title: Genetics of gene expression and its effect on disease.
abstract: 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.
authors.affiliation: deCODE genetics, 101 Reykjavik, Iceland.
authors.forename: Valur
authors.initials: V
authors.lastname: Emilsson
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Amy S
authors.initials: AS
authors.lastname: Leonardson
authors.forename: Florian
authors.initials: F
authors.lastname: Zink
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Sonia
authors.initials: S
authors.lastname: Carlson
authors.forename: Agnar
authors.initials: A
authors.lastname: Helgason
authors.forename: G Bragi
authors.initials: GB
authors.lastname: Walters
authors.forename: Steinunn
authors.initials: S
authors.lastname: Gunnarsdottir
authors.forename: Magali
authors.initials: M
authors.lastname: Mouy
authors.forename: Valgerdur
authors.initials: V
authors.lastname: Steinthorsdottir
authors.forename: Gudrun H
authors.initials: GH
authors.lastname: Eiriksdottir
authors.forename: Gyda
authors.initials: G
authors.lastname: Bjornsdottir
authors.forename: Inga
authors.initials: I
authors.lastname: Reynisdottir
authors.forename: Daniel
authors.initials: D
authors.lastname: Gudbjartsson
authors.forename: Anna
authors.initials: A
authors.lastname: Helgadottir
authors.forename: Aslaug
authors.initials: A
authors.lastname: Jonasdottir
authors.forename: Adalbjorg
authors.initials: A
authors.lastname: Jonasdottir
authors.forename: Unnur
authors.initials: U
authors.lastname: Styrkarsdottir
authors.forename: Solveig
authors.initials: S
authors.lastname: Gretarsdottir
authors.forename: Kristinn P
authors.initials: KP
authors.lastname: Magnusson
authors.forename: Hreinn
authors.initials: H
authors.lastname: Stefansson
authors.forename: Ragnheidur
authors.initials: R
authors.lastname: Fossdal
authors.forename: Kristleifur
authors.initials: K
authors.lastname: Kristjansson
authors.forename: Hjortur G
authors.initials: HG
authors.lastname: Gislason
authors.forename: Tryggvi
authors.initials: T
authors.lastname: Stefansson
authors.forename: Bjorn G
authors.initials: BG
authors.lastname: Leifsson
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: John R
authors.initials: JR
authors.lastname: Lamb
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gulcher
authors.forename: Marc L
authors.initials: ML
authors.lastname: Reitman
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: Eric E
authors.initials: EE
authors.lastname: Schadt
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: 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