Genome-wide Analysis Study Research Articles

Investigating causality and shared genetic architecture between body mass index and cognitive function: a genome-wide cross-trait analysis and bi-directional Mendelian randomization study.

Observational studies have established a connection between body mass index (BMI) and an increased risk of cognitive decline. However, a comprehensive investigation into the causal relationships between BMI and cognitive function across diverse age groups, as well as the genetic underpinnings of this relationship, has been notably lacking. This study aims to investigate causality and the shared genetic underpinnings of between BMI and cognitive function by conducting a thorough genome-wide analysis, thereby provide valuable insights for developing personalized intervention strategies to promote cognitive health. Genetic associations between BMI and cognitive function were thoroughly investigated through covariate genetic analysis and chained imbalance score regression, utilizing data from genome-wide association studies (GWAS). Bi-directional Mendelian Randomization (MR) was employed to uncover associations and potential functional genes were further scrutinized through Cross-trait meta-analysis and Summary-data-based MR (SMR). Subsequently, a detailed examination of the expression profiles of the identified risk SNPs in tissues and cells was conducted. The study found a significant negative correlation between BMI and cognitive function (β = -0.16, P = 1.76E-05), suggesting a causal linkage where higher BMI values were predictive of cognitive impairment. We identified 5 genetic loci (rs6809216, rs7187776, rs11713193, rs13096480, and rs13107325) between BMI and cognitive function by cross-trait meta-analysis and 5 gene-tissue pairs were identified by SMR analysis. Moreover, two novel risk genes TUFM and MST1R were shared by both cross-trait analysis and SMR analysis, which had not been observed in previous studies. Furthermore, significant enrichment of single nucleotide polymorphisms (SNPs) at tissue- and cell-specific levels was identified for both BMI and cognitive function, predominantly within the brain. This study uncovers a causal relationship between BMI and cognitive function, with the discovery of TUFM and MST1R as shared genetic factors associated with both conditions. This novel finding offers new insights into the development of preventative strategies for cognitive decline in obese individuals, and further enhances our understanding of the underlying pathophysiology of these conditions. Furthermore, these findings could serve as a guide for the development of innovative therapeutic approaches to address cognitive decline in obese individuals.

Mediating function of heart failure in the causal relationship between diastolic blood pressure and hypertensive renal disease with renal failure: a mediated Mendelian randomization study†

Abstract Objective To study the causality relationship between diastolic blood pressure (DBP) and hypertensive renal disease with renal failure (HRDRF) and the mediating role of heart failure (HF) in the causality relationship by network Mendelian randomization (MR). Methods Genome-wide analysis of DBP, HRDRF, and HF was downloaded from the public database (Genome-Wide Analysis Study [GWAS]) and was used to analyze the results and to conduct mediated MR analysis. Results Analysis showed that DBP was positively correlated with HRDRF (OR = 1.0002, 95% CI: 1.0001–1.0003, P = 1.8076e–05) and DBP was positively correlated with HF (OR = 1.0295, 95% CI: 1.0221–1.0370, P = 2.5292e–15). HF and HRDRF had a positive causal effect (OR = 1.0001, 95% CI: 1.0000–1.0001, P = 0.0152). Mediation analysis showed that the contribution ratio of HF to the combined effect of DBP and HRDRF was 24.69%. Conclusions DBP can increase the risk of renal disease with renal failure, and HF may play an important role in mediating this causal relationship.

GWAS in interaction with childhood traumas implicates novel variants and genes previously associated with suicide-related factors in the background of suicidal ideation

