Genome-Wide Interaction Analysis with DASH Diet Score Identified Novel Loci for Systolic Blood Pressure

OBJECTIVE: We examined interactions between genotype and a Dietary Approaches to Stop Hypertension (DASH) diet score in relation to systolic blood pressure (SBP).METHODS: We analyzed up to 9,420,585 biallelic imputed single nucleotide polymorphisms (SNPs) in up to 127,282 individuals of six population groups (91% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (CHARGE; n=35,660) and UK Biobank (n=91,622) and performed European population-specific and cross-population meta-analyses.RESULTS: We identified three loci in European-specific analyses and an additional four loci in cross-population analyses at P for interaction &lt; 5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency = 0.03) and the DASH diet score (P for interaction = 4e-8; P for heterogeneity = 0.35) in European population, where the interaction effect size was 0.42±0.09 mm Hg (P for interaction = 9.4e-7) and 0.20±0.06 mm Hg (P for interaction = 0.001) in CHARGE and the UK Biobank, respectively. The 1 Mb region surrounding rs117878928 was enriched with cis-expression quantitative trait loci (eQTL) variants (P = 4e-273) and cis-DNA methylation quantitative trait loci (mQTL) variants (P = 1e-300). While the closest gene for rs117878928 is MTHFS, the highest narrow sense heritability accounted by SNPs potentially interacting with the DASH diet score in this locus was for gene ST20 at 15q25.1. CONCLUSION: We demonstrated gene-DASH diet score interaction effects on SBP in several loci. Studies with larger diverse populations are needed to validate our findings.</p

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

The Perfect Garden

With hands-on work in the Chris Robb Garden, we researched what was the best method for preparing a proper organic garden. After the garden was created in 2012, Dr. Brunell and his students are still researching the best method for creating a productive, pesticide-free, all-natural garden that produces a variety of delicious, high-yield produce in addition to maintaining the soil’s health. To research the best method to maintain the garden, we first prepared the beds for plants. Cover crops, which were planted to naturally restore nutrients and nitrogen in the soil, were removed. Then, we turned the soil to aerate it and mixed it with chicken manure and an organic soil amender called Black Gold to add more nutrients back into the soil. After starting different plants from seeds, we transplanted these seedlings to the garden and planted them into six inch deep holes about four or eight inches apart. Drip tape was used as a watering system and covers were used in the winter to protect the plants from harsh weather. This semester we harvested a variety of vegetables in great abundance, some of which included kale, Asian greens, broccoli, lettuce, collard, cabbage, kohlrabi, and peas. To waste nothing in the garden, compost piles were made using plant waste that will break down and be used as new soil and nutrients for the beds. Our harvests have gone to the school’s Farmer’s Market and dining service, Bon Appetit, every Wednesday for students, faculty, and others to buy and enjoy

The Perfect Garden

With hands-on work in the Chris Robb Garden, we researched what was the best method for preparing a proper organic garden. After the garden was created in 2012, Dr. Brunell and his students are still researching the best method for creating a productive, pesticide-free, all-natural garden that produces a variety of delicious, high-yield produce in addition to maintaining the soil’s health. To research the best method to maintain the garden, we first prepared the beds for plants. Cover crops, which were planted to naturally restore nutrients and nitrogen in the soil, were removed. Then, we turned the soil to aerate it and mixed it with chicken manure and an organic soil amender called Black Gold to add more nutrients back into the soil. After starting different plants from seeds, we transplanted these seedlings to the garden and planted them into six inch deep holes about four or eight inches apart. Drip tape was used as a watering system and covers were used in the winter to protect the plants from harsh weather. This semester we harvested a variety of vegetables in great abundance, some of which included kale, Asian greens, broccoli, lettuce, collard, cabbage, kohlrabi, and peas. To waste nothing in the garden, compost piles were made using plant waste that will break down and be used as new soil and nutrients for the beds. Our harvests have gone to the school’s Farmer’s Market and dining service, Bon Appetit, every Wednesday for students, faculty, and others to buy and enjoy

