Human disease-associated genetic variation impacts large intergenic non-coding RNA expression.
Recently it has become clear that only a small percentage (7%) of disease-associated single nucleotide polymorphisms (SNPs) are located in protein-coding regions, while the remaining 93% are located in gene regulatory regions or in intergenic regions. Thus, the understanding of how genetic variations control the expression of non-coding RNAs (in a tissue-dependent manner) has far-reaching implications. We tested the association of SNPs with expression levels (eQTLs) of large intergenic non-coding RNAs (lincRNAs), using genome-wide gene expression and genotype data from five different tissues. We identified 112 cis-regulated lincRNAs, of which 45% could be replicated in an independent dataset. We observed that 75% of the SNPs affecting lincRNA expression (lincRNA cis-eQTLs) were specific to lincRNA alone and did not affect the expression of neighboring protein-coding genes. We show that this specific genotype-lincRNA expression correlation is tissue-dependent and that many of these lincRNA cis-eQTL SNPs are also associated with complex traits and diseases.
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Vinod
V
Kumar
Harm-Jan
HJ
Westra
Juha
J
Karjalainen
Daria V
DV
Zhernakova
Tõnu
T
Esko
Barbara
B
Hrdlickova
Rodrigo
R
Almeida
Alexandra
A
Zhernakova
Eva
E
Reinmaa
Urmo
U
Võsa
Marten H
MH
Hofker
Rudolf S N
RS
Fehrmann
Jingyuan
J
Fu
Sebo
S
Withoff
Andres
A
Metspalu
Lude
L
Franke
Cisca
C
Wijmenga
D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
D062085:RNA, Long Noncoding