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Motivation Genome-wide association studies (GWAS), particularly designed with thousands of thousands of single nucleotide polymorphisms (SNPs) (big p) genotyped on tens of thousands of subjects (small n), are encountered by a major challenge of p ≪ n. Although the integration of longitudinal information can significantly enhance a GWAS's power to comprehend the genetic architecture of complex traits and diseases, an additional challenge is generated by an autocorrelative process. We have developed several statistical models for addressing these two challenges by implementing dimension reduction methods and longitudinal data analysis. To make these models computationally accessible to applied geneticists, we wrote an R package of computer software, HiGwas, designed to analyze longitudinal GWAS data sets. Functions in the package encompass single SNP analyses, significance-level adjustment, preconditioning, and model selection for a high-dimensional set of SNPs. HiGwas provides the estimates of genetic parameters and the confidence intervals of these estimates. We demonstrate the features of HiGwas through real data analysis and vignette document in the package. Availability https//github.com/wzhy2000/higwas. Supplementary information Supplementary data are available at Bioinformatics online.Background Hypophosphatasia (HPP) is a rare inherited metabolic disorder characterized by deficient activity of the Tissue-Nonspecific Alkaline Phosphatase (TNAP) entailing impaired turnover of phosphorus metabolites. Dietary mineral intake is suspected to influence clinical symptoms of HPP, but scientific evidence is missing. Methods Cross-sectional matched-pairs study collecting comprehensive data on nutrient intake in 20 HPP patients and 20 unaffected, age- and gender-matched controls. Dietary information and clinical symptoms were documented in detail over seven consecutive days using structured diaries. Results Baseline data and type of energy-supplying nutrients were balanced between both groups. Median nutritional intake of phosphorus and calcium were significantly lower in HPP patients versus control, which is partially attributable to lower energy consumption in HPP patients. Differences regarding Ca/P ratio and uptake of Mg, Zn and Vitamin B6 were not statistically significant. Both high (≥ 1375 mg/d) and low intakes ( less then 1100 mg/d) of phosphorus were significantly associated with an increased frequency of neuropsychiatric symptoms (p = 0.02). Similarly, very high and very low intake of calcium was significantly associated with musculoskeletal (p less then 0.01), gastrointestinal (p = 0.02) and neuropsychiatric (p less then 0.001) symptoms. An increased Ca/P ratio was associated with increased tiredness/fatigue (p less then 0.01), while a decreased Ca/P was associated with gastrointestinal issues (p = 0.01). Conclusion Phosphorus and calcium intake seem reduced in HPP patients along with reduced total energy consumption. Particularly high as well as very low absolute or unbalanced phosphorus and calcium intake are associated with an increased frequency of clinical symptoms.Objective We set forth to compare ethnicities for metabolic and immunological characteristics at the clinical diagnosis of type 1 diabetes (T1D), and assess the effect of ethnicity on beta cell functional loss within three years after clinical diagnosis. Research methods and design We studied participants in TrialNet New Onset Intervention Trials (n=624, median age=14.4 years, 58% male, 8.7% Hispanics) and followed them prospectively for 3 years. Mixed meal tolerance tests (MMTT) were performed within 6 months following clinical diagnosis and repeated semiannually. Unless otherwise indicated, analyses were adjusted for age, sex, BMI Z-score, , and diabetes duration. Results At T1D clinical diagnosis, Hispanics, compared with non-Hispanic whites (NHW), had a higher frequency of diabetic ketoacidosis (DKA) (44.7% vs 25.3%, OR=2.36, p=0.01), lower fasting glucose (97 vs 109 mg/dL, p=0.02) and higher fasting C-peptide (1.23 vs 0.94 ng/mL, p=0.02) on the first MMTT, and higher frequency of ZnT8 autoantibody positivity (n=201, 94.1% vs 64%, OR=7.98, p=0.05). After exclusion of participants in experimental arms of positive clinical trials, C-peptide AUC trajectories during the first three years after clinical diagnosis were not significantly different between Hispanics and NHW after adjusting for age, sex, BMI-Z score, and DKA (n=413, p=0.14). https://www.selleckchem.com/products/FK-506-(Tacrolimus).html Conclusion Despite differences in the metabolic and immunological characteristics at clinical diagnosis of T1D between Hispanics and NHW, C-peptide trajectories did not differ significantly in the first three years following clinical diagnosis after adjustment for BMI and other confounders . These findings may inform the design of observational studies and intervention trials in T1D.During grape cultivation and wine production, the most effective way to prevent ochratoxin A (OTA) contamination of grapes and wine is the control of ochratoxigenic fungal species, and especially Aspergillus carbonarius, using the appropriate cultivation techniques. In this study, the influence of Organic (OFS) and Integrated (IFS) farming systems, on the incidence of A. carbonarius on grapes, and OTA contamination of wine, were examined. Mycological analysis of grapes, collected from Kotsifali cultivar (Vitis vinifera L.) vineyards, grown under two different farming systems (OFS and IFS), performed on two growing seasons. Moreover, at the same two growing seasons, OTA levels of representative wine samples from the wineries located in the same area, made from the same cultivar (single-varietal or co-vinificated with Mandilari) grown under the two farming systems, were determined. The results showed that the different farming systems had a significant influence on the incidence of A. carbonarius , with the IFS being the most effective regarding the control of the fungus and the prevention of OTA occurrence in wine. The knowledge could offer viticulturists a useful tool to produce safer grapes, giving the advantage to the winemakers to make low OTA levels wines.
