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Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes.

Small, KS, Hedman, AK, Grundberg, E, Nica, AC, Thorleifsson, G, Kong, A, Thorsteindottir, U, Shin, SY, Richards, HB, GIANT Consortium, , MAGIC Investigators, , DIAGRAM Consortium, , Soranzo, N, Ahmadi, KR, Lindgren, CM, Stefansson, K, Dermitzakis, ET, Deloukas, P, Spector, TD, McCarthy, MI and MuTHER Consortium, (2011) Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes. Nat Genet, 43 (6). pp. 561-564.

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Abstract

Genome-wide association studies have identified many genetic variants associated with complex traits. However, at only a minority of loci have the molecular mechanisms mediating these associations been characterized. In parallel, whereas cis regulatory patterns of gene expression have been extensively explored, the identification of trans regulatory effects in humans has attracted less attention. Here we show that the type 2 diabetes and high-density lipoprotein cholesterol-associated cis-acting expression quantitative trait locus (eQTL) of the maternally expressed transcription factor KLF14 acts as a master trans regulator of adipose gene expression. Expression levels of genes regulated by this trans-eQTL are highly correlated with concurrently measured metabolic traits, and a subset of the trans-regulated genes harbor variants directly associated with metabolic phenotypes. This trans-eQTL network provides a mechanistic understanding of the effect of the KLF14 locus on metabolic disease risk and offers a potential model for other complex traits.

Item Type: Article
Authors :
NameEmailORCID
Small, KSUNSPECIFIEDUNSPECIFIED
Hedman, AKUNSPECIFIEDUNSPECIFIED
Grundberg, EUNSPECIFIEDUNSPECIFIED
Nica, ACUNSPECIFIEDUNSPECIFIED
Thorleifsson, GUNSPECIFIEDUNSPECIFIED
Kong, AUNSPECIFIEDUNSPECIFIED
Thorsteindottir, UUNSPECIFIEDUNSPECIFIED
Shin, SYUNSPECIFIEDUNSPECIFIED
Richards, HBUNSPECIFIEDUNSPECIFIED
GIANT Consortium, UNSPECIFIEDUNSPECIFIED
MAGIC Investigators, UNSPECIFIEDUNSPECIFIED
DIAGRAM Consortium, UNSPECIFIEDUNSPECIFIED
Soranzo, NUNSPECIFIEDUNSPECIFIED
Ahmadi, KRk.ahmadi@surrey.ac.ukUNSPECIFIED
Lindgren, CMUNSPECIFIEDUNSPECIFIED
Stefansson, KUNSPECIFIEDUNSPECIFIED
Dermitzakis, ETUNSPECIFIEDUNSPECIFIED
Deloukas, PUNSPECIFIEDUNSPECIFIED
Spector, TDUNSPECIFIEDUNSPECIFIED
McCarthy, MIUNSPECIFIEDUNSPECIFIED
MuTHER Consortium, UNSPECIFIEDUNSPECIFIED
Date : June 2011
Identification Number : 10.1038/ng.833
Uncontrolled Keywords : Adipose Tissue, Cholesterol, HDL, Diabetes Mellitus, Type 2, Female, Gene Expression Regulation, Genome-Wide Association Study, Genomic Imprinting, Humans, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sp Transcription Factors
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:48
Last Modified : 17 May 2017 14:45
URI: http://epubs.surrey.ac.uk/id/eprint/825180

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