IntroductionAlthough suicide claims more lives than war and homicide, we still have no sufficient and effective methods either for its prediction or for its prevention. Our screening methods are laborous and subjective both on the side of the patient and on the side of the clinician. Understanding the genetic background of suicidal behaviour would help identify biomarkers for screening as well as pathways as potential targets for novel intervention and prevention approaches. However, in spite of a number of GWAS studies, results are few and rarely replicate, and generally accurate phenotyping and sufficient consideration of environmental stressors is also missing.ObjectivesIn our present study we performed a genome-wide analysis study for suicidal ideation in interaction with early childhood traumas in a deep-phenotyped general population sample.MethodsOur analysis used data from 1800 volunteers in the NewMood project. As outcome phenotype the suicidal ideation item of the Brief Symptom Inventory was used. A modified version of the Childhood Trauma Questionnaire was used to assess early adverse experiences. A genome-wide association analysis was performed with Plink 1.9, including a total of 3,474,641 variants after quality control steps, followed by genome-wide by environment interaction analyses. Our models included control variables for sex, age, and the top 10 genomic principal components. Functional annotation of SNPs was carried out using FUMA v1.5.6, gene-based tests were performed using MAGMA v1.08.Results7 SNPs met suggestive significance in main effect analyses, of which 2 reached genome-wide significance including rs79912020 (p=3.21E-10, β=0.746) and rs10236520 (p=1.71E-08, β=0.484), with no significant findings in gene-based tests. Interaction analyses with childhood adversities yielded 31 SNPs that met genome-wide significance, including rs7983955 (p=2.28E-11, β=0.182), rs141039461 (p=3.90E-11, β=0.0541), rs12692827 (p=3.69E-10, β=0.0612) as the top SNPs. In interaction with childhood adversities, 31 genes showed a significant association in gene-based tests, including RBFOX1 (p=1.09E-10), GRM7 (p=1.20E-10), MTCH1 (p=5.59E-09), and CDH13 (p=6.60E-09) as the most significant findings.ConclusionsOur results indicate several important novel SNPs associated with suicidal ideation when considered in interaction with the effect of childhood adversities. Furthermore, gene-based analyses replicate several genes playing a key role in central nervous system function such as GRM7 (encoding metabotropic glutamate receptor 7) or previously implicated in association with suicide (CDH13) or suicide-related factors such as aggression (RBFOX1).Funding: NAP2022-I-4/2022, K143391, 2019-2.1.7-ERA-NET-2020-00005, TKP2021-EGA-25Disclosure of InterestNone Declared

Genome wide characterization and expression analysis of CrRLK1L gene family in wheat unravels their roles in development and stress-specific responses.

Catharanthus roseus receptor-like kinase 1-like (CrRLK1L) genes encode a subfamily of receptor-like kinases (RLK) that regulate diverse processes during plant growth, development, and stress responses. The first CrRLK1L was identified from the Catharanthus roseus, commonly known as Madagascar periwinkle. Subsequently, CrRLK1L gene families have been characterized in many plants. The genome of T. aestivum encodes 15 CrRLK1L genes with 43 paralogous copies, with three homeologs each, except for -2-D and -7-A, which are absent. Chromosomal localization analysis revealed a markedly uneven distribution of CrRLK1L genes across seven different chromosomes, with chromosome 4 housing the highest number of genes, while chromosome 6 lacked any CrRLK1L genes. Tissue-specific gene expression analysis revealed distinct expression patterns among the gene family members, with certain members exhibiting increased expression in reproductive tissues. Gene expression analysis in response to various abiotic and biotic stress conditions unveiled differential regulation of gene family members. Cold stress induces CrRLK1Ls -4-B and -15-A while downregulating -3-A and -7B. Drought stress upregulates -9D, contrasting with the downregulation of -7D. CrRLK1L-15-B and -15-D were highly induced in response to 1 hr of heat, and combined drought and heat stress, whereas -10-B is downregulated. Similarly, in response to NaCl stress, only CrRLK1L1 homeologs were induced. Fusarium graminearum and Claviceps purpurea inoculation induces homeologs of CrRLK1L-6 and -7. The analysis of cis-acting elements in the promoter regions identified elements crucial for plant growth and developmental processes. This comprehensive genome-wide analysis and expression study provides valuable insights into the essential functions of CrRLK1L members in wheat.

Genome-wide analysis of NPR1-like genes in citrus species and expression analysis in response to citrus canker (Xanthomonas axonopodis pv. citri).

