TY - JOUR
T1 - Coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes
AU - Min, Josine L
AU - Nicholson, George
AU - Halgrimsdottir, Ingileif
AU - Almstrup, Kristian
AU - Petri, Andreas
AU - Barrett, Amy
AU - Travers, Mary
AU - Rayner, Nigel W
AU - Mägi, Reedik
AU - Pettersson, Fredrik H
AU - Broxholme, John
AU - Neville, Matt J
AU - Wills, Quin F
AU - Cheeseman, Jane
AU - Allen, Maxine
AU - Holmes, Chris C
AU - Spector, Tim D
AU - Fleckner, Jan
AU - McCarthy, Mark I
AU - Karpe, Fredrik
AU - Lindgren, Cecilia M
AU - Zondervan, Krina T
AU - GIANT Consortium
PY - 2012
Y1 - 2012
N2 - Metabolic Syndrome (MetS) is highly prevalent and has considerable public health impact, but its underlying genetic factors remain elusive. To identify gene networks involved in MetS, we conducted whole-genome expression and genotype profiling on abdominal (ABD) and gluteal (GLU) adipose tissue, and whole blood (WB), from 29 MetS cases and 44 controls. Co-expression network analysis for each tissue independently identified nine, six, and zero MetS-associated modules of coexpressed genes in ABD, GLU, and WB, respectively. Of 8,992 probesets expressed in ABD or GLU, 685 (7.6%) were expressed in ABD and 51 (0.6%) in GLU only. Differential eigengene network analysis of 8,256 shared probesets detected 22 shared modules with high preservation across adipose depots (D(ABD-GLU) = 0.89), seven of which were associated with MetS (FDR P100,000 individuals; rs10282458, affecting expression of RARRES2 (encoding chemerin), was associated with body mass index (BMI) (P = 6.0×10(-4)); and rs2395185, affecting inter-depot differences of HLA-DRB1 expression, was associated with high-density lipoprotein (P = 8.7×10(-4)) and BMI-adjusted waist-to-hip ratio (P = 2.4×10(-4)). Since many genes and their interactions influence complex traits such as MetS, integrated analysis of genotypes and coexpression networks across multiple tissues relevant to clinical traits is an efficient strategy to identify novel associations.
AB - Metabolic Syndrome (MetS) is highly prevalent and has considerable public health impact, but its underlying genetic factors remain elusive. To identify gene networks involved in MetS, we conducted whole-genome expression and genotype profiling on abdominal (ABD) and gluteal (GLU) adipose tissue, and whole blood (WB), from 29 MetS cases and 44 controls. Co-expression network analysis for each tissue independently identified nine, six, and zero MetS-associated modules of coexpressed genes in ABD, GLU, and WB, respectively. Of 8,992 probesets expressed in ABD or GLU, 685 (7.6%) were expressed in ABD and 51 (0.6%) in GLU only. Differential eigengene network analysis of 8,256 shared probesets detected 22 shared modules with high preservation across adipose depots (D(ABD-GLU) = 0.89), seven of which were associated with MetS (FDR P100,000 individuals; rs10282458, affecting expression of RARRES2 (encoding chemerin), was associated with body mass index (BMI) (P = 6.0×10(-4)); and rs2395185, affecting inter-depot differences of HLA-DRB1 expression, was associated with high-density lipoprotein (P = 8.7×10(-4)) and BMI-adjusted waist-to-hip ratio (P = 2.4×10(-4)). Since many genes and their interactions influence complex traits such as MetS, integrated analysis of genotypes and coexpression networks across multiple tissues relevant to clinical traits is an efficient strategy to identify novel associations.
U2 - 10.1371/journal.pgen.1002505
DO - 10.1371/journal.pgen.1002505
M3 - Journal article
C2 - 22383892
SN - 1553-7390
VL - 8
SP - e1002505
JO - P L o S Genetics
JF - P L o S Genetics
IS - 2
ER -