyses, 415 and 273 single nucleotide polymorphisms associated with CD and UC, respectively, were selected as genetic instruments. Summary-level data on individual cardiometabolic outcomes were obtained from 4 different genome-wide association studies with a total of 2 248 842 participants. In the multivariable-adjusted observational analyses, CD was associated with higher risks of heart failure (hazard ratio [HR], 1.72; 95% confidence interval, 1.22-2.42) and type 2 diabetes (HR, 2.11; 95% confidence interval, 1.67-2.67) but not with myocardial infarction or ischemic stroke. UC was related to increased risks of all the assessed cardiometabolic diseases (HRs ranged from 1.29 for myocardial infarction to 1.76 for type 2 diabetes). Conversely, neither the genetic risk score for CD nor that for UC was associated with higher risk of developing cardiometabolic diseases. In 2-sample MR analyses, genetically determined CD and UC were not associated with any of the assessed cardiometabolic diseases (all P values >.05). Despite confirming the observational associations, our study does not support a causal association between IBD and elevated risk of cardiometabolic diseases.

Influence of Genetic Variability Parameters, Character Association and Path Analysis for Grain Yield and its Attributing Traits in Kodo Millet Improvement

A set of 64 genotypes of kodo millet comprising of germplasm accessions and released varieties were evaluated for their genetic variability, heritability, genetic advance as per cent of mean, character associations and path coefficients using 11 agro-morphological traits during kharif 2022 in an Alpha Lattice Design with two replications. The analysis of variance revealed the presence of significant variations among the genotypes for all the traits evaluated. High PCV and GCV were observed for the traits viz., plant height, number of tillers, panicle length, peduncle length, thumb length, grain yield, and fodder yield. It indicated the presence of substantial variability and a low environmental influence on these traits. High heritability combined with high genetic advance as per cent of mean (GAM) was observed for plant height, peduncle length, panicle length, and fodder yield, which indicated the predominance of additive gene action and selection based on these traits would be more reliable. Grain yield exhibited significant and positive correlation with days to 50% flowering, number of tillers, panicle length, number of racemes, test weight and fodder yield. Genotypic path analysis revealed that highest direct positive effect on grain yield was exhibited by days to 50% flowering, number of tillers, panicle length, test weight and fodder yield. Hence, the above-mentioned traits exhibiting positive significant correlation and positive direct effect on grain yield could be considered as important traits to be included in the selection criteria to achieve genetic improvement of grain yield in kodo millet.

Polymorphic variants at NDUFC2, encoding a mitochondrial complex I subunit, associate with cardiac hypertrophy in human hypertension

BackgroundA dysfunction of NADH dehydrogenase, the mitochondrial Complex I (CI), associated with the development of left ventricular hypertrophy (LVH) in previous experimental studies. A deficiency of Ndufc2 (subunit of CI) impairs CI activity causing severe mitochondrial dysfunction. The T allele at NDUFC2/rs11237379 variant associates with reduced gene expression and impaired mitochondrial function. The present study tested the association of both NDUFC2/rs11237379 and NDUFC2/rs641836 variants with LVH in hypertensive patients. In vitro studies explored the impact of reduced Ndufc2 expression in isolated cardiomyocytes.MethodsTwo-hundred-forty-six subjects (147 male, 59.7%), with a mean age of 59 ± 15 years, were included for the genetic association analysis. Ndufc2 silencing was performed in both H9c2 and rat primary cardiomyocytes to explore the hypertrophy development and the underlying signaling pathway.ResultsThe TT genotype at NDUFC2/rs11237379 associated with significantly reduced gene expression. Multivariate analysis revealed that patients carrying this genotype showed significant differences for septal thickness (p = 0.07), posterior wall thickness (p = 0.008), RWT (p = 0.021), LV mass/BSA (p = 0.03), compared to subjects carrying either CC or CT genotypes. Patients carrying the A allele at NDUFC2/rs641836 showed significant differences for septal thickness (p = 0.017), posterior wall thickness (p = 0.011), LV mass (p = 0.003), LV mass/BSA (p = 0.002) and LV mass/height2.7(p = 0.010) after adjustment for covariates. In-vitro, the Ndufc2 deficiency-dependent mitochondrial dysfunction caused cardiomyocyte hypertrophy, pointing to SIRT3-AMPK-AKT-MnSOD as a major underlying signaling pathway.ConclusionsWe demonstrated for the first time a significant association of NDUFC2 variants with LVH in human hypertension and highlight a key role of Ndufc2 deficiency-dependent CI mitochondrial dysfunction on increased susceptibility to cardiac hypertrophy development.