Citrus fruits, revered for their nutritional value, face significant threats from diseases like citrus canker, particularly impacting global citrus cultivation, notably in Pakistan. This study delves into the critical role of NPR1-like genes, the true receptors for salicylic acid (SA), in the defense mechanisms of citrus against Xanthomonas axonopodis pv. citri (Xcc). By conducting a comprehensive genome-wide analysis and phylogenetic study, the evolutionary dynamics of Citrus limon genes across diverse citrus cultivars are elucidated. Structural predictions unveil conserved domains, such as the BTB domain and ankyrin repeat domains, crucial for the defense mechanism. Motif analysis reveals essential conserved patterns, while cis-regulatory elements indicate their involvement in transcription, growth, response to phytohormones, and stress. The predominantly cytoplasmic and nuclear localization of NPR1-like genes underscores their pivotal role in conferring resistance to various citrus species. Analysis of the Ks/Ka ratio indicates a purifying selection of NPR1-like genes, emphasizing their importance in different species. Synteny and chromosomal mapping provide insights into duplication events and orthologous links among citrus species. Notably, Xac infection stimulates the expression of NPR1-like genes, revealing their responsiveness to pathogenic challenges. Interestingly, qRT-PCR profiling post-Xac infection reveals cultivar-specific alterations in expression within susceptible and resistant citrus varieties. Beyond genetic factors, physiological parameters like peroxidase, total soluble protein, and secondary metabolites respond to SA-dependent PR genes, influencing plant characteristics. Examining the impact of defense genes (NPR1) and plant characteristics on disease resistance in citrus, this study marks the inaugural investigation into the correlation between NPR1-associated genes and various plant traits in both susceptible and resistant citrus varieties to citrus bacterial canker.

Genetic parameter estimation and molecular foundation of chicken egg-laying trait

The age of first egg (AFE) in chicken can affect early and even life-time egg production performance to some extent, and therefore is an important economic trait that affects production efficiency. To better understand the genetic patterns of AFE and other production traits including body weight at first egg (BWA), first egg weight (FEW), and total egg number from AFE to 58 wk of age (total-EN), we recorded the production performance of 2 widely used layer breeds, white leghorn (WL) and Rhode Island Red (RIR) and estimated genetic parameters based on pedigree and production data. The results showed that the heritability of AFE in both breeds ranged from 0.4 to 0.6, and AFE showed strong positive genetic and phenotypic correlations to BWA as well as FEW, while showing strong negative genetic and phenotypic correlations with total-EN. Furtherly, by genome-wide association analysis study (GWAS), we identified 12 and 26 significant SNPs to be related to AFE in the 2-layer breeds, respectively. A total of 18 genes were identified that could affect AFE based on the significant SNP annotations obtained, but there were no gene overlapped in the 2 breeds indicating the genetic foundation of AFE could differ from breed to breed. Our results provided a deeper understanding of genetic patterns and molecular basement of AFE in different breeds and could help in the selection of egg production traits.

Isolation and identification, genome-wide analysis and pathogenicity study of a novel PRRSV-1 in southern China.

Porcine reproductive and respiratory syndrome virus (PRRSV) has caused severe economic losses to the global swine industry. In recent years, the incidence of PRRSV-1 has been gradually increasing in China, but there are still few studies on it. In this study, clinical samples for PRRS virus isolation were collected from a pig farm in South China in 2022. We effectively isolated a strain of PRRSV utilizing PAM cells and demonstrated its consistent transmission capability on Marc-145 cells. The isolated strain was confirmed as PRRSV-1 by RT-qPCR, IFA, electron microscopy, etiolated spot purification and whole genome sequencing, the strain was named GD2022. The length of GD2022 genome is 15058nt; Based on the genome-wide genetic evolutionary analysis of GD2022, the strain was classified as PRRSV-1. Further genetic evolutionary analysis of its ORF5 gene showed that GD2022 belonged to PRRSV-1 subtype 1 and formed an independent branch in the evolutionary tree. Compared with the sequence of the classical PRRSV-1 strain (LV strain), GD2022 has several amino acid site mutations in the antigenic region from GP3 to GP5, these mutations are different from those of other PRRSV-1 strains in China. Recombination analysis showed no recombination events with GD2022. In addition, piglets infected with GD2022 displayed clinical respiratory symptoms and typical pathological changes. In this study, a strain of the PRRSV-1 virus was isolated using both PAM cells and Marc-145 and proved to be pathogenic to piglets, providing an important reference for the identification, prevention, and control of PRRSV-1.

