Bioinformatic and Genetic Association Analysis of MicroRNA Target Sites in One-Carbon Metabolism Genes

<sec><title>Study Design</title>A prospective genetic association study.</sec><sec><title>Purpose</title>The etiology of Modic changes (MCs) is unclear. Recently, the role of genetic factors in the etiology of MCs has been evaluated. However, studies with a larger patient subset are lacking, and candidate genes involved in other disc degeneration phenotypes have not been evaluated. We studied the prevalence of MCs and genetic association of 41 candidate genes in a large Indian cohort.</sec><sec><title>Overview of Literature</title>MCs are vertebral endplate signal changes predominantly observed in the lumbar spine. A significant association between MCs and lumbar disc degeneration and nonspecific low back pain has been described, with the etiopathogenesis implicating various mechanical, infective, and biochemical factors.</sec><sec><title>Methods</title>We studied 809 patients using 1.5-T magnetic resonance imaging to determine the prevalence, patterns, distribution, and type of lumbar MCs. Genetic association analysis of 71 single nucleotide polymorphisms (SNPs) of 41 candidate genes was performed based on the presence or absence of MCs. SNPs were genotyped using the Sequenome platform, and an association test was performed using PLINK software.</sec><sec><title>Results</title>The mean age of the study population (n=809) was 36.7±10.8 years. Based on the presence of MCs, the cohort was divided into 702 controls and 107 cases (prevalence, 13%). MCs were more commonly present in the lower (149/251, 59.4%) than in the upper (102/251, 40.6%) endplates. L4–5 endplates were the most commonly affected levels (30.7%). Type 2 MCs were the most commonly observed pattern (n=206, 82%). The rs2228570 SNP of VDR (<italic>p</italic>=0.02) and rs17099008 SNP of MMP20 (<italic>p</italic>=0.03) were significantly associated with MCs.</sec><sec><title>Conclusions</title>Genetic polymorphisms of SNPs of VDR and MMP20 were significantly associated with MCs. Understanding the etiopathogenetic mechanisms of MCs is important for planning preventive and therapeutic strategies.</sec>

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Providing Context and Interpretability to Genetic Association Analysis Results Using the KGraph

Computational Methods for Genetics of Complex Traits - Advances in Genetics ◽

10.1016/b978-0-12-380862-2.00008-4 ◽

2010 ◽

pp. 181-193

Author(s):

Reagan J. Kelly ◽

Jennifer A. Smith ◽

Sharon L.R. Kardia

Keyword(s):

Genetic Association ◽

Association Analysis ◽

Genetic Association Analysis

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Genetic Association Analysis of Cell Cycle Regulators Reveals YWHAZ Has Prognostic Significance in Prostate Cancer

Cancer Genomics & Proteomics ◽

10.21873/cgp.20181 ◽

2020 ◽

Vol 17 (2) ◽

pp. 209-216 ◽

Cited By ~ 1

Author(s):

CHIA-CHENG YU ◽

LIH-CHYANG CHEN ◽

WEN-HSIN LIN ◽

VICTOR C. LIN ◽

CHAO-YUAN HUANG ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Genetic Association ◽

Association Analysis ◽

Prognostic Significance ◽

Cell Cycle Regulators ◽

Genetic Association Analysis

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Diverse tumour susceptibility in Collaborative Cross mice: identification of a new mouse model for human gastric tumourigenesis

Gut ◽

10.1136/gutjnl-2018-316691 ◽

2019 ◽

Vol 68 (11) ◽

pp. 1942-1952 ◽

Cited By ~ 5

Author(s):

Pin Wang ◽

Yunshan Wang ◽

Sasha A Langley ◽

Yan-Xia Zhou ◽

Kuang-Yu Jen ◽

...

Keyword(s):

Inflammatory Response ◽

Mouse Model ◽

Rna Sequencing ◽

Genetic Association ◽

Association Analysis ◽

Collaborative Cross ◽

Sequencing Analysis ◽

Genetic Association Analysis ◽

Mouse Population ◽

Wide Range

ObjectiveThe Collaborative Cross (CC) is a mouse population model with diverse and reproducible genetic backgrounds used to identify novel disease models and genes that contribute to human disease. Since spontaneous tumour susceptibility in CC mice remains unexplored, we assessed tumour incidence and spectrum.DesignWe monitored 293 mice from 18 CC strains for tumour development. Genetic association analysis and RNA sequencing were used to identify susceptibility loci and candidate genes. We analysed genomes of patients with gastric cancer to evaluate the relevance of genes identified in the CC mouse model and measured the expression levels of ISG15 by immunohistochemical staining using a gastric adenocarcinoma tissue microarray. Association of gene expression with overall survival (OS) was assessed by Kaplan-Meier analysis.ResultsCC mice displayed a wide range in the incidence and types of spontaneous tumours. More than 40% of CC036 mice developed gastric tumours within 1 year. Genetic association analysis identified Nfκb1 as a candidate susceptibility gene, while RNA sequencing analysis of non-tumour gastric tissues from CC036 mice showed significantly higher expression of inflammatory response genes. In human gastric cancers, the majority of human orthologues of the 166 mouse genes were preferentially altered by amplification or deletion and were significantly associated with OS. Higher expression of the CC036 inflammatory response gene signature is associated with poor OS. Finally, ISG15 protein is elevated in gastric adenocarcinomas and correlated with shortened patient OS.ConclusionsCC strains exhibit tremendous variation in tumour susceptibility, and we present CC036 as a spontaneous laboratory mouse model for studying human gastric tumourigenesis.

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