Biology subjects

Haas, M.

Publications and source records attributed to Haas, M..

5 recordsLinked to original sources

bioRxiv2018

Genetic association of photoplethysmography-derived arterial stiffness index with blood pressure and coronary artery disease

BackgroundArterial stiffness index (ASI) is independently associated with blood pressure and coronary artery disease (CAD) in epidemiologic studies. However, it is unknown whether these associations represent causal relationships.\n\nObjectivesHere, we assess whether genetic predisposition to increased ASI is associated with elevated blood pressure and CAD risk.\n\nMethodsGenome-wide association analysis (GWAS) of finger photoplethysmography-derived ASI was performed in 131,686 participants from the UK Biobank. Across UK Biobank participants not in the ASI GWAS, a 6-variant ASI polygenic risk score was calculated. The ASI polygenic score was associated with systolic and diastolic blood pressures (SBP, DBP, N=208,897), and with incident CAD over 10 years follow-up (N=223,061; 7,534 cases). The lack of CAD association observed was replicated among 184,305 participants (60,810 cases) from the Coronary Artery Disease Genetics Consortium (CARDIOGRAMplusC4D).\n\nResultsWe replicated prior reports of the epidemiologic association of ASI with SBP (Beta 0.55mmHg, [95% CI, 0.45-0.65], P=5.77x10-24), DBP (Beta 1.05mmHg, [95% CI, 0.99-1.11], P=7.27x10-272), and incident CAD (HR 1.08 [95% CI, 1.04-1.11], P=1.5x10-6) in multivariable models. While each SD increase in genetic predisposition to elevated ASI was highly associated with SBP (Beta 4.63 mmHg [95% CI, 2.1-7.2]; P=3.37x10-4), and DBP (Beta 2.61 mmHg [95% CI, 1.2-4.0]; P=2.85x10-4), no association was observed with incident CAD in UK Biobank (HR 1.12 [95% CI, 0.55-2.3]; P=0.75), or with prevalent CAD in CARDIOGRAMplusC4D (OR 0.56 [95% CI, 0.26-1.24]; P=0.15).\n\nConclusionsA genetic predisposition to higher ASI was associated with elevated blood pressure but not with increased risk of developing CAD.\n\nCondensed AbstractArterial stiffness index (ASI) is proposed by some as a surrogate of blood pressure and coronary artery disease (CAD) risk based on epidemiologic analyses. We tested whether genetic predisposition to increased ASI is associated with elevated blood pressure and CAD risk to assess whether these represent causal relationships. We find that a genetic predisposition to higher ASI is associated with elevated systolic (Beta 4.63 mmHg [95% CI, 2.1-7.2]) and diastolic blood pressures (Beta 2.61 mmHg [95% CI, 1.2-4.0]) in the UK Biobank, but not associated with incident CAD in the UK Biobank (P=0.75) or with prevalent CAD in CARDIOGRAMplusC4D (P=0.15). These data support a causal relationship of ASI with blood pressure but do not support the notion that ASI is a suitable surrogate for CAD risk.

bioinformatics↗

bioRxiv2018

RNA-seq reveals few differences in resistant and susceptible responses of barley to infection by the spot blotch pathogen Bipolaris sorokiniana

Spot blotch, caused by Bipolaris sorokiniana (Sacc.) Shoem., is an economically important disease affecting barley (Hordeum vulgare L.). The disease has largely been controlled in the Upper Midwest region of the USA through a suite of quantitative trait loci (QTL) termed the Midwest Six-rowed Durable Resistance Haplotype (MSDRH). These QTL have been bred into all six-rowed Midwest barley cultivars, including the widely used cultivar Morex. We identified a gamma ray- induced Morex mutant (MUT) that exhibits spot blotch susceptibility at the seedling stage. This mutant also spontaneously develops extremely large necrotic lesions in the absence of the pathogen at the adult plant stage. Spot blotch susceptibility at the seedling stage and necrotic lesion formation at the adult plant stage are highly correlated. To start dissecting the molecular responses underlying the observed symptoms at the seedling stage, we conducted a time course RNA-seq experiment comparing the wild type (WT) and the mutant (MUT) Morex at 12, 24 and 36 h after B. sorokiniana inoculation. Mock-inoculated controls were also included. A total of 10,772 and 11,530 genes were differentially expressed between treatments for WT and MUT genotypes, respectively, while 277 and 195 genes were differentially expressed between fungal and mock-inoculated genotypes, respectively. The transcript expression profiles of WT and MUT Morex samples were similar for most treatments. Two genes whose expression was putatively knocked out in the MUT were identified: HORVU3Hr1G019920 (glycine-rich protein) and HORVU5Hr1G120850 (Long- chain-fatty-acid--CoA ligase 1). The latter appears to be genetically intact, but not expressed. Collectively, these data suggest that MUT susceptibility to B. sorokiniana is a result of minor, rather than major, differences in the defense responses.

