scholarly journals Methylation-wide association analysis reveals AIM2, DGUOK, GNAI3, and ST14 genes as potential contributors to the Alzheimer’s disease pathogenesis

2018 ◽  
Author(s):  
Alireza Nazarian ◽  
Anatoliy I. Yashin ◽  
Alexander M. Kulminski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Cognitive Abilities ◽  
Large Scale ◽  
Neurodegenerative Disorder ◽  
The United States ◽  
Association Analyses ◽  
Trait Loci

ABSTRACTIntroduction: Alzheimer’s disease (AD) is a progressive complex neurodegenerative disorder with devastating impact on cognitive abilities. It is among the top 10 leading causes of death in the United States with no curative medications. Exploring genetic and non-genetic contributors to AD development is, therefore, of great importance.Methods: We investigated the AD-associated epigenetic changes by combing results from publicly available genome-wide association analyses and a large-scale methylation quantitative trait loci study.Results: Probes mapped to 133 genes were associated with AD with < 2.50E-06. Of these, four genes (i.e., GNAI3, AIM2, DGUOK and ST14) provided stronger evidence of possible role in AD pathogenesis as they were also significantly associated with AD in previous expression quantitative trait loci analyses and/or mouse model studies.Discussion: Although the identified associations do not prove any definitive causal relationships with AD, they provide a list of prioritized genes for follow-up functional studies.

Leveraging DNA methylation quantitative-trait loci to characterize the relationship between metabolic traits and Alzheimer’s disease

2020 ◽  
Author(s):  
Di Liu ◽  
Zhiyuan Yu ◽  
Weijie Cao ◽  
Youxin Wang ◽  
Qun Meng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Sensitivity Analyses ◽  
Metabolic Traits ◽  
Trait Loci ◽  
The Relationship ◽  
Methylation Quantitative Trait Loci

Abstract Background: The relationship between DNA methylation, common metabolic risk and Alzheimer’s disease (AD) is not well understood.Methods: Summary statistics integrating DNA methylation quantitative trait loci (mQTLs) and several genome-wide association study data were used. Network with bidirectional mendelian randomization (MR) analysis was performed to examine the causal association among metabolic traits, DNA methylation and AD.Results: Our study showed that cis-mQTLs determined DNA methylation to higher total cholesterol (TC) was associated with higher AD risk (β [95% CI] =0.007 [0.002-0.013], P=0.005). The findings were robust in sensitivity analyses with different instrumental variables. We found no evidence to support causal associations of cis-mQTLs determined obesity and T2D with AD, and vice versa.Conclusion: Overall, our study showed that the cis-mQTLs determined DNA methylation to higher TC was associated with higher AD risk, whereas the relation of cis-mQTLs determined AD and metabolic dysregulation was unlikely to be causal.

P3-016: Overlap of gwas loci and expression quantitative trait loci (eQTL) in Alzheimer's disease

2015 ◽  
Vol 11 (7S_Part_13) ◽  
pp. P625-P626
Author(s):  
Nandini Badarinarayan ◽  
Rachel Raybould ◽  
Rebecca Sims ◽  
Amy Gerrish ◽  
Julie Williams
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Expression Quantitative Trait Loci ◽  
Trait Loci

scholarly journals Quantitative Trait Loci Associated with Rotylenchulus reniformis Host Suitability in Soybean

2020 ◽  
Vol 110 (9) ◽  
pp. 1511-1521
Author(s):  
Juliet Wilkes ◽  
Christopher Saski ◽  
Mariola Klepadlo ◽  
Benjamin Fallen ◽  
Paula Agudelo
Keyword(s):  
Quantitative Trait Loci ◽  
Qtl Analysis ◽  
Quantitative Trait ◽  
The United States ◽  
Host Suitability ◽  
Reniform Nematode ◽  
Rotylenchulus Reniformis ◽  
Chromosome 18 ◽  
Nematode Reproduction ◽  
Trait Loci

Reniform nematode (Rotylenchulus reniformis) is a yield-limiting pathogen of soybean (Glycine max) in the southeastern region of the United States. A population of 250 recombinant inbred lines (RIL) (F2:8) developed from a cross between reniform nematode resistant soybean cultivar Forrest and susceptible cultivar Williams 82 was utilized to identify regions associated with host suitability. A genetic linkage map was constructed using single-nucleotide polymorphism markers generated by genotyping-by-sequencing. The phenotype was measured in the RIL population and resistance was characterized using normalized and transformed nematode reproduction indices in an optimal univariate cluster analysis. Quantitative trait loci (QTL) analysis using normalized phenotype scores identified two QTLs on each arm of chromosome 18 (rrn-1 and rrn-2). The same QTL analysis performed with log10(x) transformed phenotype data also identified two QTLs: one on chromosome 18 overlapping the same region in the other analysis (rrn-1), and one on chromosome 11 (rrn-3). While rrn-1 and rrn-3 have been reported associated with reduced reproduction of reniform nematode, this is the first report of the rrn-2 region associated with host suitability to reniform nematode. The resistant parent allele at rrn-2 showed an inverse relationship with the resistance phenotype, correlating with an increase in nematode reproduction or host suitability. Several candidate genes within these regions corresponded with host plant defense systems. Interestingly, a characteristic pathogen resistance gene with a leucine-rich repeat was discovered within rrn-2. These genetic markers can be used by soybean breeders in marker-assisted selection to develop lines with resistance to reniform nematode.

