Quantitative Trait Association Research Articles

Brugada syndrome in Japan and Europe: a genome-wide association study reveals shared genetic architecture and new risk loci.

Brugada syndrome (BrS) is an inherited arrhythmia with a higher disease prevalence and more lethal arrhythmic events in Asians than in Europeans. Genome-wide association studies (GWAS) have revealed its polygenic architecture mainly in European populations. The aim of this study was to identify novel BrS-associated loci and to compare allelic effects across ancestries. A GWAS was conducted in Japanese participants, involving 940 cases and 1634 controls, followed by a cross-ancestry meta-analysis of Japanese and European GWAS (total of 3760 cases and 11 635 controls). The novel loci were characterized by fine-mapping, gene expression, and splicing quantitative trait associations in the human heart. The Japanese-specific GWAS identified one novel locus near ZSCAN20 (P = 1.0 × 10-8), and the cross-ancestry meta-analysis identified 17 association signals, including six novel loci. The effect directions of the 17 lead variants were consistent (94.1%; P for sign test = 2.7 × 10-4), and their allelic effects were highly correlated across ancestries (Pearson's R = .91; P = 2.9 × 10-7). The genetic risk score derived from the BrS GWAS of European ancestry was significantly associated with the risk of BrS in the Japanese population [odds ratio 2.12 (95% confidence interval 1.94-2.31); P = 1.2 × 10-61], suggesting a shared genetic architecture across ancestries. Functional characterization revealed that a lead variant in CAMK2D promotes alternative splicing, resulting in an isoform switch of calmodulin kinase II-δ, favouring a pro-inflammatory/pro-death pathway. This study demonstrates novel susceptibility loci implicating potentially novel pathogenesis underlying BrS. Despite differences in clinical expressivity and epidemiology, the polygenic architecture of BrS was substantially shared across ancestries.

Statistical Analysis of Association, Heterosis, and Inheritance of Grain Yield Contributing Quantitative Traits in Segregating Lines of Wheat (Triticum aestivum L.)

Statistical Analysis of Association, Heterosis, and Inheritance of Grain Yield Contributing Quantitative Traits in Segregating Lines of Wheat (Triticum aestivum L.)

Association of quantitative traits and genetic diversity in Ethiopian sesame (Sesamum indicum L.) genotypes

To enhance sesame yield, it is important to utilize diverse parents in breeding programs and implement an effective selection procedure, which exploits the association of quantitative traits. Therefore, the objective of this experiment was to explore the correlation among quantitative traits and assess genetic variability and diversity using both qualitative and quantitative traits. Correlation coefficients indicated a noteworthy (P < 0.001) positive phenotypic (rp) and genotypic (rg) correlation between seed yield and various traits: plant height (rp = 0.60; rg = 0.58), length of the capsule-bearing zone (rp = 0.77; rg = 0.80), number of capsules on the main stem (rp = 0.80; rg = 0.85), primary branches (rp = 0.66; rg = 0.66), and capsules per plant (rp = 0.90; rg = 0.91). In contrast, a negative correlation (P < 0.001) was observed between yield and bacterial blight disease severity, both phenotypically (rp = −0.60) and genotypically (rg = −0.76). The analysis of path coefficients indicated that the most substantial positive direct effect on yield (0.77) was attributed to capsules per plant, whereas other traits associated with yield exhibited a significant indirect influence on yield through capsules per plant. Qualitative traits exhibited diversity, except for plant growth type, plant growth habit, and stem branching. Shannon-Weaner (H) and Simpson (1-D) diversity indices were higher for interior corolla color (H = 1.63; 1-D = 0.66), seed color (H = 1.50; 1-D = 0.46), and capsule beak type (H = 1.08; 1-D = 0.50). The analysis of variance indicated a notable variation among the examined genotypes regarding quantitative traits, excluding internode length. The plant materials were divided into five clusters through cluster analysis, where clusters I to V consisted of 21, 29, 4, 4, and 6 genotypes, respectively. The current study has shown that the yield of sesame can be enhanced through indirect selection for traits associated with yield, particularly the highest number of capsules per plant. Furthermore, examinations of genetic diversity confirmed the presence of variability within the assessed genotypes, providing valuable insights for upcoming sesame breeding programs.

