Genome-wide association study uncovers new genetic loci and candidate genes underlying seed chilling-germination in maize

As one of the major crops, maize (Zea mays L.) is mainly distributed in tropical and temperate regions. However, with the changes of the environments, chilling stress has become a significantly abiotic stress affecting seed germination and thus the reproductive and biomass accumulation of maize. Herein, we investigated five seed germination-related phenotypes among 300 inbred lines under low-temperature condition (10 °C). By combining 43,943 single nucleotide polymorphisms (SNPs), a total of 15 significant (P < 2.03 ×  10-6) SNPs were identified to correlate with seed germination under cold stress based on the FarmCPU model in GWAS, among which three loci were repeatedly associated with multiple traits. Ten gene models were closely linked to these three variations, among which Zm00001d010454, Zm00001d010458, Zm00001d010459, and Zm00001d050021 were further verified by candidate gene association study and expression pattern analysis. Importantly, these candidate genes were previously reported to involve plant tolerance to chilling stress and other abiotic stress. Our findings contribute to the understanding of the genetic and molecular mechanisms underlying chilling germination in maize

Genetic Polymorphisms in Enzymes Involved in One-Carbon Metabolism and Anti-epileptic Drug Monotherapy on Homocysteine Metabolism in Patients With Epilepsy

Aims: To investigate the effects of single nucleotide polymorphisms (SNPs) in genes of one-carbon metabolism (OCM) related enzymes and anti-epileptic drug (AED) monotherapy on homocysteine (Hcy) metabolism in patients with epilepsy, and to further explore specific SNPs that may increase patients' susceptibility to the effects of AEDs on the Hcy imbalance.Method: This case-control study analyzed 279 patients with epilepsy, including patients receiving monotherapy with valproate (VPA) (n = 53), oxcarbazepine (OXC) (n = 71), lamotrigine (LTG) (n = 55), or levetiracetam (LEV) (n = 35) and patients who had not taken any AEDs (controls, n = 65) for at least 6 months. Serum levels of vitamin B12 (vit B12), folate (FA) and Hcy were measured, and 23 SNPs in 13 genes of OCM-related enzymes were genotyped in all patients.Results: Methylenetetrahydrofolate reductase (MTHFR) rs1801133 was associated with elevated serum Hcy levels in patients with epilepsy (P &lt; 0.001), and patients presenting the TT genotype exhibited higher serum Hcy levels than patients with the CC (P &lt; 0.001) or CT (P &lt; 0.001) genotype. A subsequent multiple linear regression analysis showed that AED monotherapy with VPA (vs. control: P = 0.023) or OXC (vs. control: P = 0.041), and genotypes of MTHFR rs1801133 TT (vs. CC: P &lt; 0.001; vs. CT: P &lt; 0.001), transcobalamin 2 (TCN2) rs1801198 CC (vs. GC: P = 0.039) and folate receptor 1 (FOLR1) rs2071010 AA (vs. GA: P = 0.031) were independent risk factors for higher Hcy levels. In the subgroup analysis of patients taking OXC, we found that patients with genotypes of MTHFR rs1801133 TT (vs. CC: P = 0.001; vs. CT: P &lt; 0.001) and TCN2 rs1801198 CC (vs. GC: P = 0.021; vs. GG: P = 0.018) exhibited higher serum Hcy levels.Conclusions: VPA, OXC, and genotypes of MTHFR rs1801133 TT, TCN2 rs1801198 CC, and FOLR1 rs2071010 AA are all independent risk factors for elevated Hcy levels in patients with epilepsy. Moreover, genotypes of MTHFR rs1801133 TT and TCN2 rs1801198 CC may increase patients' susceptibility to the effect of OXC on disrupting Hcy homeostasis

SINGLE-RUN SIMULATION OPTIMIZATION THROUGH TIME DILATION AND OPTIMAL COMPUTING BUDGET ALLOCATION AND SOME APPLICATIONS

Ph.DDOCTOR OF PHILOSOPH

Lipids, lipid-modifying drug target genes and migraine: a Mendelian randomization study