Morphological Characterization and Genetic Variability Study on Early Maturing Pigeonpea [Cajanus cajan (L.) Millsp.] Lines

Background: Pigeonpea [Cajanus cajan (L.) Millsp. (2n=22)] is the second most important pulse crop in India after chickpea. In the present study, two-hundred early maturing (less than 140 days) pigeonpea germplasm accessions were evaluated for their genetic parameters based on morphological characters and were subsequently characterized as per the DUS descriptors for pigeonpea. Genetic variability of the population was assessed through genetic parameters and character association analysis. Methods: The plant material comprised of 193 pigeonpea genotypes along with seven checks and the experiment was conducted during kharif 2020-21 and 2021-22 in augmented design. Result: The twenty-one DUS characters were recorded at different crop growth stages. Out of those, the characters for plant height, branching pattern, time to 50% flowering, colour of base of petal, pattern of streaks on petal, pod colour, pod number of seeds, seed colour, seed colour pattern, seed shape and seed size exhibited variation across the accessions. The analysis of variance was executed for the eight different biometrical characters. The highest GCV and PCV value was obtained for the character seed yield per plant (19.91 and 21.4 respectively). Almost all the yield attributing characters except plant height showed high heritability indicating that selection for the characters for crop improvement would be highly effective. Highest genetic advance was observed for the trait pods per plant (42.34) and highest genetic advance as percent of mean was obtained for seed yield per plant (38.24). Correlation analysis among the characters for yield revealed that high positive correlation existed between seed yield per plant with pods per plant (0.580). The character for PH also showed high correlation with seed yield (0.185) which is indicative that high pods per plant and tall plant character contribute significantly towards yield enhancement.

Transmission disequilibrium analysis of whole genome data in childhood-onset systemic lupus erythematosus.

Childhood-onset systemic lupus erythematosus (cSLE) patients are unique, with hallmarks of Mendelian disorders (early-onset and severe disease) and thus are an ideal population for genetic investigation of SLE. In this study, we use the transmission disequilibrium test (TDT), a family-based genetic association analysis that employs robust methodology, to analyze whole genome sequencing data. We aim to identify novel genetic associations in an ancestrally diverse, international cSLE cohort. Forty-two cSLE patients and 84 unaffected parents from 3 countries underwent whole genome sequencing. First, we performed TDT with single nucleotide variant (SNV)-based (common variants) using PLINK 1.9, and gene-based (rare variants) analyses using Efficient and Parallelizable Association Container Toolbox (EPACTS) and rare variant TDT (rvTDT), which applies multiple gene-based burden tests adapted for TDT, including the burden of rare variants test. Applying the GWAS standard threshold (5.0 × 10-8) to common variants, our SNV-based analysis did not return any genome-wide significant SNVs. The rare variant gene-based TDT analysis identified many novel genes significantly enriched in cSLE patients, including HNRNPUL2, a DNA repair protein, and DNAH11, a ciliary movement protein, among others. Our approach identifies several novel SLE susceptibility genes in an ancestrally diverse childhood-onset lupus cohort.

Effect of bilirubin and Gilbert syndrome on health: cohort analysis of observational, genetic, and Mendelian randomisation associations

ObjectivesTo compare associations between the Gilbert syndrome genotype in European populations, measured bilirubin concentrations, genetically predicted bilirubin using this genotype, and a wide range of health outcomes in a large...

Genetic Variability, Multivariate and Association Analysis for Agronomic Traits in Different Rice Genotypes

Genetic Variability, Multivariate and Association Analysis for Agronomic Traits in Different Rice Genotypes

Assessment of genetic variability, character association and path coefficient analysis in Chrysanthemum (Dendranthema x grandiflora Tzvelev)

Assessment of genetic variability, character association and path coefficient analysis in Chrysanthemum (Dendranthema x grandiflora Tzvelev)

Genetic variability, association and path analysis for yield and fruit quality components in yellow- berried nightshade (Solanum surattense)

Genetic variability, association and path analysis for yield and fruit quality components in yellow- berried nightshade (Solanum surattense)

The ERBB2 Exonic Variant Pro1170Ala Modulates Mitogen-Activated Protein Kinase Signaling Cascades and Associates with Allergic Asthma

