Genetics of gene expression and its effect on disease.
Common human diseases result from the interplay of many genes and environmental factors. Therefore, a more integrative biology approach is needed to unravel the complexity and causes of such diseases. To elucidate the complexity of common human diseases such as obesity, we have analysed the expression of 23,720 transcripts in large population-based blood and adipose tissue cohorts comprehensively assessed for various phenotypes, including traits related to clinical obesity. In contrast to the blood expression profiles, we observed a marked correlation between gene expression in adipose tissue and obesity-related traits. Genome-wide linkage and association mapping revealed a highly significant genetic component to gene expression traits, including a strong genetic effect of proximal (cis) signals, with 50% of the cis signals overlapping between the two tissues profiled. Here we demonstrate an extensive transcriptional network constructed from the human adipose data that exhibits significant overlap with similar network modules constructed from mouse adipose data. A core network module in humans and mice was identified that is enriched for genes involved in the inflammatory and immune response and has been found to be causally associated to obesity-related traits.
Emilsson
Valur
V
deCODE genetics, 101 Reykjavik, Iceland.
Thorleifsson
Gudmar
G
Zhang
Bin
B
Leonardson
Amy S
AS
Zink
Florian
F
Zhu
Jun
J
Carlson
Sonia
S
Helgason
Agnar
A
Walters
G Bragi
GB
Gunnarsdottir
Steinunn
S
Mouy
Magali
M
Steinthorsdottir
Valgerdur
V
Eiriksdottir
Gudrun H
GH
Bjornsdottir
Gyda
G
Reynisdottir
Inga
I
Gudbjartsson
Daniel
D
Helgadottir
Anna
A
Jonasdottir
Aslaug
A
Jonasdottir
Adalbjorg
A
Styrkarsdottir
Unnur
U
Gretarsdottir
Solveig
S
Magnusson
Kristinn P
KP
Stefansson
Hreinn
H
Fossdal
Ragnheidur
R
Kristjansson
Kristleifur
K
Gislason
Hjortur G
HG
Stefansson
Tryggvi
T
Leifsson
Bjorn G
BG
Thorsteinsdottir
Unnur
U
Lamb
John R
JR
Gulcher
Jeffrey R
JR
Reitman
Marc L
ML
Kong
Augustine
A
Schadt
Eric E
EE
Stefansson
Kari
K
D000273:Adipose Tissue / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001769:Blood / Q000378:metabolism; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D007055:Iceland; D008126:Lod Score; D008297:Male; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D018401:Sample Size; D049629:Waist-Hip Ratio; D044465:White People / Q000235:genetics