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Motivation Genome-wide association studies (GWAS), particularly designed with thousands of thousands of single nucleotide polymorphisms (SNPs) (big p) genotyped on tens of thousands of subjects (small n), are encountered by a major challenge of p ≪ n. Although the integration of longitudinal information can significantly enhance a GWAS's power to comprehend the genetic architecture of complex traits and diseases, an additional challenge is generated by an autocorrelative process. We have developed several statistical models for addressing these two challenges by implementing dimension reduction methods and longitudinal data analysis. To make these models computationally accessible to applied geneticists, we wrote an R package of computer software, HiGwas, designed to analyze longitudinal GWAS data sets. Functions in the package encompass single SNP analyses, significance-level adjustment, preconditioning, and model selection for a high-dimensional set of SNPs. HiGwas provides the estimates of genetic parameters and the confidence intervals of these estimates. We demonstrate the features of HiGwas through real data analysis and vignette document in the package. Availability https//github.com/wzhy2000/higwas. Supplementary information Supplementary data are available at Bioinformatics online.Background Hypophosphatasia (HPP) is a rare inherited metabolic disorder characterized by deficient activity of the Tissue-Nonspecific Alkaline Phosphatase (TNAP) entailing impaired turnover of phosphorus metabolites. Dietary mineral intake is suspected to influence clinical symptoms of HPP, but scientific evidence is missing. Methods Cross-sectional matched-pairs study collecting comprehensive data on nutrient intake in 20 HPP patients and 20 unaffected, age- and gender-matched controls. Dietary information and clinical symptoms were documented in detail over seven consecutive days using structured diaries. Results Baseline data and type of energy-supplying nutrients were balanced between both groups. Median nutritional intake of phosphorus and calcium were significantly lower in HPP patients versus control, which is partially attributable to lower energy consumption in HPP patients. Differences regarding Ca/P ratio and uptake of Mg, Zn and Vitamin B6 were not statistically significant. Both high (≥ 1375 mg/d) and low intakes ( less then 1100 mg/d) of phosphorus were significantly associated with an increased frequency of neuropsychiatric symptoms (p = 0.02). Similarly, very high and very low intake of calcium was significantly associated with musculoskeletal (p less then 0.01), gastrointestinal (p = 0.02) and neuropsychiatric (p less then 0.001) symptoms. An increased Ca/P ratio was associated with increased tiredness/fatigue (p less then 0.01), while a decreased Ca/P was associated with gastrointestinal issues (p = 0.01). Conclusion Phosphorus and calcium intake seem reduced in HPP patients along with reduced total energy consumption. Particularly high as well as very low absolute or unbalanced phosphorus and calcium intake are associated with an increased frequency of clinical symptoms.Objective We set forth to compare ethnicities for metabolic and immunological characteristics at the clinical diagnosis of type 1 diabetes (T1D), and assess the effect of ethnicity on beta cell functional loss within three years after clinical diagnosis. Research methods and design We studied participants in TrialNet New Onset Intervention Trials (n=624, median age=14.4 years, 58% male, 8.7% Hispanics) and followed them prospectively for 3 years. Mixed meal tolerance tests (MMTT) were performed within 6 months following clinical diagnosis and repeated semiannually. Unless otherwise indicated, analyses were adjusted for age, sex, BMI Z-score, , and diabetes duration. Results At T1D clinical diagnosis, Hispanics, compared with non-Hispanic whites (NHW), had a higher frequency of diabetic ketoacidosis (DKA) (44.7% vs 25.3%, OR=2.36, p=0.01), lower fasting glucose (97 vs 109 mg/dL, p=0.02) and higher fasting C-peptide (1.23 vs 0.94 ng/mL, p=0.02) on the first MMTT, and higher frequency of ZnT8 autoantibody positivity (n=201, 94.1% vs 64%, OR=7.98, p=0.05). After exclusion of participants in experimental arms of positive clinical trials, C-peptide AUC trajectories during the first three years after clinical diagnosis were not significantly different between Hispanics and NHW after adjusting for age, sex, BMI-Z score, and DKA (n=413, p=0.14). https://www.selleckchem.com/products/FK-506-(Tacrolimus).html Conclusion Despite differences in the metabolic and immunological characteristics at clinical diagnosis of T1D between Hispanics and NHW, C-peptide trajectories did not differ significantly in the first three years following clinical diagnosis after adjustment for BMI and other confounders . These findings may inform the design of observational studies and intervention trials in T1D.During grape cultivation and wine production, the most effective way to prevent ochratoxin A (OTA) contamination of grapes and wine is the control of ochratoxigenic fungal species, and especially Aspergillus carbonarius, using the appropriate cultivation techniques. In this study, the influence of Organic (OFS) and Integrated (IFS) farming systems, on the incidence of A. carbonarius on grapes, and OTA contamination of wine, were examined. Mycological analysis of grapes, collected from Kotsifali cultivar (Vitis vinifera L.) vineyards, grown under two different farming systems (OFS and IFS), performed on two growing seasons. Moreover, at the same two growing seasons, OTA levels of representative wine samples from the wineries located in the same area, made from the same cultivar (single-varietal or co-vinificated with Mandilari) grown under the two farming systems, were determined. The results showed that the different farming systems had a significant influence on the incidence of A. carbonarius , with the IFS being the most effective regarding the control of the fungus and the prevention of OTA occurrence in wine. The knowledge could offer viticulturists a useful tool to produce safer grapes, giving the advantage to the winemakers to make low OTA levels wines.
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