Comparison of quantitative trait loci methods: Total expression and allelic imbalance method in brain RNA-seq
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Comparison of quantitative trait loci methods : Total expression and allelic imbalance method in brain RNA-seq. / Gådin, Jesper R; Buil, Alfonso; Colantuoni, Carlo; Jaffe, Andrew E; Nielsen, Jacob; Shin, Joo-Heon; Hyde, Thomas M; Kleinman, Joel E; Plath, Niels; Eriksson, Per; Brunak, Søren; Didriksen, Michael; Weinberger, Daniel R; Folkersen, Lasse; BrainSeq Consortium.
In: PLoS ONE, Vol. 14, No. 6, e0217765, 2019.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Comparison of quantitative trait loci methods
T2 - Total expression and allelic imbalance method in brain RNA-seq
AU - Gådin, Jesper R
AU - Buil, Alfonso
AU - Colantuoni, Carlo
AU - Jaffe, Andrew E
AU - Nielsen, Jacob
AU - Shin, Joo-Heon
AU - Hyde, Thomas M
AU - Kleinman, Joel E
AU - Plath, Niels
AU - Eriksson, Per
AU - Brunak, Søren
AU - Didriksen, Michael
AU - Weinberger, Daniel R
AU - Folkersen, Lasse
AU - BrainSeq Consortium
PY - 2019
Y1 - 2019
N2 - BACKGROUND: Of the 108 Schizophrenia (SZ) risk-loci discovered through genome-wide association studies (GWAS), 96 are not altering the sequence of any protein. Evidence linking non-coding risk-SNPs and genes may be established using expression quantitative trait loci (eQTL). However, other approaches such allelic expression quantitative trait loci (aeQTL) also may be of use.METHODS: We applied both the eQTL and aeQTL analysis to a biobank of deeply sequenced RNA from 680 dorso-lateral pre-frontal cortex (DLPFC) samples. For each of 340 genes proximal to the SZ risk-SNPs, we asked how much SNP-genotype affected total expression (eQTL), as well as how much the expression ratio between the two alleles differed from 1:1 as a consequence of the risk-SNP genotype (aeQTL).RESULTS: We analyzed overlap with comparable eQTL-findings: 16 of the 30 risk-SNPs known to have gene-level eQTL also had gene-level aeQTL effects. 6 of 21 risk-SNPs with known splice-eQTL had exon-aeQTL effects. 12 novel potential risk genes were identified with the aeQTL approach, while 55 tested SNP-pairs were found as eQTL but not aeQTL. Of the tested 108 loci we could find at least one gene to be associated with 21 of the risk-SNPs using gene-level aeQTL, and with an additional 18 risk-SNPs using exon-level aeQTL.CONCLUSION: Our results suggest that the aeQTL strategy complements the eQTL approach to susceptibility gene identification.
AB - BACKGROUND: Of the 108 Schizophrenia (SZ) risk-loci discovered through genome-wide association studies (GWAS), 96 are not altering the sequence of any protein. Evidence linking non-coding risk-SNPs and genes may be established using expression quantitative trait loci (eQTL). However, other approaches such allelic expression quantitative trait loci (aeQTL) also may be of use.METHODS: We applied both the eQTL and aeQTL analysis to a biobank of deeply sequenced RNA from 680 dorso-lateral pre-frontal cortex (DLPFC) samples. For each of 340 genes proximal to the SZ risk-SNPs, we asked how much SNP-genotype affected total expression (eQTL), as well as how much the expression ratio between the two alleles differed from 1:1 as a consequence of the risk-SNP genotype (aeQTL).RESULTS: We analyzed overlap with comparable eQTL-findings: 16 of the 30 risk-SNPs known to have gene-level eQTL also had gene-level aeQTL effects. 6 of 21 risk-SNPs with known splice-eQTL had exon-aeQTL effects. 12 novel potential risk genes were identified with the aeQTL approach, while 55 tested SNP-pairs were found as eQTL but not aeQTL. Of the tested 108 loci we could find at least one gene to be associated with 21 of the risk-SNPs using gene-level aeQTL, and with an additional 18 risk-SNPs using exon-level aeQTL.CONCLUSION: Our results suggest that the aeQTL strategy complements the eQTL approach to susceptibility gene identification.
U2 - 10.1371/journal.pone.0217765
DO - 10.1371/journal.pone.0217765
M3 - Journal article
C2 - 31206532
VL - 14
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 6
M1 - e0217765
ER -
ID: 222692695