Systematic pathway-analysis of kinesin protein family (KIF) using genome-wide SNP data in patients with myocardial infarction: Genetic variation in KIFC3 gene associates with myocardial infarction

Background: Myocardial infarction (MI) is one of the leading threats to human health. N6-methyladenosine (m6A) modification, as a pivotal regulator of messenger RNA stability, protein expression, and cellular processes, exhibits important roles in the development of cardiac remodeling and cardiomyocyte contractile function.Methods: The expression levels of m6A regulators were analyzed using the GSE5406 database. We analyzed genome-wide association study data and single-cell sequencing data to confirm the functional importance of m6A regulators in MI. Three molecular subtypes with different clinical characteristics were established to tailor treatment strategies for patients with MI. We applied pathway analysis and differentially expressed gene (DEG) analysis to study the changes in gene expression and identified four common DEGs. Furthermore, we constructed the protein–protein interaction network and confirmed several hub genes in three clusters of MI. To lucubrate the potential functions, we performed a ClueGO analysis of these hub networks.Results: In this study, we identified that the levels of FTO, YTHDF3, ZC3H13, and WTAP were dramatically differently expressed in MI tissues compared with controls. Bioinformatics analysis showed that DEGs in MI were significantly related to modulating calcium signaling and chemokine signaling, and m6A regulators were related to regulating glucose measurement and elevated blood glucose levels. Furthermore, genome-wide association study data analysis showed that WTAP single-nucleotide polymorphism was significantly related to the progression of MI. In addition, single-cell sequencing found that WTAP is widely expressed in the heart tissues. Moreover, we conducted consensus clustering for MI in view of the dysregulated m6A regulators’ expression in MI. According to the expression levels, we found MI patients could be clustered into three subtypes. Pathway analysis showed the DEGs among different clusters in MI were assigned to HIF-1, IL-17, MAPK, PI3K-Akt signaling pathways, etc. The module analysis detected several genes, including BAG2, BAG3, MMP2, etc. We also found that MI-related network was significantly related to positive and negative regulation of angiogenesis and response to heat. The hub networks in MI clusters were significantly related to antigen processing and ubiquitin-mediated proteolysis, RNA splicing, and stability, indicating that these processes may contribute to the development of MI.Conclusion: Collectively, our study could provide more information for understanding the roles of m6A in MI, which may provide a novel insight into identifying biomarkers for MI treatment and diagnosis.

Download Full-text

Genetic variation and health in rural Caribbean village

10.32469/10355/79506 ◽

2020 ◽

Author(s):

◽

Monica H. Keith

Keyword(s):

Population Structure ◽

Genetic Variation ◽

Genomic Region ◽

Ancestral Population ◽

Small Scale ◽

Growth Data ◽

Mixed Effect ◽

Snp Data ◽

Genome Wide ◽

Variable Nature

Bwa Mawego is a small-scale horticultural community (~500 people) on the island of Dominica that has been the site of a longitudinal health research project for more than 30 years. Cardiovascular diseases and metabolic health are growing local concerns. Here we analyze longitudinal growth data, cardiometabolic metrics, and genome-wide single nucleotide polymorphism (SNP) data from this population to investigate sources of variation in anthropometric and cardiometabolic outcomes. Mixed effect heritability models indicate that (1) variation in body mass index (BMI) is significantly shaped by genetic variation, and (2) variation between longitudinal BMI curves has not been consistently impacted by secular environmental trends from 1997 2017. In order to assess genetic variation in more detail, we first characterize the population structure and admixture in this Caribbean community using high-density SNP data and global reference samples in the Human Genome Diversity Panel. We detect four distinct family clusters and admixture from African, European, and Amerindian ancestral populations that occurred 5-6 generations ago (~130-150 years). Amerindian haplotypes represented in Bwa Mawego associate with deeply diverged lineages in Karitiana and Surui peoples, highlighting the regionally variable nature of admixture throughout the Caribbean and unique historical outcomes in Dominica. Genome-wide association tests of cardiometabolic phenotypes identify a genomic region of interest downstream of the ANK3 gene that associates with BMI in Bwa Mawego, after controlling for confounding variation from ancestral population structure and relatedness. Any functional relationship between ANK3 and BMI is currently uncharacterized, and there is unique potential to further explore complex gene-environment-phenotype landscapes in Bwa Mawego.

