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Meta-Analyses of Splicing and Expression Quantitative Trait Loci Identified Susceptibility Genes of Glioma

Overview of attention for article published in Frontiers in Genetics, April 2021
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Title
Meta-Analyses of Splicing and Expression Quantitative Trait Loci Identified Susceptibility Genes of Glioma
Published in
Frontiers in Genetics, April 2021
DOI 10.3389/fgene.2021.609657
Pubmed ID
Authors

C. Pawan K. Patro, Darryl Nousome, The Glioma International Case Control Study, Rose K. Lai, Elizabeth B. Claus, Dora Il’yasova, Joellen Schildkraut, Jill S. Barnholtz-Sloan, Sara H. Olson, Jonine L. Bernstein, Christoffer Johansen, Robert B. Jenkins, Beatrice S. Melin, Margaret R. Wrensch, Richard S. Houlston, Melissa L. Bondy

Abstract

The functions of most glioma risk alleles are unknown. Very few studies had evaluated expression quantitative trait loci (eQTL), and insights of susceptibility genes were limited due to scarcity of available brain tissues. Moreover, no prior study had examined the effect of glioma risk alleles on alternative RNA splicing. This study explored splicing quantitative trait loci (sQTL) as molecular QTL and improved the power of QTL mapping through meta-analyses of both cis eQTL and sQTL. We first evaluated eQTLs and sQTLs of the CommonMind Consortium (CMC) and Genotype-Tissue Expression Project (GTEx) using genotyping, or whole-genome sequencing and RNA-seq data. Alternative splicing events were characterized using an annotation-free method that detected intron excision events. Then, we conducted meta-analyses by pooling the eQTL and sQTL results of CMC and GTEx using the inverse variance-weighted model. Afterward, we integrated QTL meta-analysis results (Q < 0.05) with the Glioma International Case Control Study (GICC) GWAS meta-analysis (case:12,496, control:18,190), using a summary statistics-based mendelian randomization (SMR) method. Between CMC and GTEx, we combined the QTL data of 354 unique individuals of European ancestry. SMR analyses revealed 15 eQTLs in 11 loci and 32 sQTLs in 9 loci relevant to glioma risk. Two loci only harbored sQTLs (1q44 and 16p13.3). In seven loci, both eQTL and sQTL coexisted (2q33.3, 7p11.2, 11q23.3 15q24.2, 16p12.1, 20q13.33, and 22q13.1), but the target genes were different for five of these seven loci. Three eQTL loci (9p21.3, 20q13.33, and 22q13.1) and 4 sQTL loci (11q23.3, 16p13.3, 16q12.1, and 20q13.33) harbored multiple target genes. Eight target genes of sQTLs (C2orf80, SEC61G, TMEM25, PHLDB1, RP11-161M6.2, HEATR3, RTEL1-TNFRSF6B, and LIME1) had multiple alternatively spliced transcripts. Our study revealed that the regulation of transcriptome by glioma risk alleles is complex, with the potential for eQTL and sQTL jointly affecting gliomagenesis in risk loci. QTLs of many loci involved multiple target genes, some of which were specific to alternative splicing. Therefore, quantitative trait loci that evaluate only total gene expression will miss many important target genes.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 19 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 21%
Student > Postgraduate 2 11%
Student > Ph. D. Student 2 11%
Student > Doctoral Student 1 5%
Student > Master 1 5%
Other 1 5%
Unknown 8 42%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 21%
Medicine and Dentistry 3 16%
Agricultural and Biological Sciences 2 11%
Computer Science 1 5%
Design 1 5%
Other 0 0%
Unknown 8 42%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 May 2021.
All research outputs
#14,554,120
of 23,308,124 outputs
Outputs from Frontiers in Genetics
#4,054
of 12,328 outputs
Outputs of similar age
#229,454
of 435,301 outputs
Outputs of similar age from Frontiers in Genetics
#151
of 503 outputs
Altmetric has tracked 23,308,124 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 12,328 research outputs from this source. They receive a mean Attention Score of 3.7. This one has gotten more attention than average, scoring higher than 62% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 435,301 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 503 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.