genetics↗

bioRxiv2018

Genetic Diversity Study of Fusarium culmorum: Causal agent of wheat crown rot in Iraq

Fusarium crown rot (FCR), caused by Fusarium culmorum (Wm.G.Sm) Sacc., is an important disease of wheat both in Iraq and other regions of wheat production worldwide. Changes in environmental conditions and cultural practices such as crop rotation generate stress on pathogen populations leading to the evolution of new strains that can tolerate more stressful environments. This study aims to investigate the genetic diversity among isolates of F. culmorum in Iraq. Twenty-nine samples were collected from different regions of wheat cultivation in Iraq to investigate the pathogenicity and genetic diversity of F. culmorum using the REP-PCR technique. Among the twenty-nine isolates of F. culmorum examined for pathogenicity, 96% were pathogenic to wheat at the seedling stage. The most aggressive isolate, from Baghdad, was IF 0021 at 0.890 on the FCR severity index. Three primer sets were used to assess the genotypic diversity via REP, ERIC and BOX elements. The amplicon sizes ranged from 200-800 bp for BOX-ERIC2, 110-1100 bp for ERIC-ERIC2 and 200-1300 bp for REP. In total, 410 markers were polymorphic, including 106 for BOX, 175 for ERIC and 129 for the REP. Genetic similarity was calculated by comparing markers according to minimum variance (Squared Euclidean). Clustering analysis generated two major groups, group 1 with two subgroup 1a and 1b with 5 and 12 isolates respectively, and group 2 with two subgroups 2a and 2b with 3 and 9 isolates respectively. This is the first study in this field that has been reported in Iraq.

microbiology↗

bioRxiv2017

Genome-wide polygenic score to identify a monogenic risk-equivalent for coronary disease

Identification of individuals at increased genetic risk for a complex disorder such as coronary disease can facilitate treatments or enhanced screening strategies. A rare monogenic mutation associated with increased cholesterol is present in ~1:250 carriers and confers an up to 4-fold increase in coronary risk when compared with non-carriers. Although individual common polymorphisms have modest predictive capacity, their cumulative impact can be aggregated into a polygenic score. Here, we develop a new, genome-wide polygenic score that aggregates information from 6.6 million common polymorphisms and show that this score can similarly identify individuals with a 4-fold increased risk for coronary disease. In >400,000 participants from UK Biobank, the score conforms to a normal distribution and those in the top 2.5% of the distribution are at 4-fold increased risk compared to the remaining 97.5%. Similar patterns are observed with genome-wide polygenic scores for two additional diseases - breast cancer and severe obesity.\n\nOne Sentence SummaryA genome-wide polygenic score identifies 2.5% of the population born with a 4-fold increased risk for coronary artery disease.

genomics↗

bioRxiv2017

Quantifying 35 transcripts in a single tube: Model-based calibration of the GeXP RT-PCR assay

Quantitative analysis of differential gene expression is of central importance in molecular life sciences. The Gene eXpression Profiling technology (GeXP) relies on multiplex RT-PCR and subsequent capillary electrophoretic separation of the amplification products and allows to quantify the transcripts of up to approximately 35 genes with a single reaction and one dye. Here, we provide a kinetic model of primer binding and PCR product formation as the rational basis for taking and evaluating calibration curves. With the help of a purposeful designed data processing workflow supported by easy-to-use Perl scripts for calibration, data evaluation, and quality control, the calibration procedure and the model predictions were confirmed and the robustness and linearity of transcript quantification demonstrated for differentiating Physarum polycephalum plasmodial cells. We conclude that GeXP analysis is a robust, sensitive, and useful method when the transcripts of tens to few hundred genes are to be precisely quantified in a high number of samples.

systems biology↗