Studies on character association and path coefficient analysis for various qualitative and quantitative traits in bottle gourd (Lagenaria siceraria (Mol.) Standl.)

Studies on character association and path coefficient analysis for various qualitative and quantitative traits in bottle gourd (Lagenaria siceraria (Mol.) Standl.)

Expression and association of quantitative traits of wheat ( Triticum aestivum L.) genotypes under different wheat growing environments

Expression and association of quantitative traits of wheat ( <i>Triticum aestivum</i> L.) genotypes under different wheat growing environments

Population-specific and cross-ancestry genome-wide association study identifies shared genetic architecture and 6 new risk loci including CAMK2D associated for Brugada syndrome

Abstract Introduction The Brugada syndrome (BrS) is an inherited arrhythmia characterized by coved-type ST-segment elevation in the right precordial leads and an increased risk for sudden cardiac death. Genome-wide association studies (GWAS) of BrS, mainly performed in European ancestry, have illustrated its complex genetic architecture as an polygenic disease besides a monogenic trait due to mutations in the major responsible cardiac sodium channel gene SCN5A. Clinical manifestations of BrS including the disease prevalence and the incidence of sudden death are known to be variable between Asian and European populations, however, its underlying mechanisms are largely unknown. Objectives We aimed to identify novel BrS-associated loci and to assess ancestry-dependent genetic heterogeneity that may underlie the variable clinical manifestations of BrS patients across different populations. Methods We performed a genome-wide meta-analysis of BrS in the Japanese ancestry (940 cases and 1,634 controls), followed by a cross-ancestry meta-analysis of Japanese and European GWAS (total of 3,760 cases and 11,635 controls) to identify novel risk loci and compared the allelic effects between two ancestries. We characterized the novel loci based on fine-mapping of potential causal variants, and expression and splicing quantitative trait associations using the Genotype-Tissue Expression (GTEx) database. Results The Japanese-specific genome-wide meta-analysis identified a novel association signal near the ZSCAN20 (lead variant, rs2336244; P=1.0E-08) besides previously reported 4 association signals at the SCN5A-SCN10A and HEY2 loci. Cross-ancestry genome-wide meta-analysis identified 17 association signals including 6 novel loci. The effect directions were consistent for 94.1% of the variants (16 of 17; P for sign test = 0.00027) and their allelic effects were highly correlated across ancestries (Pearson’s R=0.91 [P=2.9E-07]). The genetic risk score (GRS) derived from European-ancestry GWAS of BrS was significantly associated with the risk of BrS in the Japanese populations (odds ratio, 2.12 [95% confidence interval, 1.94–2.31]; P=1.2E-61), suggesting the shared genetic architecture across ancestries. The functional characterization of the 6 novel loci showed that one lead SNP on CAMK2D promotes an alternative splicing resulting in an isoform switch of calmodulin kinase II that favors up-regulation of the pro-inflammatory isoform δ9 and down-regulation of the pro-survival isoform δ3. Conclusions Our results identified 6 novel susceptible loci associated with BrS and revealed shared genetic architecture across ancestries.GWAS Manhattan plotShared genetic architecture

De novo genome assembly and analyses of 12 founder inbred lines provide insights into maize heterosis.