Introduction: Previous studies have indicated the ERBB2 genetic variants in the 17q12 locus might be associated with asthma; however, the functional effects of these variants on asthma risk remain inconclusive. This study aimed to characterize the functional roles of asthma-associated ERBB2 single nucleotide polymorphisms (SNPs) in asthma pathogenesis 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). Genotype-phenotype associations were assessed by performing a genotyping assay on n = 4,348 ethnic Chinese individuals from the SMCSGES cohort. The phosphorylation levels of receptors and signaling proteins in the MAPK signaling cascades, including ErbB2, EGFR, and ERK1/2, were compared across the genotypes of asthma-associated SNPs through in vitro and ex vivo approaches. Results: The ERBB2 tag-SNP rs1058808 was significantly associated with allergic asthma, with the allele “G” identified as protective against the disease (adjusted logistic p = 6.56 × 10⁻⁹, OR = 0.625, 95% CI: 0.544–0.718). The allele “G” of rs1058808 resulted in a Pro1170Ala mutation that results in lower phosphorylation levels of ErbB2 in HaCat cells (p < 0.001), whereas the overall ERBB2 mRNA expression and the phosphorylation levels of EGFR remained unaffected. In the SMCSGES cohort, individuals carrying the genotype “GG” of rs1058808 had lower phosphorylated ERK1/2 proteins in the MAPK signaling cascade. A lower phosphorylation level of ERK1/2 was also associated with reduced asthma risk. Conclusions: The present findings highlighted the involvement of a functional exonic variant of ERBB2 in asthma development via modulating the MAPK signaling cascade.

Clinical trait-specific genetic analysis in Behçet's disease identifies novel loci associated with ocular and neurological involvement

Behçet's disease is a complex inflammatory vasculitis with a broad spectrum of clinical manifestations. The purpose of this study was to investigate the genetics underlying specific clinical features of Behçet's disease. A total of 436 patients with Behçet's disease from Turkey were studied. Genotyping was performed using the Infinium ImmunoArray-24 BeadChip. After imputation and quality control measures, logistic regressions adjusting for sex and the first five principal components were performed for each clinical trait using a case-case genetic analysis approach. A weighted genetic risk score was calculated for each clinical feature. Genetic association analyses of previously identified susceptibility loci in Behçet's disease revealed a genetic association between ocular lesions and HLA-B/MICA (rs116799036: OR = 1.85 [95% CI = 1.35–2.52], p-value = 1.1 × 10−4). The genetic risk score was significantly higher in Behçet's disease patients with ocular lesions compared to those without ocular involvement, which is explained by the genetic variation in the HLA region. New genetic loci predisposing to specific clinical features in Behçet's disease were suggested when genome-wide variants were evaluated. The most significant associations were observed in ocular involvement with SLCO4A1 (rs6062789: OR = 0.41 [95% CI = 0.30–0.58], p-value = 1.92 × 10−7), and neurological involvement with DDX60L (rs62334264: OR = 4.12 [95% CI 2.34 to 7.24], p-value = 8.85 × 10−7). Our results emphasize the role of genetic factors in predisposing to specific clinical manifestations in Behçet's disease, and might shed additional light into disease heterogeneity, pathogenesis, and variability of Behçet's disease presentation across populations.

Genetic Diversity and Population Structure in Türkiye Bread Wheat Genotypes Revealed by Simple Sequence Repeats (SSR) Markers.

Wheat genotypes should be improved through available germplasm genetic diversity to ensure food security. This study investigated the molecular diversity and population structure of a set of Türkiye bread wheat genotypes using 120 microsatellite markers. Based on the results, 651 polymorphic alleles were evaluated to determine genetic diversity and population structure. The number of alleles ranged from 2 to 19, with an average of 5.44 alleles per locus. Polymorphic information content (PIC) ranged from 0.031 to 0.915 with a mean of 0.43. In addition, the gene diversity index ranged from 0.03 to 0.92 with an average of 0.46. The expected heterozygosity ranged from 0.00 to 0.359 with a mean of 0.124. The unbiased expected heterozygosity ranged from 0.00 to 0.319 with an average of 0.112. The mean values of the number of effective alleles (Ne), genetic diversity of Nei (H) and Shannon's information index (I) were estimated at 1.190, 1.049 and 0.168, respectively. The highest genetic diversity (GD) was estimated between genotypes G1 and G27. In the UPGMA dendrogram, the 63 genotypes were grouped into three clusters. The three main coordinates were able to explain 12.64, 6.38 and 4.90% of genetic diversity, respectively. AMOVA revealed diversity within populations at 78% and between populations at 22%. The current populations were found to be highly structured. Model-based cluster analyses classified the 63 genotypes studied into three subpopulations. The values of F-statistic (Fst) for the identified subpopulations were 0.253, 0.330 and 0.244, respectively. In addition, the expected values of heterozygosity (He) for these sub-populations were recorded as 0.45, 0.46 and 0.44, respectively. Therefore, SSR markers can be useful not only in genetic diversity and association analysis of wheat but also in its germplasm for various agronomic traits or mechanisms of tolerance to environmental stresses.