scholarly journals PSV-13 Genetic parameters and quantitative trait loci for heat stress related traits in sheep

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 163-164
Author(s):  
Devin R Jacobs ◽  
Claudia E Silvera-Rojas ◽  
Jennifer M Bormann ◽  
Terry A Gipson ◽  
Arthur L Goetsch ◽  
...  
Keyword(s):  
Heat Stress ◽  
Quantitative Trait Loci ◽  
Rectal Temperature ◽  
Quantitative Trait ◽  
Fixed Effects ◽  
Univariate Analysis ◽  
Average Daily Gain ◽  
The United States ◽  
Nucleotide Polymorphisms ◽  
Trait Loci

Abstract Greater selection emphasis has been placed on efficiency than on fitness in livestock populations over the last several decades. Heat stress is a concern in production systems due to the negative effects on production, reproduction, and immunity. The objective of the study was to estimate variance components and identify quantitative trait loci (QTL) for heat stress related traits in sheep. A total of 125 Dorper, Katahdin, and St. Croix ewes originating from four regions of the United States were selected for the experiment. Animals were separated into four trials due to facility limitations. Data were collected for each trial over four consecutive two-week periods in an environmentally controlled facility with targeted heat load index (HLI) for daytime/nighttime of 70/70, 85/77, 90/77, and 95/81. Body weight was collected three times per week and rectal temperature was collected weekly. Black globe temperature and humidity were measured every 15 minutes. Animals were genotyped using the Illumina OvineSNP50 BeadChip. After quality control, 49,396 effective single nucleotide polymorphisms were included in the univariate analysis performed with the BLUPF90 suite of programs. Fixed effects in the models included region of origin, breed, trial, and age as a covariate. Traits analyzed included rectal temperature at 95 HLI (RT95), feed intake at 95 HLI (FI95), and average daily gain for the period for HLI between 90 and 95 (ADG). Heritabilities for RT95, FI95, and ADG were 0.35, 0.10, and 0.10, respectively. Largest effect QTL were identified on chromosomes 23, 9, and 6 for RT95, chromosomes 9, 2, and 20 for FI95, and chromosomes 6, 1, and 5 for ADG. Many of the regions identified have also been associated with weight and carcass traits in other studies, but few had obvious connections to the heat stress related response. In conclusion, results suggest selection could improve heat tolerance in sheep.

scholarly journals Summary-Based Methylome-Wide Association Analyses Suggest Potential Genetically Driven Epigenetic Heterogeneity of Alzheimer’s Disease

2020 ◽  
Vol 9 (5) ◽  
pp. 1489
Author(s):  
Alireza Nazarian ◽  
Anatoliy I. Yashin ◽  
Alexander M. Kulminski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Tissue Samples ◽  
Significance Level ◽  
Association Analyses ◽  
Functional Studies ◽  
Genome Wide ◽  
Summary Data

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with no curative treatment available. Exploring the genetic and non-genetic contributors to AD pathogenesis is essential to better understand its underlying biological mechanisms, and to develop novel preventive and therapeutic strategies. We investigated potential genetically driven epigenetic heterogeneity of AD through summary data-based Mendelian randomization (SMR), which combined results from our previous genome-wide association analyses with those from two publicly available methylation quantitative trait loci studies of blood and brain tissue samples. We found that 152 probes corresponding to 113 genes were epigenetically associated with AD at a Bonferroni-adjusted significance level of 5.49E-07. Of these, 10 genes had significant probes in both brain-specific and blood-based analyses. Comparing males vs. females and hypertensive vs. non-hypertensive subjects, we found that 22 and 79 probes had group-specific associations with AD, respectively, suggesting a potential role for such epigenetic modifications in the heterogeneous nature of AD. Our analyses provided stronger evidence for possible roles of four genes (i.e., AIM2, C16orf80, DGUOK, and ST14) in AD pathogenesis as they were also transcriptionally associated with AD. The identified associations suggest a list of prioritized genes for follow-up functional studies and advance our understanding of AD pathogenesis.

scholarly journals Influence of Woodsmoke Exposure on Molecular Mechanisms Underlying Alzheimer’s Disease: Existing Literature and Gaps in Our Understanding

2020 ◽  
Vol 13 ◽  
pp. 251686572095487
Author(s):  
Adam Schuller ◽  
Luke Montrose
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Ambient Air ◽  
The United States ◽  
Ambient Air Pollution ◽  
Current Status

Woodsmoke poses a significant health risk as a growing component of ambient air pollution in the United States. While there is a long history of association between woodsmoke exposure and diseases of the respiratory, circulatory, and cardiovascular systems, recent evidence has linked woodsmoke exposure to cognitive dysfunction, including Alzheimer’s disease dementia. Alzheimer’s disease is a progressive neurodegenerative disorder with largely idiopathic origins and no known cure. Here, we explore the growing body of literature which relates woodsmoke-generated and ambient air pollution particulate matter exposure to Alzheimer’s disease (AD) onset or exacerbation, in the context of an inflammation-centric view of AD. Epigenetic modifications, specifically changes in DNA methylation patterns, are well documented following woodsmoke exposure and have been shown to influence disease-favoring inflammatory cascades, induce oxidative stress, and modulate the immune response in vitro, in vivo, and in humans following exposure to air pollution. Though the current status of the literature does not allow us to draw definitive conclusions linking these events, this review highlights the need for additional work to fill gaps in our understanding of the directionality, causality, and susceptibility throughout the life course.