Hybrid maize displays superior heterosis and contributes over 30% of total worldwide cereal production. However, the molecular mechanisms of heterosis remain obscure. Here we show that structural variants (SVs) between the parental lines have a predominant role underpinning maize heterosis. De novo assembly and analyses of 12 maize founder inbred lines (FILs) reveal abundant genetic variations among these FILs and, through expression quantitative trait loci and association analyses, we identify several SVs contributing to genomic and phenotypic differentiations of various heterotic groups. Using a set of 91 diallel-cross F1 hybrids, we found strong positive correlations between better-parent heterosis of the F1 hybrids and the numbers of SVs between the parental lines, providing concrete genomic support for a prevalent role of genetic complementation underlying heterosis. Further, we document evidence that SVs in both ZAR1 and ZmACO2 contribute to yield heterosis in an overdominance fashion. Our results should promote genomics-based breeding of hybrid maize.

Epigenome-wide association study of serum folate in maternal peripheral blood leukocytes.

Aim: To perform an epigenome-wide association study (EWAS) of serum folate in maternal blood. Methods: Cross-ancestry (Europeans=302, South Asians=161) and ancestry-specific EWAS in the EPIPREG cohort were performed, followed by methyl quantitative trait loci analysis and association with cardiometabolic phenotypes. Replication was attempted using maternal folate intake and blood methylation data from theMoBa study and verified if the findings were significant in a previous EWAS of maternal serum folate in cord blood. Results & conclusion: cg19888088 (cross-ancestry) in EBF3, cg01952260 (Europeans) and cg07077240 (South Asians) in HERC3 were associated with serum folate. cg19888088 and cg01952260 were associated with diastolic blood pressure. cg07077240 was associated with variants in CASC15. The findings were not replicated and were not significant in cord blood.

Studies on character association and path coefficient for quantitative traits to yield and its attributes in garlic

Association between characters and path analysis in seventeen genotypes/lines of garlic (Allium sativum L.) was studied at the Vegetable Research Farm, BUAT, Banda during 2019 and 2020. The pooled data of correlation studies, revealed that gross yield plot-1 had positive and significant correlation with equatorial bulb diameter, weight of 20 bulbs and weight of 50 cloves at genotypic and phenotypic level respectively. This showed that improving these features could improve the crop’s physiological capacity to mobilise and translocate photosynthates to economically valuable organs (the bulb), perhaps increasing bulb yield as seen in the study. Yield was significantly and negatively correlated with bulb shape index, number of cloves bulb-1, and thrips plant-1 at genotypic level. The genotypic path coefficient analysis showed that equatorial bulb diameter and plant height had the highest positive direct effect on bulb yield. Weight of 20 bulbs and collar thickness had negative direct effect on bulb yield. Positive direct effect of equatorial bulb diameter and plant height indicated good scope for improvement in bulb yield by selecting genotypes having bigger bulb along with increased plant height.

Studies on genetic variability, heritability, genetic advance and character association for various quantitative traits in bottle gourd [Lagenaria siceraria (Mol.) Standl.] genotypes

Thirty-sevendiverse genotypes of bottle gourdwere evaluated to access the relative performance, genetic variability, heritability, genetic advance and simultaneously to study the nature and magnitude of associations between yield and its contributing characters. The genotypes were sown under RBD in three replications at Vegetable Research Farm, CCS Haryana Agricultural University, Hisar during the Spring Summer season of 2017-18. Results attained from analysis of variance reportedthat there were substantial differences among the genotypes unveiling the plausible presence of significant genetic variability, which could be positively exploited in crop improvement programmes. The highest GCV (18.90) and PCV (18.96) were observed for vine length. In addition to this, fruit yield was found significantly and positively correlated with number of fruits per vine, number of primary branches per vine and average fruit weight. The path analysis indicated that the days to first female flowering, number of fruits per vine, nodes to first female flower, length of fruit and average fruit weight were the most propitious characters directly influencing the dependent variable viz. fruit yield/ha

Comparative Analysis of Multiple GWAS Results Identifies Metabolic Pathways Associated with Resistance to A. flavus Infection and Aflatoxin Accumulation in Maize.

