Association between systemic lupus erythematosus and inflammatory bowel disease in European and East Asian populations: a two-sample Mendelian randomization study

BackgroundPrevious studies have shown a coexistence phenomenon between systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), but the causal relationship between them is still unclear. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis using publicly available summary statistics data to evaluate whether there was a causal relationship between the two diseases.MethodsSummary statistics for SLE and IBD were downloaded from the Open Genome-Wide Association Study and the International Inflammatory Bowel Disease Genetics Consortium. European and East Asian populations were included in this MR work. We adopted a series of methods to select instrumental variables that are closely related to SLE and IBD. To make the conclusion more reliable, we applied a variety of different analysis methods, among which the inverse variance–weighted (IVW) method was the main method. In addition, heterogeneity, pleiotropy, and sensitivity were assessed to make the conclusions more convincing.ResultsIn the European population, a negative causal relationship was observed between SLE and overall IBD (OR = 0.94; 95% CI = 0.90, 0.98; P < 0.004) and ulcerative colitis (UC) (OR = 0.93; 95% CI = 0.88, 0.98; P = 0.006). After removing outliers with Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), the results remained consistent with IVW. However, there was no causal relationship between SLE and Crohn’s disease. In the East Asian population, no causal relationship was found between SLE and IBD.ConclusionOur results found that genetic susceptibility to SLE was associated with lower overall IBD risk and UC risk in European populations. In contrast, no association between SLE and IBD was found in East Asian populations. This work might enrich the previous research results, and it may provide some references for research in the future

Fine Mapping of the Bsr1 Barley Stripe Mosaic Virus Resistance Gene in the Model Grass Brachypodium distachyon

The ND18 strain of Barley stripe mosaic virus (BSMV) infects several lines of Brachypodium distachyon, a recently developed model system for genomics research in cereals. Among the inbred lines tested, Bd3-1 is highly resistant at 20 to 25°C, whereas Bd21 is susceptible and infection results in an intense mosaic phenotype accompanied by high levels of replicating virus. We generated an F6∶7 recombinant inbred line (RIL) population from a cross between Bd3-1 and Bd21 and used the RILs, and an F2 population of a second Bd21 × Bd3-1 cross to evaluate the inheritance of resistance. The results indicate that resistance segregates as expected for a single dominant gene, which we have designated Barley stripe mosaic virus resistance 1 (Bsr1). We constructed a genetic linkage map of the RIL population using SNP markers to map this gene to within 705 Kb of the distal end of the top of chromosome 3. Additional CAPS and Indel markers were used to fine map Bsr1 to a 23 Kb interval containing five putative genes. Our study demonstrates the power of using RILs to rapidly map the genetic determinants of BSMV resistance in Brachypodium. Moreover, the RILs and their associated genetic map, when combined with the complete genomic sequence of Brachypodium, provide new resources for genetic analyses of many other traits

Establishment of a Nomogram for Predicting Early Death in Viral Myocarditis

Objective. This research aimed to establish a nomogram for predicting early death in viral myocarditis (VMC) patients. Method. A total of 362 consecutive VMC patients in Fujian Medical University Affiliated First Quanzhou Hospital between January 1, 2009, and December 31, 2019, were included. A least absolute shrinkage and selection operator (LASSO) regression model was used to detect the risk factors that most consistently and correctly predicted early death in VMC. The performance of the nomogram was assessed by calibration, discrimination, and clinical utility. Result. 9 factors were screened by LASSO regression analysis for predicting the early death of VMC. Combined with the actual clinical situation, the heart failure (HF) (OR: 2.13, 95% CI: 2.76–5.95), electrocardiogram (ECG) (OR: 6.11, 95% CI: 1.05–8.66), pneumonia (OR: 3.62, 95% CI: 1.43–9.85), brain natriuretic peptide (BNP) (OR: 4.66, 95% CI: 3.07–24.06), and lactate dehydrogenase (LDH) (OR: 1.90, 95% CI: 0.19–9.39) were finally used to construct the nomogram. The nomogram’s C-index was 0.908 in the training cohort and 0.924 in the validation cohort. And the area under the receiver operating characteristic curve of the nomogram was 0.91 in the training cohort and 0.924 in the validating cohort. Decision curve analysis (DCA) also showed that the nomogram was clinically useful. Conclusion. This nomogram achieved an good prediction of the risk of early death in VMC patients

Fine mapping of the Bsr1 barley stripe mosaic virus resistance gene in the model grass Brachypodium distachyon.

