Weighted models for insulin Detected by scanone Detected by Ping’s multiQTL model tissue# transcripts Islet1984 Adipose605 Liver485 Gastroc404 # transcripts that match weighted insulin model in each of 4 tissues:

Histogram of transcript-to-insulin correlations

Islet – enrichment for 1984 transcripts SetPvalueQvalueCountSizeTerm GOCC3.70E extracellular region part GOCC3.45E extracellular space GOCC4.48E extracellular region GOBP8.16E enzyme linked receptor protein signaling pathway GOBP nervous system development GOBP neuromuscular process GOBP cell projection organization and biogenesis GOBP cell part morphogenesis GOBP cell projection morphogenesis GOMF protein binding GOMF siRNA binding GOBP cell morphogenesis GOBP cellular structure morphogenesis GOBP axon choice point recognition GOBP rhythmic synaptic transmission GOCC membrane KEGG Polyunsaturated fatty acid biosynthesis GOBP anatomical structure morphogenesis GOBP retinol metabolic process GOBP cytoskeleton organization and biogenesis GOBP microtubule bundle formation GOBP transmembrane receptor protein tyrosine kinase signaling pathway GOBP regulation of catabolic process GOBP forebrain development GOBP neuromuscular process controlling balance GOBP rhythmic excitation GOBP protein amino acid de-ADP-ribosylation GOBP ventricular cardiac muscle cell development GOBP cytokinesis

Islet – modules Insulin trait chromosomes

Islet – enrichment for modules chromosomes ModulePvalueQvalueCountSizeTerm BLUE biosynthetic process cellular lipid metabolic process lipid biosynthetic process lipid metabolic process GREEN phosphate transport intermediate filament-based process ion transport PURPLE nucleobase, nucleoside, nucleotide and nucleic acid metabolic process BLACK sensory perception of sound MAGENTA2.54E cell cycle process microtubule-based process mitotic cell cycle M phase cell division cell cycle phase mitosis M phase of mitotic cell cycle YELLOW cell projection organization and biogenesis cell part morphogenesis cell projection morphogenesis RED steroid hormone receptor signaling pathway reproductive process BROWN response to pheromone TURQUOISE enzyme linked receptor protein signaling pathway morphogenesis of an epithelium morphogenesis of embryonic epithelium anatomical structure morphogenesis PINK vesicle organization and biogenesis regulation of apoptosis Insulin

Adipose – enrichment for 605 transcripts SetPvalueQvalueCountSizeTerm GOCC4.87E cytoplasm GOMF9.54E catalytic activity GOBP hexose metabolic process GOBP monosaccharide metabolic process KEGG Circadian rhythm GOBP T cell selection GOBP cellular carbohydrate metabolic process GOBP intracellular signaling cascade GOBP inositol metabolic process GOBP positive regulation of signal transduction GOBP monosaccharide biosynthetic process GOBP cell redox homeostasis GOBP thymic T cell selection GOBP alcohol biosynthetic process GOBP catabolic process GOBP polyamine metabolic process GOBP carbohydrate metabolic process GOBP glucosamine metabolic process GOBP N-acetylglucosamine metabolic process GOBP lipid metabolic process GOBP alcohol metabolic process GOBP one-carbon compound metabolic process GOBP protein ubiquitination GOBP regulation of signal transduction GOBP carbohydrate biosynthetic process GOBP small GTPase mediated signal transduction GOBP amino sugar metabolic process GOBP peptidyl-amino acid modification GOBP lipid catabolic process

Adipose – modules Insulin trait chromosomes

Adipose – enrichment for modules chromosomes Insulin ModulePvalueQvalueCountSizeTerm GREEN proteolysis nucleoside diphosphate metabolic process PINK small GTPase mediated signal transduction intracellular signaling cascade cellular protein complex disassembly BLACK methylation one-carbon compound metabolic process sulfate transport YELLOW response to hormone stimulus peptidyl-amino acid modification hemostasis regulation of body fluid levels lipid transport glycoprotein metabolic process TURQUOISE rhythmic process negative regulation of blood pressure cell redox homeostasis lipid metabolic process BLUE1.60E T cell selection 4.90E thymic T cell selection leukocyte activation cell activation hexose biosynthetic process PURPLE synapse cell junction BROWN amine biosynthetic process polyamine metabolic process nitrogen compound biosynthetic process biogenic amine biosynthetic process amino acid derivative biosynthetic process sulfur compound biosynthetic process detection of abiotic stimulus inner ear morphogenesis detection of external stimulus ear morphogenesis positive regulation of cell proliferation RED hydrogen peroxide metabolic process cellular response to stimulus MAGENTA one-carbon compound metabolic process protein targeting to membrane