Whole genome fine mapping of quantitative trait loci for ultrasound and carcass merit traits in beef cattle

2011 ◽  
Vol 91 (1) ◽  
pp. 61-73 ◽  
Author(s):  
Sungael Nalaila ◽  
Paul Stothard ◽  
Stephen Moore ◽  
Zhiquan Wang ◽  
Changxi Li
Keyword(s):  
Quantitative Trait Loci ◽  
Beef Cattle ◽  
Fine Mapping ◽  
Quantitative Trait ◽  
Snp Markers ◽  
Whole Genome ◽  
Association Analyses ◽  
University Of Alberta ◽  
Trait Loci ◽  
Carcass Merit

Nalaila, S. M., Stothard, P., Moore, S. S., Wang, Z. and Li, C. 2011. Whole genome fine mapping of quantitative trait loci for ultrasound and carcass merit traits in beef cattle. Can. J. Anim. Sci. 91: 61–73. Quantitative trait loci (QTL) mapped to large chromosomal regions have limited utility as DNA markers for marker-assisted selection (MAS) and are less informative as a reference for the identification of the underlying causative quantitative trait nucleotides (QTN). The objective of this study was to conduct a whole genome fine mapping of QTL for ultrasound and carcass merit traits in beef cattle using a greater density of single nucleotide polymorphism (SNP) markers, and to identify SNP markers within the QTL regions that are associated with the traits. A total of 418 steers from 28 sires were used in this study with nine ultrasound and seven carcass merit traits that were collected as part of a feedlot trial conducted from 2003 to 2005 at the University of Alberta Kinsella ranch. Sires and their progeny were genotyped for a total of 4592 SNP markers distributed across all 29 bovine autosomes (BTA). Across-family analyses detected 12 QTL for five ultrasound traits on nine chromosomes and 18 QTL for six carcass merit traits on 10 chromosomes (P<0.05). Within-family analyses identified 78 significant QTL for nine ultrasound and seven carcass merit traits (P<0.01). The use of a denser panel of SNP markers allowed fine mapping of QTL to smaller chromosomal regions ranging from 0.6 to 11 cM compared with relatively larger QTL regions of 4 to 24 cM reported in previous studies. Furthermore, single SNP marker association analyses identified 22 SNPs that were significantly associated with three ultrasound and four carcass merit traits under 12 QTL regions (P<0.05). These identified SNP markers significantly associated with the traits under the fine mapped QTL regions provide genomic tools for potential application of MAS and a reference to assist with the identification of QTN causing variations in ultrasound and carcass merit traits in beef cattle.

scholarly journals Two Independent Quantitative Trait Loci Are Responsible for Novel Resistance to Beet curly top virus in Common Bean Landrace G122

2010 ◽  
Vol 100 (10) ◽  
pp. 972-978 ◽  
Author(s):  
Richard C. Larsen ◽  
Chester J. Kurowski ◽  
Phillip N. Miklas
Keyword(s):  
Quantitative Trait Loci ◽  
Linkage Group ◽  
Common Bean ◽  
Quantitative Trait ◽  
Rapd Marker ◽  
The United States ◽  
Effective Control ◽  
Minor Effect ◽  
Beet Curly Top Virus ◽  
Trait Loci

Beet curly top virus, often referred to as Curly top virus (CTV), is an important virus disease of common bean in the semiarid regions of the United States, Canada, and Mexico and the only effective control is genetic resistance. Our objective was to determine if dry bean landrace G122, which lacks the Bct gene for resistance to CTV, contains novel resistance to the virus. Two populations, GT-A and GT-B, consisting of 98 F5:7 recombinant inbred lines (RILs) in total were derived from a cross between G122 and the susceptible variety Taylor Horticultural and evaluated for phenotypic response to natural CTV field infection. Genetic analyses revealed random amplified polymorphism DNA (RAPD) markers associated with a major-effect quantitative trait loci (QTL) from G122 which exhibited stable expression across 3 years in both populations. Phenotypic variation explained by the QTL in GT-A (37.6%) was greater than in GT-B (20.4%). RAPD marker Q14.973 was converted to a sequence-characterized amplified region (SCAR) and designated SQ14.973. The SCAR was used to locate the QTL on linkage group 6 of the Phaseolus core map. A survey of 74 common bean cultivars and breeding lines revealed SQ14.973 would be widely useful for marker-assisted selection of the QTL. An additional minor-effect QTL from G122 was detected on linkage group 7. G122 was determined to possess novel resistance to CTV conditioned by at least two genes, one with major the other minor effect.

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