The ND18 strain of Barley stripe mosaic virus (BSMV) infects several lines of Brachypodium distachyon, a recently developed model system for genomics research in cereals. Among the inbred lines tested, Bd3-1 is highly resistant at 20 to 25 °C, whereas Bd21 is susceptible and infection results in an intense mosaic phenotype accompanied by high levels of replicating virus. We generated an F(6:7) recombinant inbred line (RIL) population from a cross between Bd3-1 and Bd21 and used the RILs, and an F(2) population of a second Bd21 × Bd3-1 cross to evaluate the inheritance of resistance. The results indicate that resistance segregates as expected for a single dominant gene, which we have designated Barley stripe mosaic virus resistance 1 (Bsr1). We constructed a genetic linkage map of the RIL population using SNP markers to map this gene to within 705 Kb of the distal end of the top of chromosome 3. Additional CAPS and Indel markers were used to fine map Bsr1 to a 23 Kb interval containing five putative genes. Our study demonstrates the power of using RILs to rapidly map the genetic determinants of BSMV resistance in Brachypodium. Moreover, the RILs and their associated genetic map, when combined with the complete genomic sequence of Brachypodium, provide new resources for genetic analyses of many other traits

A rare gain of function mutation in a wheat tandem kinase confers resistance to powdery mildew.

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most destructive diseases that pose a great threat to wheat production. Wheat landraces represent a rich source of powdery mildew resistance. Here, we report the map-based cloning of powdery mildew resistance gene Pm24 from Chinese wheat landrace Hulutou. It encodes a tandem kinase protein (TKP) with putative kinase-pseudokinase domains, designated WHEAT TANDEM KINASE 3 (WTK3). The resistance function of Pm24 was validated by transgenic assay, independent mutants, and allelic association analyses. Haplotype analysis revealed that a rare 6-bp natural deletion of lysine-glycine codons, endemic to wheat landraces of Shaanxi Province, China, in the kinase I domain (Kin I) of WTK3 is critical for the resistance function. Transgenic assay of WTK3 chimeric variants revealed that only the specific two amino acid deletion, rather than any of the single or more amino acid deletions, in the Kin I of WTK3 is responsible for gaining the resistance function of WTK3 against the Bgt fungus

Segregation ratios of Bd21 × Bd3-1 F₂ and Bd3-1 × Bd21F_6∶7 RIL populations for BSMV ND18 resistance.

<p>Segregation ratios of Bd21 × Bd3-1 F₂ and Bd3-1 × Bd21F_6∶7 RIL populations for BSMV ND18 resistance.</p

Comparison of SNP-based genetic linkage maps of Bd3-1 × Bd21 F₂ and F_6∶7 RIL populations.

<p>Note: Chr 1 includes small groups A, B, D; Chr 2 includes small group C.</p

Geographic and genotypic distributions of the phenotype elicited during BSMV ND18 infection of diverse Brachypodium lines.

<p><b>A</b>) Infection phenotype of 44 Brachypodium lines from 11 locations in Turkey. Red dots represent the locations of the 33 susceptible lines; Green dots show the distribution of the 11 resistant lines. <b>B</b>) Plot of the phenotypic responses of the Brachypodium lines on a previously created neighbor joining tree based 44 SSR markers (Vogel et. al. 2009). Red ovals represent susceptible lines and green ovals show resistant lines.</p

Disease responses of Brachypodium lines Bd3-1, Bd21 and Bd21-3 to infection with BSMV ND18.

<p>(<b>A–C</b>) Uninfected Bd3-1 and inoculated Bd-3-1, Bd21 and Bd21-3 at 12 dpi. (A) Uninfected Bd3-1 plants remained green and continued to grow rapidly, as was typical of uninfected Bd21 and Bd21-3 plants. Nd18 inoculated Bd3-1 plants failed to develop symptoms and had the same general appearance as their uninoculated counterparts. In contrast, Bd21 and Bd21-3 inoculated plants developed visible mosaic symptoms on emerging leaves by 7 days post inoculation (dpi) and the symptoms remain visible until at least 20 dpi. (<b>B</b>) Western blots to determine the presence of the 22 KD BSMV coat protein in leaf extracts from the first emerging leaf of uninoculated and inoculated plants at 6 dpi. (<b>C</b>) RT-PCR analyses of leaf extracts taken at 21 dpi from the lines shown in the top panel. A forward primer complementary to the 3′ end of BSMV RNAs and a reverse primer of the same polarity as the γb gene were designed to produce an ∼800 nt product. (<b>D–E</b>) Chronic disease symptoms on Brachypodium lines inoculated with BSMV ND18. (<b>D</b>) Bd3-1 and Bd21 at 25 dpi. Note stunting of Bd21 compared to Bd3-1. (<b>E</b>) Healthy Bd3-1 and Bd 3-1 and Bd21 at 55 dpi. <b>Note:</b> Uninoculated plants and inoculated Bd3-1 plants have a similar growth characteristics and seed population, but Bd21 plants are stunted and fail to flower or set seeds.</p