Conditional eQTL analysis reveals allelic heterogeneity of gene expression.
In recent years, multiple eQTL (expression quantitative trait loci) catalogs have become available that can help understand the functionality of complex trait-related single nucleotide polymorphisms (SNPs). In eQTL catalogs, gene expression is often strongly associated with multiple SNPs, which may reflect either one or multiple independent associations. Conditional eQTL analysis allows a distinction between dependent and independent eQTLs. We performed conditional eQTL analysis in 4,896 peripheral blood microarray gene expression samples. Our analysis showed that 35% of genes with a cis eQTL have at least two independent cis eQTLs; for several genes up to 13 independent cis eQTLs were identified. Also, 12% (671) of the independent cis eQTLs identified in conditional analyses were not significant in unconditional analyses. The number of GWAS catalog SNPs identified as eQTL in the conditional analyses increases with 24% as compared to unconditional analyses. We provide an online conditional cis eQTL mapping catalog for whole blood (https://eqtl.onderzoek.io/), which can be used to lookup eQTLs more accurately than in standard unconditional whole blood eQTL databases.
Department of Psychiatry, Vrije Universiteit Medical Center, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Rick
R
Jansen
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam Public Health, Amsterdam, The Netherlands.
Jouke-Jan
JJ
Hottenga
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam Public Health, Amsterdam, The Netherlands.
Michel G
MG
Nivard
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam Public Health, Amsterdam, The Netherlands.
Abdel
A
Abdellaoui
Department of Psychiatry, Vrije Universiteit Medical Center, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Bram
B
Laport
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam Public Health, Amsterdam, The Netherlands.
Eco J
EJ
de Geus
Departments of Statistics and Biological Sciences, Bioinformatics Research Center, North Carolina State University, NC, USA.
Fred A
FA
Wright
Department of Psychiatry, Vrije Universiteit Medical Center, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Brenda W J H
BWJH
Penninx
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam Public Health, Amsterdam, The Netherlands.
Dorret I
DI
Boomsma
D000483:Alleles; D001769:Blood; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018740:Genetic Heterogeneity; D055106:Genome-Wide Association Study; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics