Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MuTHER Expression

ABSTRACT: Sequence-based variation in gene expression is a key driver of disease risk. Common variants regulating expression in cis have been mapped in many eQTL studies typically in single tissues from unrelated individuals. Here, we present a comprehensive analysis of gene expression across multiple tissues conducted in a large set of female individuals that allows systematic dissection of genetic and non-genetic effects on gene expression. Gene expression was quantified in subcutaneous fat, skin and LCLs derived from 856 TwinsUK participants using Illumina whole genome expression array (HumanHT-12 version 3

ORGANISM(S): Homo sapiens

SUBMITTER: Kerrin Small

PROVIDER: E-TABM-1140 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Mapping cis- and trans-regulatory effects across multiple tissues in twins.

Grundberg Elin E Small Kerrin S KS Hedman Åsa K ÅK Nica Alexandra C AC Buil Alfonso A Keildson Sarah S Bell Jordana T JT Yang Tsun-Po TP Meduri Eshwar E Barrett Amy A Nisbett James J Sekowska Magdalena M Wilk Alicja A Shin So-Youn SY Glass Daniel D Travers Mary M Min Josine L JL Ring Sue S Ho Karen K Thorleifsson Gudmar G Kong Augustine A Thorsteindottir Unnur U Ainali Chrysanthi C Dimas Antigone S AS Hassanali Neelam N Ingle Catherine C Knowles David D Krestyaninova Maria M Lowe Christopher E CE Di Meglio Paola P Montgomery Stephen B SB Parts Leopold L Potter Simon S Surdulescu Gabriela G Tsaprouni Loukia L Tsoka Sophia S Bataille Veronique V Durbin Richard R Nestle Frank O FO O'Rahilly Stephen S Soranzo Nicole N Lindgren Cecilia M CM Zondervan Krina T KT Ahmadi Kourosh R KR Schadt Eric E EE Stefansson Kari K Smith George Davey GD McCarthy Mark I MI Deloukas Panos P Dermitzakis Emmanouil T ET Spector Tim D TD

Nature genetics 20120902 10

Sequence-based variation in gene expression is a key driver of disease risk. Common variants regulating expression in cis have been mapped in many expression quantitative trait locus (eQTL) studies, typically in single tissues from unrelated individuals. Here, we present a comprehensive analysis of gene expression across multiple tissues conducted in a large set of mono- and dizygotic twins that allows systematic dissection of genetic (cis and trans) and non-genetic effects on gene expression. U ...[more]

PMID: 22941192

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Project description:The expression level for 15 887 transcripts in lymphoblastoid cell lines from 19 monozygotic twin pairs (10 male, 9 female) were analysed for the effects of genotype and sex. On an average, the effect of twin pairs explained 31% of the variance in normalized gene expression levels, consistent with previous broad sense heritability estimates. The effect of sex on gene expression levels was most noticeable on the X chromosome, which contained 15 of the 20 significantly differentially expressed genes. A high concordance was observed between the sex difference test statistics and surveys of genes escaping X chromosome inactivation. Notably, several autosomal genes showed significant differences in gene expression between the sexes despite much of the cellular environment differences being effectively removed in the cell lines. A publicly available gene expression data set from the CEPH families was used to validate the results. The heritability of gene expression levels as estimated from the two data sets showed a highly significant positive correlation, particularly when both estimates were close to one and thus had the smallest standard error. There was a large concordance between the genes significantly differentially expressed between the sexes in the two data sets. Analysis of the variability of probe binding intensities within a probe set indicated that results are robust to the possible presence of polymorphisms in the target sequences. Keywords: Monozygotic twin pair Expression Profiles Genome-wide gene expression in lymphoblastoid cell lines was determined using microarrays derived from 15 monozygotic (MZ) twin pairs (10 male, 9 female). 10 twin pair are discordant, 4 are concordant for a disease phenotype and their are 5 controls which have no disease phenotype. This data set was analyzed to interrupt replicated effects of sex and genotype, not disease characteristics. Subsets of these samples have been analyzed separately for disease characteristics, (GSE7036 M-bM-^@M-^S 3 MZ twins discordant for bipolar disorder) and (GSE7486 - 5 discordant and 4 concordant MZ twin pairs with idiopathic absence epilepsies and 5 unaffected MZ twin pairs).

Dataset Information

MuTHER Expression

Publications

Mapping cis- and trans-regulatory effects across multiple tissues in twins.

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