Genome-wide analysis study of gestational diabetes mellitus and related pathogenic factors in a Chinese Han population

BackgroundGestational diabetes mellitus (GDM) affects the metabolism of both the mother and fetus during and after pregnancy. Genetic factors are important in the pathogenesis of GDM, and associations vary by ethnicity. However, related studies about the relationship between the susceptibility genes and glucose traits remain limited in China. This study aimed to identify genes associated with GDM susceptibility in Chinese Han women and validate those findings using clinical data during pregnancy and postpartum period.MethodsA genome-wide association study (GWAS) of 398 Chinese Han women (199 each with and without GDM) was conducted and associations between single nucleotide polymorphisms (SNPs) and glucose metabolism were identified by searching public databases. Relationships between filtered differential SNPs and glucose metabolism were verified using clinical data during pregnancy. The GDM group were followed up postpartum to evaluate the progression of glucose metabolism.ResultsWe identified five novel SNPs with genome-wide significant associations with GDM: rs62069863 in TRPV3 gene and rs2232016 in PRMT6 gene were positive correlated with 1 h plasma glucose (1hPG) and 2 h plasma glucose (2hPG), rs1112718 in HHEX/EXOC6 gene and rs10460009 in LPIN2 gene were positive associated with fasting plasma glucose, 1hPG and 2hPG, rs927316 in GLIS3 gene was negative correlated with 2hPG. Of the 166 GDM women followed up postpartum, rs62069863 in TRPV3 gene was positively associated with fasting insulin, homoeostasis model assessment of insulin resistance.ConclusionsThe variants of rs62069863 in TRPV3 gene, rs2232016 in PRMT6 gene, rs1112718 in HHEX/EXOC6 gene, rs927316 in GLIS3 gene, and rs10460009 in LPIN2 gene were newly-identified susceptibility loci for GDM in the Chinese Han population. TRPV3 was associated with worse insulin resistance postpartum.Trial registrationThis study was registered in the Chinese Clinical Trial Registry. Trial registration number: ChiCTR2100043762. Date of first registration: 28/02/2021.

Genome-wide identification, expression analysis, and functional study of the bZIP transcription factor family and its response to hormone treatments in pea (Pisum sativum L.)

BackgroundBasic leucine zipper (bZIP) protein is a plant-specific transcription factor involved in various biological processes, including light signaling, seed maturation, flower development, cell elongation, seed accumulation protein, and abiotic and biological stress responses. However, little is known about the pea bZIP family.ResultsIn this study, we identified 87 bZIP genes in pea, named PsbZIP1 ~ PsbZIP87, via homology analysis using Arabidopsis. The genes were divided into 12 subfamilies and distributed unevenly in 7 pea chromosomes. PsbZIPs in the same subfamily contained similar intron/exon organization and motif composition. 1 tandem repeat event and 12 segmental duplication events regulated the expansion of the PsbZIP gene family. To better understand the evolution of the PsbZIP gene family, we conducted collinearity analysis using Arabidopsis thaliana, Oryza sativa Japonica, Fagopyrum tataricum, Solanum lycopersicum, Vitis vinifera, and Brachypodium distachyon as the related species of pea. In addition, interactions between PsbZIP proteins and promoters containing hormone- and stress-responsive cis-acting elements suggest that the regulation of PsbZIP expression was complex. We also evaluated the expression patterns of bZIP genes in different tissues and at different fruit development stages, all while subjecting them to five hormonal treatments.ConclusionThese results provide a deeper understanding of PsbZIP gene family evolution and resources for the molecular breeding of pea. The findings suggested that PsbZIP genes, specifically PSbZIP49, play key roles in the development of peas and their response to various hormones.

Genetic diversity, population structure, and genome-wide association analysis of ginkgo cultivars.