Aflatoxins are carcinogenic secondary metabolites produced by several species of Aspergillus, including Aspergillus flavus, an important ear rot pathogen in maize. Most commercial corn hybrids are susceptible to infection by A. flavus, and aflatoxin contaminated grain causes economic damage to farmers. The creation of inbred lines resistant to Aspergillus fungal infection or the accumulation of aflatoxins would be aided by knowing the pertinent alleles and metabolites associated with resistance in corn lines. Multiple Quantitative Trait Loci (QTL) and association mapping studies have uncovered several dozen potential genes, but each with a small effect on resistance. Metabolic pathway analysis, using the Pathway Association Study Tool (PAST), was performed on aflatoxin accumulation resistance using data from four Genome-wide Association Studies (GWAS). The present research compares the outputs of these pathway analyses and seeks common metabolic mechanisms underlying each. Genes, pathways, metabolites, and mechanisms highlighted here can contribute to improving phenotypic selection of resistant lines via measurement of more specific and highly heritable resistance-related traits and genetic gain via marker assisted or genomic selection with multiple SNPs linked to resistance-related pathways.

Identifying Quantitative Trait Loci for Thousand Grain Weight in Eggplant by Genome Re-Sequencing Analysis.

Eggplant (Solanum melongena L.; 2n = 24) is one of the most important Solanaceae vegetables and is primarily cultivated in China (approximately 42% of world production) and India (approximately 39%). Thousand-grain weight (TGW) is an important trait that affects eggplant breeding cost and variety promotion. This trait is controlled by quantitative trait loci (QTLs); however, no quantitative trait loci (QTL) has been reported for TGW in eggplant so far, and its potential genetic basis remain unclear. In this study, two eggplant lines, 17C01 (P1, wild resource, small seed) and 17C02 (P2, cultivar, large seed), were crossed to develop F1, F2 (308 lines), BC1P1 (44 lines), and BC1P2 (44 lines) populations for quantitative trait association analysis. The TGWs of P1, P2 and F1 were determined as 3.00, 3.98 and 3.77 g, respectively. The PG-ADI (polygene-controlled additive-dominance-epistasis) genetic model was identified as the optimal model for TGW and the polygene heritability value in the F2 generation was as high as 80.87%. A high-quality genetic linkage bin map was constructed with resequencing analysis. The map contained 3,918 recombination bins on 12 chromosomes, and the total length was 1,384.62 cM. A major QTL (named as TGW9.1) located on chromosome 9 was identified to be strongly associated with eggplant TGW, with a phenotypic variance explanation of 20.51%. A total of 45 annotated genes were identified in the genetic region of TGW9.1. Based on the annotation of Eggplant genome V3 and orthologous genes in Arabidopsis thaliana, one candidate gene SMEL_009g329850 (SmGTS1, encoding a putative ubiquitin ligase) contains 4 SNPs and 2 Indels consecutive intron mutations in the flank of the same exon in P1. SmGTS1 displayed significantly higher expression in P1 and was selected as a potential candidate gene controlling TGW in eggplant. The present results contribute to shed light on the genetic basis of the traits exploitable in future eggplant marker-assisted selection (MAS) breeding.

COL18A1 genotypic associations with endostatin levels and clinical features in pulmonary arterial hypertension: a quantitative trait association study.

Variation around the COL18A1 gene, which encodes the angiostatic peptide endostatin, may influence disease heterogeneity in pulmonary arterial hypertension https://bit.ly/3shXrNR

Genome wide copy number variations using Porcine 60K SNP Beadchip in Landlly pigs