Download Full-text

The Pharmacogenetics of Statin Therapy on Clinical Events: No Evidence that Genetic Variation Affects Statin Response on Myocardial Infarction

Frontiers in Pharmacology ◽

10.3389/fphar.2021.679857 ◽

2022 ◽

Vol 12 ◽

Author(s):

Stella Trompet ◽

Iris Postmus ◽

Helen R. Warren ◽

Raymond Noordam ◽

Roelof A. J. Smit ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiovascular Disease ◽

Genetic Variation ◽

Statin Therapy ◽

Risk Reduction ◽

Meta Analysis ◽

Clinical Events ◽

Genome Wide ◽

Stage 1 ◽

Statin Response

Background: The pharmacogenetic effect on cardiovascular disease reduction in response to statin treatment has only been assessed in small studies. In a pharmacogenetic genome wide association study (GWAS) analysis within the Genomic Investigation of Statin Therapy (GIST) consortium, we investigated whether genetic variation was associated with the response of statins on cardiovascular disease risk reduction.Methods: The investigated endpoint was incident myocardial infarction (MI) defined as coronary heart disease death and definite and suspect non-fatal MI. For imputed single nucleotide polymorphisms (SNPs), regression analysis was performed on expected allelic dosage and meta-analysed with a fixed-effects model, inverse variance weighted meta-analysis. All SNPs with p-values <5.0 × 10−4 in stage 1 GWAS meta-analysis were selected for further investigation in stage-2. As a secondary analysis, we extracted SNPs from the Stage-1 GWAS meta-analysis results based on predefined hypotheses to possibly modifying the effect of statin therapy on MI.Results: In stage-1 meta-analysis (eight studies, n = 10,769, 4,212 cases), we observed no genome-wide significant results (p < 5.0 × 10−8). A total of 144 genetic variants were followed-up in the second stage (three studies, n = 1,525, 180 cases). In the combined meta-analysis, no genome-wide significant hits were identified. Moreover, none of the look-ups of SNPs known to be associated with either CHD or with statin response to cholesterol levels reached Bonferroni level of significance within our stage-1 meta-analysis.Conclusion: This GWAS analysis did not provide evidence that genetic variation affects statin response on cardiovascular risk reduction. It does not appear likely that genetic testing for predicting effects of statins on clinical events will become a useful tool in clinical practice.

Download Full-text

Pathway Analysis for Genome-wide Genetic Variation Data: Analytic Principles, Latest Developments, and New Opportunities

Journal of Genetics and Genomics ◽

10.1016/j.jgg.2021.01.007 ◽

2021 ◽

Author(s):

Micah Silberstein ◽

Nicholas Nesbit ◽

Jacquelyn Cai ◽

Phil H. Lee

Keyword(s):

Genetic Variation ◽

Pathway Analysis ◽

Genome Wide ◽

Variation Data ◽

Data Analytic

Download Full-text

Genome-wide SNPs redefines species boundaries and conservation units in the freshwater mussel genus Cyprogenia of North America

Scientific Reports ◽

10.1038/s41598-021-90325-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kyung Seok Kim ◽

Kevin J. Roe

Keyword(s):

Phylogenetic Analyses ◽

Freshwater Mussel ◽

Conservation Strategies ◽

Nucleotide Polymorphisms ◽

Conservation Units ◽

Genetic Structuring ◽

The North ◽

Snp Data ◽

Genome Wide ◽

Significant Difference

AbstractDetailed information on species delineation and population genetic structure is a prerequisite for designing effective restoration and conservation strategies for imperiled organisms. Phylogenomic and population genomic analyses based on genome-wide double digest restriction-site associated DNA sequencing (ddRAD-Seq) data has identified three allopatric lineages in the North American freshwater mussel genus Cyprogenia. Cyprogenia stegaria is restricted to the Eastern Highlands and displays little genetic structuring within this region. However, two allopatric lineages of C. aberti in the Ozark and Ouachita highlands exhibit substantial levels (mean uncorrected FST = 0.368) of genetic differentiation and each warrants recognition as a distinct evolutionary lineage. Lineages of Cyprogenia in the Ouachita and Ozark highlands are further subdivided reflecting structuring at the level of river systems. Species tree inference and species delimitation in a Bayesian framework using single nucleotide polymorphisms (SNP) data supported results from phylogenetic analyses, and supports three species of Cyprogenia over the currently recognized two species. A comparison of SNPs generated from both destructively and non-destructively collected samples revealed no significant difference in the SNP error rate, quality and amount of ddRAD sequence reads, indicating that nondestructive or trace samples can be effectively utilized to generate SNP data for organisms for which destructive sampling is not permitted.