Ginkgo biloba is an economically valuable tree worldwide. The species has nearly become extinct during the Quaternary, which has likely resulted in reduction of its genetic variability. The genetic variability is now conserved in few natural populations in China and a number of cultivars that are, however, derived from a few ancient trees, helping the species survive in China through medieval times. Despite the recent interest in ginkgo, however, detailed knowledge of its genetic diversity, conserved in cultivated trees and cultivars, has remained poor. This limits efficient conservation of its diversity as well as efficient use of the existing germplasm resources. Here we performed genotyping-by-sequencing (GBS) on 102 cultivated germplasms of ginkgo collected to explore their genetic structure, kinship, and inbreeding prediction. For the first time in ginkgo, a genome-wide association analysis study (GWAS) was used to attempt gene mapping of seed traits. The results showed that most of the germplasms did not show any obvious genetic relationship. The size of the ginkgo germplasm population expanded significantly around 1500years ago during the Sui and Tang dynasties. Classification of seed cultivars based on a phylogenetic perspective does not support the current classification criteria based on phenotype. Twenty-four candidate genes were localized after performing GWAS on the seed traits. Overall, this study reveals the genetic basis of ginkgo seed traits and provides insights into its cultivation history. These findings will facilitate the conservation and utilization of the domesticated germplasms of this living fossil plant.

Genetic factors for differentiated thyroid cancer in French Polynesia: new candidate loci.

Populations of French Polynesia (FP), where France performed atmospheric tests between 1966 and 1974, experience a high incidence of differentiated thyroid cancer (DTC). However, up to now, no sufficiently large study of DTC genetic factors in this population has been performed to reach definitive conclusion. This research aimed to analyze the genetic factors of DTC risk among the native FP populations. We analyzed more than 300000 single nucleotide polymorphisms (SNPs) genotyped in 283 DTC cases and 418 matched controls born in FP, most being younger than 15 years old at the time of the first nuclear tests. We analyzed the genetic profile of our cohort to identify population subgroups. We then completed a genome-wide analysis study on the whole population. We identified a specific genetic structure in the FP population reflecting admixture from Asian and European populations. We identified three regions associated with increased DTC risk at 6q24.3, 10p12.2, and 17q21.32. The lead SNPs at these loci showed respective p-values of 1.66×10-7, 2.39×10-7, and 7.19×10-7 and corresponding odds ratios of 2.02, 1.89, and 2.37. Our study results suggest a role of the loci 6q24.3, 10p12.2 and 17q21.32 in DTC risk. However, a whole genome sequencing approach would be better suited to characterize these factors than genotyping with microarray chip designed for the Caucasian population. Moreover, the functional impact of these three new loci needs to be further explored and validated.

Genetic expression and immunofluorescence mapping of NaV1 highlight potential therapeutic targets in anti-inflammatory treatment of aortic valves stenosis

Background and Aims : Aortic valve stenosis (AVS) is the most prevalent heart valve disease worldwide. Despite better interventional treatment strategies, AVS is associated with a high morbidity and mortality. The aortic valve is innervated, but the neural regulation of these AVS processes is unknown. Recently, a genome wide analysis study (GWAS) associated neuron navigator 1 (NAV1) with AVS. Since NAV1 is a microtubule-associated protein involved in developmental neural migration, the aim of the study was to establish the relation of NAV1 expression to AVS disease stages and AVS pathophysiological pathways, and to map the neural NAV1 to demonstrate its possible role in guiding the valvular anti-inflammatory cholinergic pathway.

Bioinformatic Prioritization and Functional Annotation of GWAS-Based Candidate Genes for Primary Open-Angle Glaucoma.