Exploring the Valley of Savings: Minimizing Part D Costs and Optimizing Drug Therapy Outcomes in Medicare Beneficiaries With Developmental Disability

Nonelderly disabled Medicare beneficiaries have a higher prevalence of chronic conditions, higher utilization of prescription medications, and increased demand for clinical services when compared to beneficiaries 65 years of age and older who are not disabled. Out-of-pocket costs and medication-related problems are major barriers to medication compliance and achievement of therapeutic goals. A school of pharmacy partnered with a nonprofit organization that provides care to individuals with developmental disabilities. The present study highlights outcomes resulting from (a) providing Medicare Part D plan optimization services to lower prescription drug costs and (b) Medication Therapy Management services to evaluate safe and effective medication use in this beneficiary population. Provided interventions were shown to reduce overall medication costs and identify significant medication-related problems

Genome-Wide Interaction Analysis with DASH Diet Score Identified Novel Loci for Systolic Blood Pressure

OBJECTIVE: We examined interactions between genotype and a Dietary Approaches to Stop Hypertension (DASH) diet score in relation to systolic blood pressure (SBP).METHODS: We analyzed up to 9,420,585 biallelic imputed single nucleotide polymorphisms (SNPs) in up to 127,282 individuals of six population groups (91% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (CHARGE; n=35,660) and UK Biobank (n=91,622) and performed European population-specific and cross-population meta-analyses.RESULTS: We identified three loci in European-specific analyses and an additional four loci in cross-population analyses at P for interaction &lt; 5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency = 0.03) and the DASH diet score (P for interaction = 4e-8; P for heterogeneity = 0.35) in European population, where the interaction effect size was 0.42±0.09 mm Hg (P for interaction = 9.4e-7) and 0.20±0.06 mm Hg (P for interaction = 0.001) in CHARGE and the UK Biobank, respectively. The 1 Mb region surrounding rs117878928 was enriched with cis-expression quantitative trait loci (eQTL) variants (P = 4e-273) and cis-DNA methylation quantitative trait loci (mQTL) variants (P = 1e-300). While the closest gene for rs117878928 is MTHFS, the highest narrow sense heritability accounted by SNPs potentially interacting with the DASH diet score in this locus was for gene ST20 at 15q25.1. CONCLUSION: We demonstrated gene-DASH diet score interaction effects on SBP in several loci. Studies with larger diverse populations are needed to validate our findings.</p

Associations of autozygosity with a broad range of human phenotypes

Abstract: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding

Genome-Wide Interaction Analysis with DASH Diet Score Identified Novel Loci for Systolic Blood Pressure

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet score lowers blood pressure (BP). We examined interactions between genotype and the DASH diet score in relation to systolic BP. METHODS: We analyzed up to 9420585 single nucleotide polymorphisms in up to 127282 individuals of 6 population groups (91% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (n=35660) and UK Biobank (n=91622) and performed European population-specific and cross-population meta-analyses. RESULTS: We identified 3 loci in European-specific analyses and an additional 4 loci in cross-population analyses at Pinteraction&lt;5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency, 0.03) and the DASH diet score (Pinteraction=4e-8; P for heterogeneity, 0.35) in European population, where the interaction effect size was 0.42±0.09 mmHg (Pinteraction=9.4e-7) and 0.20±0.06 mmHg (Pinteraction=0.001) in Cohorts for Heart and Aging Research in Genomic Epidemiology and the UK Biobank, respectively. The 1 Mb region surrounding rs117878928 was enriched with cis-expression quantitative trait loci (eQTL) variants (P=4e-273) and cis-DNA methylation quantitative trait loci variants (P=1e-300). Although the closest gene for rs117878928 is MTHFS, the highest narrow sense heritability accounted by single nucleotide polymorphisms potentially interacting with the DASH diet score in this locus was for gene ST20 at 15q25.1. CONCLUSIONS: We demonstrated gene-DASH diet score interaction effects on systolic BP in several loci. Studies with larger diverse populations are needed to validate our findings.</p