Download Full-text

Genomic Analyses of Globodera pallida, A Quarantine Agricultural Pathogen in Idaho

Pathogens ◽

10.3390/pathogens10030363 ◽

2021 ◽

Vol 10 (3) ◽

pp. 363

Author(s):

Sulochana K. Wasala ◽

Dana K. Howe ◽

Louise-Marie Dandurand ◽

Inga A. Zasada ◽

Dee R. Denver

Keyword(s):

Genetic Variation ◽

Potato Production ◽

Globodera Pallida ◽

Fixation Index ◽

Parasitic Nematodes ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Genome Wide ◽

Field Samples ◽

Multiple Introduction

Globodera pallida is among the most significant plant-parasitic nematodes worldwide, causing major damage to potato production. Since it was discovered in Idaho in 2006, eradication efforts have aimed to contain and eradicate G. pallida through phytosanitary action and soil fumigation. In this study, we investigated genome-wide patterns of G. pallida genetic variation across Idaho fields to evaluate whether the infestation resulted from a single or multiple introduction(s) and to investigate potential evolutionary responses since the time of infestation. A total of 53 G. pallida samples (~1,042,000 individuals) were collected and analyzed, representing five different fields in Idaho, a greenhouse population, and a field in Scotland that was used for external comparison. According to genome-wide allele frequency and fixation index (Fst) analyses, most of the genetic variation was shared among the G. pallida populations in Idaho fields pre-fumigation, indicating that the infestation likely resulted from a single introduction. Temporal patterns of genome-wide polymorphisms involving (1) pre-fumigation field samples collected in 2007 and 2014 and (2) pre- and post-fumigation samples revealed nucleotide variants (SNPs, single-nucleotide polymorphisms) with significantly differentiated allele frequencies indicating genetic differentiation. This study provides insights into the genetic origins and adaptive potential of G. pallida invading new environments.

Download Full-text

Genomic variation in the American pika: signatures of geographic isolation and implications for conservation

BMC Ecology and Evolution ◽

10.1186/s12862-020-01739-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Kelly B. Klingler ◽

Joshua P. Jahner ◽

Thomas L. Parchman ◽

Chris Ray ◽

Mary M. Peacock

Keyword(s):

Genetic Variation ◽

Genetic Structure ◽

Sierra Nevada ◽

Spatial Genetic Structure ◽

Spatial Scales ◽

Thermal Sensitivity ◽

Genomic Variation ◽

Genome Wide ◽

A Genome ◽

American Pika

Abstract Background Distributional responses by alpine taxa to repeated, glacial-interglacial cycles throughout the last two million years have significantly influenced the spatial genetic structure of populations. These effects have been exacerbated for the American pika (Ochotona princeps), a small alpine lagomorph constrained by thermal sensitivity and a limited dispersal capacity. As a species of conservation concern, long-term lack of gene flow has important consequences for landscape genetic structure and levels of diversity within populations. Here, we use reduced representation sequencing (ddRADseq) to provide a genome-wide perspective on patterns of genetic variation across pika populations representing distinct subspecies. To investigate how landscape and environmental features shape genetic variation, we collected genetic samples from distinct geographic regions as well as across finer spatial scales in two geographically proximate mountain ranges of eastern Nevada. Results Our genome-wide analyses corroborate range-wide, mitochondrial subspecific designations and reveal pronounced fine-scale population structure between the Ruby Mountains and East Humboldt Range of eastern Nevada. Populations in Nevada were characterized by low genetic diversity (π = 0.0006–0.0009; θW = 0.0005–0.0007) relative to populations in California (π = 0.0014–0.0019; θW = 0.0011–0.0017) and the Rocky Mountains (π = 0.0025–0.0027; θW = 0.0021–0.0024), indicating substantial genetic drift in these isolated populations. Tajima’s D was positive for all sites (D = 0.240–0.811), consistent with recent contraction in population sizes range-wide. Conclusions Substantial influences of geography, elevation and climate variables on genetic differentiation were also detected and may interact with the regional effects of anthropogenic climate change to force the loss of unique genetic lineages through continued population extirpations in the Great Basin and Sierra Nevada.

Download Full-text

Genome-wide SNP data unravel the ancestry and signatures of divergent selection in Ghurrah pigs of India

Livestock Science ◽

10.1016/j.livsci.2021.104587 ◽

2021 ◽

pp. 104587

Author(s):

Arnav Mehrotra ◽

Bharat Bhushan ◽

Karthikeyan A ◽

Akansha Singh ◽

Snehasmita Panda ◽

...

Keyword(s):

Divergent Selection ◽

Snp Data ◽

Genome Wide

Download Full-text