Background: Primary open-angle glaucoma (POAG) is the most prevalent glaucoma subtype, but its exact etiology is still unknown. In this study, we aimed to prioritize the most likely ‘causal’ genes and identify functional characteristics and underlying biological pathways of POAG candidate genes. Methods: We used the results of a large POAG genome-wide association analysis study from GERA and UK Biobank cohorts. First, we performed systematic gene-prioritization analyses based on: (i) nearest genes; (ii) nonsynonymous single-nucleotide polymorphisms; (iii) co-regulation analysis; (iv) transcriptome-wide association studies; and (v) epigenomic data. Next, we performed functional enrichment analyses to find overrepresented functional pathways and tissues. Results: We identified 142 prioritized genes, of which 64 were novel for POAG. BICC1, AFAP1, and ABCA1 were the most highly prioritized genes based on four or more lines of evidence. The most significant pathways were related to extracellular matrix turnover, transforming growth factor-β, blood vessel development, and retinoic acid receptor signaling. Ocular tissues such as sclera and trabecular meshwork showed enrichment in prioritized gene expression (>1.5 fold). We found pleiotropy of POAG with intraocular pressure and optic-disc parameters, as well as genetic correlation with hypertension and diabetes-related eye disease. Conclusions: Our findings contribute to a better understanding of the molecular mechanisms underlying glaucoma pathogenesis and have prioritized many novel candidate genes for functional follow-up studies.

Genetic Variants Involved in the Crystallization Pathway Are Associated with Calcium Nephrolithiasis in the Chinese Han Population.

A genome-wide association analysis study (GWAS) in the Japanese population identified 14 significant loci associated with nephrolithiasis. Besides 4 novel loci related to metabolic traits, the 10 remaining loci were associated with kidney or electrolyte-related traits. We aimed to replicate the association of these loci with calcium nephrolithiasis in the Chinese Han population. A case–control association analysis was conducted involving 691 calcium nephrolithiasis patients and 1008 control subjects. We were able to genotype a total of 11 single-nucleotide polymorphisms (SNPs) previously identified as being correlated with nephrolithiasis in the Japanese population. SNP rs35747824 at PDILT was related to calcium nephrolithiasis in the Chinese Han population (p = 4.346 × 10−3, OR = 1.292). Moreover, four SNPs at four loci, rs6667242 at ALPL (p = 0.02999, OR = 0.8331), rs1544935 at KCNK5 (p = 0.01341, OR = 0.7804), rs7328064 at DGKH (p = 0.007452, OR = 1.211) and rs13041834 at BCAS1 (p = 0.03897, OR = 0.8409), were suggestively associated with calcium nephrolithiasis. Our results demonstrated that the genetic variants at 1p36.12, 6p21.2, 13q14.11, 16p12.3 and 20q13.2 are associated with calcium nephrolithiasis in the Chinese Han population. Furthermore, our study highlights the importance of genetic variance associated with the crystallization pathway in Chinese patients with calcium nephrolithiasis.

Genome-wide identification, expression analysis, and functional study of the GRAS transcription factor family and its response to abiotic stress in sorghum [Sorghum bicolor (L.) Moench

BackgroundGRAS, an important family of transcription factors, have played pivotal roles in regulating numerous intriguing biological processes in plant development and abiotic stress responses. Since the sequencing of the sorghum genome, a plethora of genetic studies were mainly focused on the genomic information. The indepth identification or genome-wide analysis of GRAS family genes, especially in Sorghum bicolor, have rarely been studied.ResultsA total of 81 SbGRAS genes were identified based on the S. bicolor genome. They were named SbGRAS01 to SbGRAS81 and grouped into 13 subfamilies (LISCL, DLT, OS19, SCL4/7, PAT1, SHR, SCL3, HAM-1, SCR, DELLA, HAM-2, LAS and OS4). SbGRAS genes are not evenly distributed on the chromosomes. According to the results of the gene and motif composition, SbGRAS members located in the same group contained analogous intron/exon and motif organizations. We found that the contribution of tandem repeats to the increase in sorghum GRAS members was slightly greater than that of fragment repeats. By quantitative (q) RT-PCR, the expression of 13 SbGRAS members in different plant tissues and in plants exposed to six abiotic stresses at the seedling stage were quantified. We further investigated the relationship between DELLA genes, GAs and grain development in S. bicolor. The paclobutrazol treatment significantly increased grain weight, and affected the expression levels of all DELLA subfamily genes. SbGRAS03 is the most sensitive to paclobutrazol treatment, but also has a high response to abiotic stresses.ConclusionsCollectively, SbGRAs play an important role in plant development and response to abiotic stress. This systematic analysis lays the foundation for further study of the functional characteristics of GRAS genes of S. bicolor.

