scholarly journals Multiple sclerosis risk variants regulate gene expression in innate and adaptive immune cells

2020 ◽  
Vol 3 (7) ◽  
pp. e202000650 ◽  
Author(s):  
Melissa M Gresle ◽  
Margaret A Jordan ◽  
Jim Stankovich ◽  
Tim Spelman ◽  
Laura J Johnson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Immune Cell ◽  
Cell Types ◽  
Expression Quantitative Trait Loci ◽  
Nucleotide Polymorphisms ◽  
Adaptive Immune Cells ◽  
Trait Loci

At least 200 single-nucleotide polymorphisms (SNPs) are associated with multiple sclerosis (MS) risk. A key function that could mediate SNP-encoded MS risk is their regulatory effects on gene expression. We performed microarrays using RNA extracted from purified immune cell types from 73 untreated MS cases and 97 healthy controls and then performed Cis expression quantitative trait loci mapping studies using additive linear models. We describe MS risk expression quantitative trait loci associations for 129 distinct genes. By extending these models to include an interaction term between genotype and phenotype, we identify MS risk SNPs with opposing effects on gene expression in cases compared with controls, namely, rs2256814 MYT1 in CD4 cells (q = 0.05) and rs12087340 RF00136 in monocyte cells (q = 0.04). The rs703842 SNP was also associated with a differential effect size on the expression of the METTL21B gene in CD8 cells of MS cases relative to controls (q = 0.03). Our study provides a detailed map of MS risk loci that function by regulating gene expression in cell types relevant to MS.

Promoter-Interacting Expression Quantitative Trait Loci (pieQTLs) in Human Immune Cell Types

2019 ◽  
Author(s):  
Vivek Chandra ◽  
Sourya Bhattacharyya ◽  
Benjamin J. Schmiedel ◽  
Ariel Madrigal ◽  
Stephanie Fotsing ◽  
...  
Keyword(s):  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Immune Cell ◽  
Cell Types ◽  
Expression Quantitative Trait Loci ◽  
Trait Loci ◽  
Human Immune

scholarly journals Characterization of expression quantitative trait loci in extensively phenotyped pedigrees ascertained for bipolar disorder

2015 ◽  
Author(s):  
Christine Peterson ◽  
Susan Service ◽  
Anna Jasinska ◽  
Fuying Gao ◽  
Ivette Zelaya ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bipolar Disorder ◽  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Complex Traits ◽  
Expression Quantitative Trait Loci ◽  
Genome Wide ◽  
Wide Range ◽  
Trait Loci

The observation that variants regulating gene expression (expression quantitative trait loci, eQTL) are at a high frequency among SNPs associated with complex traits has made the genome-wide characterization of gene expression an important tool in genetic mapping studies of such traits. As part of a study to identify genetic loci contributing to bipolar disorder and a wide range of BP-related quantitative traits in members of 26 pedigrees from Costa Rica and Colombia, we measured gene expression in lymphoblastoid cell lines derived from 786 pedigree members. The study design enabled us to comprehensively reconstruct the genetic regulatory network in these families, provide estimates of heritability, identify eQTL, evaluate missing heritability for the eQTL, and quantify the number of different alleles contributing to any given locus.

scholarly journals Identification and application of plasmatic microRNA expression quantitative trait loci (miR-QTL) at first trimester of pregnancy

2021 ◽  
Author(s):  
Frédérique White ◽  
Marika Groleau ◽  
Samuel Côté ◽  
Cécilia Légaré ◽  
Kathrine Thibeault ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantitative Trait Loci ◽  
Instrumental Variables ◽  
Quantitative Trait ◽  
Molecular Mechanisms ◽  
First Trimester ◽  
Risk Scores ◽  
Expression Quantitative Trait Loci ◽  
Trait Loci ◽  
First Trimester Of Pregnancy

AbstractBackgroundMicroRNAs (miRNAs) are a class of small non-coding RNAs regulating gene expression. They are involved in many biological processes, including adaptation to pregnancy. The identification of genetic variants associated with gene expression, known as expression quantitative trait loci (eQTL), helps to understand the underlying molecular mechanisms and determinants of complex diseases. Using data from the prospective pre-birth Gen3G cohort, we investigated associations between maternal genotypes and plasmatic miRNA levels measured during the first trimester of pregnancy of 369 women.ResultsAssessing the associations between about 2 million SNPs and miRNA proximal pairs using best practices from the GTEx consortium, a total of 22,140 significant eQTLs involving 147 unique miRNAs were identified. Elastic-net regressions were applied to select the most relevant SNPs to build genetic risk scores (GRS) for each of these 147 miRNAs. For about half of the circulating miRNAs, the GRS captured >10% of the variance abundance. As a demonstration of the usefulness of the identified eQTLs and derived GRS, we used the GRSs as instrumental variables to test for association between the circulating levels of miRNAs quantified before the 16th week of pregnancy and the development of pregnancy complications (gestational diabetes [GDM] or pre-eclampsia [PE]) developing more than three months later on average. Using predicted miRNA levels derived from instrumental variables, we found 18 significant associations of miRNAs with potential support of causal inference for GDM or PE.ConclusionsOur results represent a valuable resource to understand miRNA regulation and highlight the potential of genetic instruments in predicting circulating miRNA levels and their possible contribution in disease development.