Liver – enrichment for 485 transcripts SetPvalueQvalueCountSizeTerm GOBP nucleotide catabolic process GOBP glutathione metabolic process GOMF catalytic activity GOMF nucleotidase activity GOBP response to dsRNA GOBP regulation of cell differentiation GOBP thymic T cell selection GOCC intracellular GOCC microsome GOMF transferase activity, transferring alkyl or aryl (other than methyl) groups GOCC vesicular fraction GOBP T cell selection GOBP regulation of lymphocyte differentiation GOBP microtubule-based movement GOBP sulfur metabolic process GOBP bone remodeling GOBP dendrite development GOBP positive regulation of T cell differentiation GOBP cytoskeleton-dependent intracellular transport GOBP bone mineralization GOBP fat cell differentiation GOBP positive regulation of lymphocyte differentiation GOBP regulation of ossification GOBP T cell differentiation in the thymus GOBP phosphate transport GOBP tissue remodeling GOBP ossification GOBP gene silencing GOBP biomineral formation

Liver – modules Insulin trait chromosomes

Liver – enrichment for modules chromosomes Insulin ModulePvalueQvalueCountSizeTerm YELLOW lamellipodium biogenesis anatomical structure morphogenesis cell projection biogenesis GREEN negative regulation of protein amino acid phosphorylation negative regulation of phosphorylation negative regulation of hydrolase activity RED nucleoside diphosphate metabolic process antigen processing and presentation of peptide antigen via MHC class I cell cycle phase BROWN thymic T cell selection T cell selection positive regulation of T cell differentiation positive regulation of lymphocyte differentiation T cell differentiation in the thymus regulation of T cell differentiation regulation of lymphocyte differentiation positive regulation of T cell activation regulation of cell proliferation TURQUOISE microtubule-based movement protein polymerization dendrite development neuron recognition response to dsRNA protein modification by small protein conjugation cytoskeleton-dependent intracellular transport response to chemical stimulus BLUE glutathione metabolic process fat cell differentiation regulation of ossification gamete generation chromatin modification regulation of bone remodeling regulation of tissue remodeling response to bacterium

Gastroc – enrichment for 404 transcripts SetPvalueQvalueCountSizeTerm GOBP response to toxin GOBP regulation of I-kappaB kinase/NF-kappaB cascade GOMF lipid transporter activity GOBP intracellular signaling cascade GOBP regulation of cellular process GOBP primary metabolic process GOBP cellular metabolic process GOBP regulation of biological process GOBP antigen processing and presentation GOBP biological regulation GOBP lipid transport GOBP response to metal ion GOBP positive regulation of I-kappaB kinase/NF-kappaB cascade GOBP neural crest cell development GOBP neural crest cell differentiation GOBP cell proliferation GOBP antigen processing and presentation of peptide antigen GOBP regulation of protein amino acid phosphorylation GOBP metabolic process GOBP regulation of MAP kinase activity GOBP embryonic forelimb morphogenesis GOBP I-kappaB kinase/NF-kappaB cascade GOBP positive regulation of cellular process GOBP heart development GOBP biopolymer metabolic process GOBP tricarboxylic acid cycle intermediate metabolic process GOBP response to inorganic substance GOBP dicarboxylic acid metabolic process GOBP regulation of signal transduction

Gastroc – modules Insulin trait chromosomes

Gastroc – enrichment for modules chromosomes Insulin ModulePvalueQvalueCountSizeTerm GREEN vacuolar transport lamellipodium biogenesis activated T cell proliferation YELLOW regulation of protein polymerization primary metabolic process cellular metabolic process regulation of small GTPase mediated signal transduction BLUE biological regulation positive regulation of protein kinase activity positive regulation of kinase activity positive regulation of transferase activity negative regulation of signal transduction regulation of cellular process RED response to osmotic stress gluconeogenesis antigen processing and presentation of peptide antigen via MHC class I BLACK positive regulation of I-kappaB kinase/NF- kappaB cascade heart looping regulation of I-kappaB kinase/NF-kappaB cascade TURQUOISE post-translational protein modification biopolymer metabolic process protein modification process biopolymer modification BROWN response to metal ion response to inorganic substance antigen processing and presentation of peptide antigen via MHC class II antigen processing and presentation of exogenous peptide antigen via MHC class II antigen processing and presentation of peptide or polysaccharide antigen via MHC class II antigen processing and presentation of exogenous peptide antigen response to toxin antigen processing and presentation of exogenous antigen PINK hormone metabolic process sequestering of lipid negative regulation of hydrolase activity proximal/distal pattern formation embryonic forelimb morphogenesis

4 tissues combined – modules Insulin trait Insulin