In the present study, Porcine 60K SNP genotype data from 69 Landlly pigs were used to explore Copy Number Variations (CNVs) across the autosomes. A total of 386 CNVs were identified using Hidden Markov Model (HMM) in PennCNV software, which were subsequently aggregated to 115 CNV regions (CNVRs). Among the total detected CNVRs, 58 gain, 49 were loss type while remaining 8 events were both gain and loss types. Identified CNVRs covered 12.5 Mb (0.55%) of Sus scrofa reference 11.1 genome. Comparison of our results with previous investigations on pigs revealed that approximately 75% CNVRs were novel, which may be due to differences in genetic background, environment and implementation of artificial selection in Landlly pigs. Functional annotation and pathway analysis showed the significant enrichment of 267 well-annotated Sus scrofa genes in CNVRs. These genes were involved in different biological functions like sensory perception, meat quality traits, back fat thickness and immunity. Additionally, KIT and FUT1 were two major genes detected on CNVR in our population. This investigation provided a comprehensive overview of CNV distribution in the Indian porcine genome for the first time, which may be useful for further investigating the association of important quantitative traits in Landlly pigs. Highlights 115 CNVRs were identified in 69 Landlly pig population. Approximately 75% detected CNVRs were novel for Landlly population. Significant enrichment of 267 well-annotated Sus scrofa genes observed in these CNVRs. These genes were involved in different biological functions like sensory perception, meat quality traits, back fat thickness and immunity. Comprehensive CNV map in the Indian porcine genome developed for the first time.

Gene Region Association Analysis of Longitudinal Quantitative Traits Based on a Function-On-Function Regression Model.

In the process of growth and development in life, gene expressions that control quantitative traits will turn on or off with time. Studies of longitudinal traits are of great significance in revealing the genetic mechanism of biological development. With the development of ultra-high-density sequencing technology, the associated analysis has tremendous challenges to statistical methods. In this paper, a longitudinal functional data association test (LFDAT) method is proposed based on the function-on-function regression model. LFDAT can simultaneously treat phenotypic traits and marker information as continuum variables and analyze the association of longitudinal quantitative traits and gene regions. Simulation studies showed that: 1) LFDAT performs well for both linkage equilibrium simulation and linkage disequilibrium simulation, 2) LFDAT has better performance for gene regions (include common variants, low-frequency variants, rare variants and mixture), and 3) LFDAT can accurately identify gene switching in the growth and development stage. The longitudinal data of the Oryza sativa projected shoot area is analyzed by LFDAT. It showed that there is the advantage of quick calculations. Further, an association analysis was conducted between longitudinal traits and gene regions by integrating the micro effects of multiple related variants and using the information of the entire gene region. LFDAT provides a feasible method for studying the formation and expression of longitudinal traits.

Construction of Genetic Linkage Maps From a Hybrid Family of Large Yellow Croaker (Larimichthys crocea).

Consensus and sex-specific genetic linkage maps for large yellow croaker (Larimichthys crocea) were constructed using samples from an F1 family produced by crossing a Daiqu female and a Mindong male. A total of 20,147 single nucleotide polymorphisms (SNPs) by restriction site associated DNA sequencing were assigned to 24 linkage groups (LGs). The total length of the consensus map was 1757.4 centimorgan (cM) with an average marker interval of 0.09 cM. The total length of female and male linkage map was 1533.1 cM and 1279.2 cM, respectively. The average female-to-male map length ratio was 1.2 ± 0.23. Collapsed markers in the genetic maps were re-ordered according to their relative positions in the ASM435267v1 genome assembly to produce integrated genetic linkage maps with 9885 SNPs distributed across the 24 LGs. The recombination pattern of most LGs showed sigmoidal patterns of recombination, with higher recombination in the middle and suppressed recombination at both ends, which corresponds with the presence of sub-telocentric and acrocentric chromosomes in the species. The average recombination rate in the integrated female and male maps was respectively 3.55 cM/Mb and 3.05 cM/Mb. In most LGs, higher recombination rates were found in the integrated female map, compared to the male map, except in LG12, LG16, LG21, LG22, and LG24. Recombination rate profiles within each LG differed between the male and the female, with distinct regions indicating potential recombination hotspots. Separate quantitative trait loci (QTL) and association analyses for growth related traits in 6 months fish were performed, however, no significant QTL was detected. The study indicates that there may be genetic differences between the two strains, which may have implications for the application of DNA-information in the further breeding schemes.