Genome-wide analysis of Hsp70 and Hsp100 gene families in Ziziphus jujuba.

The Ziziphus species are naturally tolerant to a range of abiotic stresses. Therefore, it is expected that they are an enriched source of genes conferring stress tolerance. Heat shock proteins (Hsps) play a significant role in plants in imparting tolerance against abiotic stress conditions. To get an insight into potential Hsp function in Ziziphus, we performed a genome-wide analysis and expression study of Hsp70 and Hsp100 gene families in Ziziphus jujuba. We identified 21 and 6 genes of the ZjHsp70 and ZjHsp100 families, respectively. Physiochemical properties, chromosomal location, gene structure, motifs, and protein domain organization were analysed for structural and functional characterization. We identified the contribution of tandem and segmental gene duplications in expansions of ZjHsp70s and ZjHsp100s in Z. jujuba. Promoter analysis suggested that ZjHsp70s and ZjHsp100s perform diverse functions related to abiotic stress. Furthermore, expression analyses revealed that most of the Z. jujuba Hsp genes are differentially expressed in response to heat, drought, and salinity stress. Our analyses suggested ZjHsp70-3, ZjHsp70-5, ZjHsp70-6, ZjHsp70-16, ZjHsp70-17, ZjHsp70-20, ZjHsp100-1, ZjHsp100-2, and ZjHsp100-3 are potential candidates for further functional analysis and with regard to breeding new more resilient strains. The present analysis laid the foundation for understanding the molecular mechanism of Hsps70 and Hsp100 gene families regulating abiotic stress tolerance in Z. jujuba.

Genome-Wide Identification, Expression Analysis and Functional Study of CCT Gene Family in Medicago truncatula.

The control of flowering time has an important impact on biomass and the environmental adaption of legumes. The CCT (CO, COL and TOC1) gene family was elucidated to participate in the molecular regulation of flowering in plants. We identified 36 CCT genes in the M. truncatula genome and they were classified into three distinct subfamilies, PRR (7), COL (11) and CMF (18). Synteny and phylogenetic analyses revealed that CCT genes occurred before the differentiation of monocot and dicot, and CCT orthologous genes might have diversified among plants. The diverse spatial-temporal expression profiles indicated that MtCCT genes could be key regulators in flowering time, as well as in the development of seeds and nodules in M. truncatula. Notably, 22 MtCCT genes with typical circadian rhythmic variations suggested their different responses to light. The response to various hormones of MtCCT genes demonstrated that they participate in plant growth and development via varied hormones dependent pathways. Moreover, six MtCCT genes were dramatically induced by salinity and dehydration treatments, illustrating their vital roles in the prevention of abiotic injury. Collectively, our study provides valuable information for the in-depth investigation of the molecular mechanism of flowering time in M. truncatula, and it also provides candidate genes for alfalfa molecular breeding with ideal flowering time.

Circulating Vitamin E Levels and Risk of Coronary Artery Disease and Myocardial Infarction: A Mendelian Randomization Study.

Observational studies have reported a cardioprotective effect of vitamin E whereas intervention trials failed to confirm its beneficial effects, and even some reported adverse effects of vitamin E supplements on coronary artery disease (CAD). To clarify, we conducted a two-sample mendelian randomization study to investigate causal association of vitamin E with the risk of CAD. Three single nucleotide polymorphisms (SNPs) identified in a genome-wide analysis study including 7781 individuals of European descent, rs964184, rs2108622, and rs11057830 were used as the genetic instruments for vitamin E. Data for CAD/myocardial infarction (MI) were available from Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics consortium. The effect of each SNP on CAD/myocardial infarction (MI) was weighted by its effect on serum vitamin E (mg/L), and results were pooled to give a summary estimates for the effect of increased vitamin E on risk of CAD/MI. Based on 3 SNPs each 1 mg/L increase in vitamin E was significantly associated with CAD (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.03–1.06), MI (OR 1.04, 95% CI 1.03–1.05), elevated low-density lipoprotein cholesterol (0.021 standard deviations (SD), 95% CI 0.016, 0.027), triglycerides (0.026 SD, 95% CI 0.021, 0.031), and total cholesterol (0.043 SD, 95% CI 0.038, 0.048) and lower levels of high-density lipoprotein cholesterol (−0.019 SD 95% CI −0.024, −0.014). Our findings indicate that higher vitamin E may increase the risk of CAD/MI and the safety and efficacy of vitamin E supplementation use should be reevaluated.

