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PLoS One. 2019 Jun 17;14(6):e0217765. doi: 10.1371/journal.pone.0217765. eCollection 2019.

Comparison of quantitative trait loci methods: Total expression and allelic imbalance method in brain RNA-seq.

Author information

Cardiovascular Medicine Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Karolinska University Hospital, Solna, Sweden.
Roskilde Hospital, Roskilde, Denmark.
Lieber Institute for Brain Development, Baltimore, United States of America.
Lundbeck A/S, Valby, Denmark.
Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.



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.


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).


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.


Our results suggest that the aeQTL strategy complements the eQTL approach to susceptibility gene identification.

Conflict of interest statement

A consortium comprising The Lieber Institute for Brain Development, Pfizer, Lilly, Roche, Astra Zeneca, Astellas and Lundbeck paid for the material in the study. However, these companies had no influence over the conclusions of the study. The funding from Lundbeck A/S does not alter our adherence to PLOS ONE policies on sharing data and materials.

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