Study of Genetic Variability, Character Association and Genetic Diversity Analysis for Quantitative Traits in Winged Bean (Psophocarpus Tetragonolobus L)

Study of Genetic Variability, Character Association and Genetic Diversity Analysis for Quantitative Traits in Winged Bean (Psophocarpus Tetragonolobus L)

Genetic Variability, Heritability and Association of Quantitative Traits in Maize (Zea mays L) Genotypes: Review Paper

Genetic Variability, Heritability and Association of Quantitative Traits in Maize (Zea mays L) Genotypes: Review Paper

Character association and path analysis of quantitative traits among marigold (Tagetes sp.) genotypes

The path-coefficient analysis provides information about direct and indirect effect of other morphological characteristics on flower yield per plant, hence this investigation was undertaken to study the effects of various quantitative traits among marigold (Tagetes sp.) genotypes. The genetic variability and heritability in 21 genotypes of marigold confirmed that there is a colossal difference between the genotypes for yield and other 17 traits. The number of ray florets/ flower showed high heritability (99.95) together with high genetic advance (255.77) followed by fresh weight of flower and yield per plant. The study revealed that the PCV is more in comparison with GCV for all the traits which indicates, the contribution of the environment in the expression of traits. Correlation analysis between yield and yield attributing traits in marigold genotypes revealed high positive correlation of flower yield per plant at both phenotypic and genotypic levels with traits like plant height, plant spread, number of primary branches per plant, stem diameter, number of leaves per plant, fresh weight of flower, flower diameter, number of ray florets per flower and flowering duration. Path analysis revealed that the characters like fresh weight of flower and number of flowers per plant are important characters affecting flower yield since they had high direct positive effect. The magnitude of genetic divergence of marigold collected from four different states of India showed the presence of wide genetic diversity. Characters of maximum association with yield have been identified and a selection programme based on the above traits shall be highly effective in improving flower yield of marigold.

Variability and Character Association for Yield and Quantitative Traits under Late Sown Conditions in Chickpea (Cicer arietinum L.)

Background: Among all the pulses, chickpea is the most important rabi crop with high acceptability and wider use in India. More availability of quality seed of improved varieties being made available to the famers is one of the most important factors contributing to better harvest of chickpea in recent years. Therefore, there is urgent need for developing high yielding varieties of chickpea employing sound and effective breeding strategies. The study of variability, correlation and path coefficient analysis for seed yield with other yield contributing characters is of immense importance to get information regarding exercising selections for genetic improvement in chickpea.Methods: A total of 40 genotypes of chickpea were undertaken for present study and these genotypes evaluated in randomized block design (RBD) with three replications at Rajasthan Agricultural Research Institute (SKNAU), Jaipur Rajasthan, India under late sown conditions during rabi 2019-20. The experimental unit was four row plots of 4 m long and spacing between row to row was kept to 30 cm and plant to plant was 10 cm. The genetic parameters viz., mean GCV, PCV, broad sense heritability, genetic advance (GA), correlation coefficient and path analysis were estimated.Result: Genotypes revealed significant wide genetic variation for almost all the quantitative traits. Number of pods plant-1 exhibited highest PCV and GCV. The highest broad sense heritability (h2b) was recorded for days to maturity followed by days to 50% flowering and 100-seed weight. The 100-seed weight, number of pods plant-1, number of seeds pod-1 and primary branches plant-1 had positive genotypic correlation with grain yield. Path coefficient analysis depicted that among the 9 causal (independent) traits; number of seeds pod-1, number of pods plant-1, number of primary branches plant-1, plant height from ground to first pod (cm) and days to 50% flowering had positive and directly influence on grain yield. Therefore these traits can be taken into consideration while exercising selection for grain yield in chickpea.