scholarly journals Integrated Genome-Wide Analysis of MicroRNA Expression Quantitative Trait Loci in Pig Longissimus Dorsi Muscle

2021 ◽  
Vol 12 ◽  
Author(s):  
Kaitlyn R. Daza ◽  
Deborah Velez-Irizarry ◽  
Sebastian Casiró ◽  
Juan P. Steibel ◽  
Nancy E. Raney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantitative Trait Loci ◽  
Mirna Expression ◽  
Quantitative Trait ◽  
Complex Traits ◽  
Carcass Composition ◽  
Longissimus Dorsi ◽  
Expression Quantitative Trait Loci ◽  
Genome Wide ◽  
Trait Loci

Determining mechanisms regulating complex traits in pigs is essential to improve the production efficiency of this globally important protein source. MicroRNAs (miRNAs) are a class of non-coding RNAs known to post-transcriptionally regulate gene expression affecting numerous phenotypes, including those important to the pig industry. To facilitate a more comprehensive understanding of the regulatory mechanisms controlling growth, carcass composition, and meat quality phenotypes in pigs, we integrated miRNA and gene expression data from longissimus dorsi muscle samples with genotypic and phenotypic data from the same animals. We identified 23 miRNA expression Quantitative Trait Loci (miR-eQTL) at the genome-wide level and examined their potential effects on these important production phenotypes through miRNA target prediction, correlation, and colocalization analyses. One miR-eQTL miRNA, miR-874, has target genes that colocalize with phenotypic QTL for 12 production traits across the genome including backfat thickness, dressing percentage, muscle pH at 24 h post-mortem, and cook yield. The results of our study reveal genomic regions underlying variation in miRNA expression and identify miRNAs and genes for future validation of their regulatory effects on traits of economic importance to the global pig industry.

scholarly journals Common Expression Quantitative Trait Loci Shared by Histone Genes

2017 ◽  
Vol 2017 ◽  
pp. 1-14
Author(s):  
Hanseol Kim ◽  
Yujin Suh ◽  
Chaeyoung Lee
Keyword(s):  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Genome Wide Association Study ◽  
Histone Genes ◽  
Expression Quantitative Trait Loci ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
A Genome ◽  
Trait Loci ◽  
Cycle Dependent

A genome-wide association study (GWAS) was conducted to examine expression quantitative trait loci (eQTLs) for histone genes. We examined common eQTLs for multiple histone genes in 373 European lymphoblastoid cell lines (LCLs). A linear regression model was employed to identify single-nucleotide polymorphisms (SNPs) associated with expression of the histone genes, and the number of eQTLs was determined by linkage disequilibrium analysis. Additional associations of the identified eQTLs with other genes were also examined. We identified 31 eQTLs for 29 histone genes through genome-wide analysis using 29 histone genes (P<2.97×10−10). Among them, 12 eQTLs were associated with the expression of multiple histone genes. Transcriptome-wide association analysis using the identified eQTLs showed their associations with additional 80 genes (P<4.75×10−6). In particular, expression of RPPH1, SCARNA2, and SCARNA7 genes was associated with 26, 25, and 23 eQTLs, respectively. This study suggests that histone genes shared 12 common eQTLs that might regulate cell cycle-dependent transcription of histone and other genes. Further investigations are needed to elucidate the transcriptional mechanisms of these genes.

scholarly journals Identification of Distant Regulatory Elements Using Expression Quantitative Trait Loci Mapping for Heat-Responsive Genes in Oysters

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1040
Author(s):  
Kexin Zhang ◽  
Jinpeng Wang ◽  
Fangfang Ding ◽  
Ruihui Shi ◽  
Wei Wang ◽  
...  
Keyword(s):  
Climate Change ◽  
Gene Expression ◽  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Target Genes ◽  
Future Climate Change ◽  
Climate Change Scenarios ◽  
Expression Quantitative Trait Loci ◽  
Independent Family ◽  
Trait Loci

Many marine ectotherms, especially those inhabiting highly variable intertidal zones, develop high phenotypic plasticity in response to rapid climate change by modulating gene expression levels. Herein, we examined the regulatory architecture of heat-responsive gene expression plasticity in oysters using expression quantitative trait loci (eQTL) analysis. Using a backcross family of Crassostrea gigas and its sister species Crassostrea angulata under acute stress, 56 distant regulatory regions accounting for 6–26.6% of the gene expression variation were identified for 19 heat-responsive genes. In total, 831 genes and 164 single nucleotide polymorphisms (SNPs) that could potentially regulate expression of the target genes were screened in the eQTL region. The association between three SNPs and the corresponding target genes was verified in an independent family. Specifically, Marker13973 was identified for heat shock protein (HSP) family A member 9 (HspA9). Ribosomal protein L10a (RPL10A) was detected approximately 2 kb downstream of the distant regulatory SNP. Further, Marker14346-48 and Marker14346-85 were in complete linkage disequilibrium and identified for autophagy-related gene 7 (ATG7). Nuclear respiratory factor 1 (NRF1) was detected approximately 3 kb upstream of the two SNPs. These results suggested regulatory relationships between RPL10A and HSPA9 and between NRF1 and ATG7. Our findings indicate that distant regulatory mutations play an important role in the regulation of gene expression plasticity by altering upstream regulatory factors in response to heat stress. The identified eQTLs provide candidate biomarkers for predicting the persistence of oysters under future climate change scenarios.

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