[HTML][HTML] Identification of an imprinted master trans-regulator at the KLF14 locus related to multiple metabolic phenotypes

KS Small, ÅK Hedman, E Grundberg, AC Nica… - Nature …, 2011 - ncbi.nlm.nih.gov
KS Small, ÅK Hedman, E Grundberg, AC Nica, G Thorleifsson, A Kong, U Thorsteindottir…
Nature genetics, 2011ncbi.nlm.nih.gov
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, whilst cis-regulatory patterns of gene
expression have been extensively explored, the identification of trans-regulatory effects in
humans has attracted less attention. We demonstrate that the Type 2 diabetes and HDL-
cholesterol associated cis-acting eQTL of the maternally-expressed transcription factor …
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, whilst cis-regulatory patterns of gene expression have been extensively explored, the identification of trans-regulatory effects in humans has attracted less attention. We demonstrate that the Type 2 diabetes and HDL-cholesterol associated cis-acting 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-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, providing a potential model for other complex traits.
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