A Systems Genetics Approach Identified GPD1L and its Molecular Mechanism for Obesity in Human Adipose Tissue.

Scientific Reports
Hao HeHong-Wen Deng

Abstract

To explore novel molecular mechanisms underlying obesity, we applied a systems genetics framework to integrate risk genetic loci from the largest body mass index (BMI) genome-wide association studies (GWAS) meta-analysis with mRNA and microRNA profiling in adipose tissue from 200 subjects. One module was identified to be most significantly associated with obesity and other metabolic traits. We identified eight hub genes which likely play important roles in obesity metabolism and identified microRNAs that significantly negatively correlated with hub genes. This module was preserved in other three test gene expression datasets, and all hub genes were consistently downregulated in obese subjects through the meta-analysis. Gene GPD1L had the highest connectivity and was identified a key causal regulator in the module. Gene GPD1L was significantly negatively correlated with the expression of miR-210, which was experimentally validated that miR-210 regulated GPD1L protein level through direct interaction with its mRNA three prime untranslated region (3'-UTR). GPD1L was found to be upregulated during weight loss and weight maintenance induced by low calorie diet (LCD), while downregulated during weight gain induced by high-fat diet (H...Continue Reading

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Datasets Mentioned

BETA
GSE32512
GSE64567
E-MTAB-54
GSE60946
GSE25910

Methods Mentioned

BETA
biopsies
PCA
PCR
electrophoresis

Clinical Trials Mentioned

NCT00072995

Software Mentioned

Affy package
WGCNA R package
miRComb
WGCNA
Linear Models for Microarray Analysis ( LIMMA )
LIMMA
Affymetrix Expression Console
impute
MGI
MicroCosm

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