A Genome-Wide Association Study of Sprint Performance in Elite Youth Football Players

Pickering, C, Suraci, B, Semenova, EA, Boulygina, EA, Kostryukova, ES, Kulemin, NA, Borisov, OV, Khabibova, SA, Larin, AK, Pavlenko, AV, Lyubaeva, EV, Popov, DV, Lysenko, EA, Vepkhvadze, TF, Lednev, EM, Leońska-Duniec, A, Pająk, B, Chycki, J, Moska, W, Lulińska-Kuklik, E, Dornowski, M, Maszczyk, A, Bradley, B, Kana-ah, A, Cięszczyk, P, Generozov, EV, and Ahmetov, II. A genome-wide association study of sprint performance in elite youth football players. J Strength Cond Res 33(9): 2344-2351, 2019-Sprint speed is an important component of football performance, with teams often placing a high value on sprint and acceleration ability. The aim of this study was to undertake the first genome-wide association study to identify genetic variants associated with sprint test performance in elite youth football players and to further validate the obtained results in additional studies. Using micro-array data (600 K-1.14 M single nucleotide polymorphisms [SNPs]) of 1,206 subjects, we identified 12 SNPs with suggestive significance after passing replication criteria. The polymorphism rs55743914 located in the PTPRK gene was found as the most significant for 5-m sprint test (p = 7.7 × 10). Seven of the discovered SNPs were also associated with sprint test performance in a cohort of 126 Polish women, and 4 were associated with power athlete status in a cohort of 399 elite Russian athletes. Six SNPs were associated with muscle fiber type in a cohort of 96 Russian subjects. We also examined genotype distributions and possible associations for 16 SNPs previously linked with sprint performance. Four SNPs (AGT rs699, HSD17B14 rs7247312, IGF2 rs680, and IL6 rs1800795) were associated with sprint test performance in this cohort. In addition, the G alleles of 2 SNPs in ADRB2 (rs1042713 & rs1042714) were significantly over-represented in these players compared with British and European controls. These results suggest that there is a genetic influence on sprint test performance in footballers, and identifies some of the genetic variants that help explain this influence.

Genome-wide identification, expression analysis and functional study of the GRAS gene family in Tartary buckwheat (Fagopyrum tataricum)

BackgroundGRAS are plant-specific transcription factors that play important roles in plant growth and development. Although the GRAS gene family has been studied in many plants, there has been little research on the GRAS genes of Tartary buckwheat (Fagopyrum tataricum), which is an important crop rich in rutin. The recently published whole genome sequence of Tartary buckwheat allows us to study the characteristics and expression patterns of the GRAS gene family in Tartary buckwheat at the genome-wide level.ResultsIn this study, 47 GRAS genes of Tartary buckwheat were identified and divided into 10 subfamilies: LISCL, HAM, DELLA, SCR, PAT1, SCL4/7, LAS, SHR, SCL3, and DLT. FtGRAS genes were unevenly distributed on 8 chromosomes, and members of the same subfamily contained similar gene structures and motif compositions. Some FtGRAS genes may have been produced by gene duplications; tandem duplication contributed more to the expansion of the GRAS gene family in Tartary buckwheat. Real-time PCR showed that the transcription levels of FtGRAS were significantly different in different tissues and fruit development stages, implying that FtGRAS might have different functions. Furthermore, an increase in fruit weight was induced by exogenous paclobutrazol, and the transcription level of the DELLA subfamily member FtGRAS22 was significantly upregulated during the whole fruit development stage. Therefore, FtGRAS22 may be a potential target for molecular breeding or genetic editing.ConclusionsCollectively, this systematic analysis lays a foundation for further study of the functional characteristics of GRAS genes and for the improvement of Tartary buckwheat crops.