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Series GSE48152 Query DataSets for GSE48152
Status Public on Jun 21, 2013
Title Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association.
Organism Homo sapiens
Experiment type Expression profiling by array
Summary The identification of multiple signals at individual loci could explain additional phenotypic variance ('missing heritability') of common traits, and help identify causal genes. We examined gene expression levels as a model trait because of the large number of strong genetic effects acting in cis. Using expression profiles from 613 individuals, we performed genome-wide single nucleotide polymorphism (SNP) analyses to identify cis-expression quantitative trait loci (eQTLs), and conditional analysis to identify second signals. We examined patterns of association when accounting for multiple SNPs at a locus and when including additional SNPs from the 1000 Genomes Project. We identified 1298 cis-eQTLs at an approximate false discovery rate 0.01, of which 118 (9%) showed evidence of a second independent signal. For this subset of 118 traits, accounting for two signals resulted in an average 31% increase in phenotypic variance explained (Wilcoxon P< 0.0001). The association of SNPs with cis gene expression could increase, stay similar or decrease in significance when accounting for linkage disequilibrium with second signals at the same locus. Pairs of SNPs increasing in significance tended to have gene expression increasing alleles on opposite haplotypes, whereas pairs of SNPs decreasing in significance tended to have gene expression increasing alleles on the same haplotypes. Adding data from the 1000 Genomes Project showed that apparently independent signals could be potentially explained by a single association signal. Our results show that accounting for multiple variants at a locus will increase the variance explained in a substantial fraction of loci, but that allelic heterogeneity will be difficult to define without resequencing loci and functional work.
 
Overall design Gene expression data was determined of peripheral blood samples (n=705) from InChianti cohort.
 
Citation(s) 21798870, 21668623, 24013639, 27625022
Submission date Jun 20, 2013
Last update date Aug 16, 2018
Contact name Hanieh Yaghootkar
E-mail(s) [email protected]
Organization name University of Exeter Medical School
Department Genetics
Lab Genetics of Complex Traits
Street address Magdalen Road
City Exeter
ZIP/Postal code EX1 2LU
Country United Kingdom
 
Platforms (1)
GPL6947 Illumina HumanHT-12 V3.0 expression beadchip
Samples (705)
GSM1170040 Peripheral blood RNA from InChianti sample 1
GSM1170041 Peripheral blood RNA from InChianti sample 2
GSM1170042 Peripheral blood RNA from InChianti sample 3
Relations
BioProject PRJNA209050

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE48152_RAW.tar 6.2 Mb (http)(custom) TAR
GSE48152_RAW.txt.gz 228.5 Mb (ftp)(http) TXT
Processed data included within Sample table

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