Abstract Introduction Migraine, a prevalent headache disorder with unclear mechanisms and limited treatments, may be influenced by dyslipidemia and genetic factors. Statins and emerging lipid-modifying agents show potential but lack evidence for migraine management. Mendelian Randomization analysis offers insights into causal relationships and therapeutic targets. This study aims to explore genetically predicted lipid traits, drug targets, and their association with migraine risk. Method We conducted Mendelian randomization (MR) analyses utilizing genetic variants associated with lipid traits and variants in genes encoding the protein targets of various classes of lipid-lowering drugs. The specific drug classes investigated included HMGCR, PCSK9, NPC1L1, ABCG5/ABCG8, LDLR, LPL, ANGPTL3, APOB, CETP, and APOC3. To determine the effects on migraine risk, we meta-analyzed MR estimates for regional variants using data from two large sample sets. The genetic variants were weighted based on their associations with specific lipid traits, such as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Apolipoprotein A1, and Apolipoprotein B. To obtain association weights, we utilized data from lipid genetics consortia. For lipid-modifying drug targets that exhibited suggestive significance, we further employed expression quantitative trait locus (eQTL) data. Additionally, we performed colocalization analysis to assess genetic confounding. Result The use of genetic proxies for HMGCR inhibition demonstrated a significant association with a decreased risk of migraine in the FinnGen dataset (OR = 0.64, 95% CI: 0.46–0.88, p = 0.0006) and a nearly significant association in the Choquet dataset (OR = 0.78, 95% CI: 0.60–1.01, p = 0.06). When pooling the estimates, the overall effect size showed a reduced risk of migraine (OR = 0.73, 95% CI: 0.60–0.89, p = 0.0016). Similarly, genetic mimicry of LPL enhancement was associated with a lower risk of migraine in the FinnGen dataset (OR = 0.82, 95% CI: 0.69–0.96, p = 0.01) and the Choquet dataset (OR = 0.91, 95% CI: 0.83–0.99, p = 0.03). Pooling the estimates showed a consistent effect size (OR = 0.89, 95% CI: 0.83–0.96, p = 0.002). Sensitivity analyses yielded no statistically significant evidence of bias arising from pleiotropy or genetic confounding. Conclusion In the study, it was observed that among the 10 lipid-lowering drug targets investigated, LPL and HMGCR showed significant associations with migraine risk. These findings indicate that LPL and HMGCR have the potential to serve as candidate drug targets for the treatment or prevention of migraines

A randomized controlled trial to evaluate the impact of a geo-specific poster compared to a general poster for effecting change in perceived threat and intention to avoid drowning \u27hotspots\u27 among children of migrant workers: evidence from Ningbo, China

Background Drowning among children of migrant workers is a major, though neglected public health issue in China. Methods A randomised controlled trial was used to examine the potential impact of viewing a preventive health poster with/without geo-located drowning events on perceptions of drowning risk among Chinese migrant children. A total of 752 children from three schools in Jiangbei district were selected by multi-stage sampling and randomly assigned to the intervention (n = 380) or control (n = 372). Multilevel models were used to analyse changes in responses to the following questions after viewing the assigned poster for 10 min: (1) “Do you believe that drowning is a serious health problem in Ningbo city?”; (2) “Do you believe that there are lots of drowning-risk waters around you?”; (3) “Do you believe that the likelihood of your accessing a drowning-risk water is great?”; and (4) “Would you intend to avoid accessing to those drowning-risk waters when being exposed?” Results At baseline there were no significant differences between the intervention and control groups in perceptions of drowning risk or covariates. Following the intervention, participants that viewed the geo-specific poster were more likely to respond more favourably to the first three questions (p \u3c 0.001) than those who viewed the standard poster. However, there was no substantive difference between the geo-specific or standard poster in terms of changing intentions to avoid drowning hotspots (p = 0.214). Conclusions Use of ‘geo-located’ information added value to the effectiveness of a drowning prevention poster for enhancing awareness of drowning hotspots among children of migrant workers

TD-OCBA: Optimal Computing Budget Allocation and Time Dilation for Simulation Optimization of Manufacturing Systems

10.1080/24725854.2018.1488305IISE Transactions513219-23

Additional file 13 of Lipids, lipid-modifying drug target genes and migraine: a Mendelian randomization study

Additional file 13: Figure S13. Scatter plot of the association between LDL and migraine using SNPs within or near the PCSK9 locus in (a) Finngen dataset (b) Choquet dataset

Correction: Transcriptome analysis of tomato (Solanum lycopersicum L.) shoots reveals a crosstalk between auxin and strigolactone.

[This corrects the article DOI: 10.1371/journal.pone.0201124.]

Additional file 9 of Lipids, lipid-modifying drug target genes and migraine: a Mendelian randomization study

Additional file 9: Figure S9. Scatter plot of the association between LDL and migraine using SNPs within or near the HMGCR locus in (a) Finngen dataset (b) Choquet dataset

Additional file 16 of Lipids, lipid-modifying drug target genes and migraine: a Mendelian randomization study

Additional file 16: Figure S16. Scatter plot of the association between TG and migraine using SNPs within or near the APOC3 locus in (a) Finngen dataset (b) Choquet dataset