1. 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:

2. Histogram of transcript-to-insulin correlations

3. Islet – enrichment for 1984 transcripts SetPvalueQvalueCountSizeTerm GOCC3.70E-060.00731922037extracellular region part GOCC3.45E-050.02941771919extracellular space GOCC4.48E-050.02942202483extracellular region GOBP8.16E-050.040237279enzyme linked receptor protein signaling pathway GOBP0.00020.076166623nervous system development GOBP0.00030.07611148neuromuscular process GOBP0.00040.076135281cell projection organization and biogenesis GOBP0.00040.076135281cell part morphogenesis GOBP0.00040.076135281cell projection morphogenesis GOMF0.00030.07613814802protein binding GOMF0.00030.076133siRNA binding GOBP0.00060.089544386cell morphogenesis GOBP0.00060.089544386cellular structure morphogenesis GOBP0.00120.146934axon choice point recognition GOBP0.00120.146934rhythmic synaptic transmission GOCC0.00110.14695367011membrane KEGG0.00130.1469617Polyunsaturated fatty acid biosynthesis GOBP0.00250.2361931021anatomical structure morphogenesis GOBP0.00290.236135retinol metabolic process GOBP0.00290.236146442cytoskeleton organization and biogenesis GOBP0.00330.2361410microtubule bundle formation GOBP0.00340.236122172transmembrane receptor protein tyrosine kinase signaling pathway GOBP0.00350.2361516regulation of catabolic process GOBP0.00360.236116111forebrain development GOBP0.00430.2361731neuromuscular process controlling balance GOBP0.00470.236122rhythmic excitation GOBP0.00470.236122protein amino acid de-ADP-ribosylation GOBP0.00470.236122ventricular cardiac muscle cell development GOBP0.00470.2361624cytokinesis

4. Islet – modules Insulin trait chromosomes 17 2 16 14 19 12 9

5. Islet – enrichment for modules chromosomes ModulePvalueQvalueCountSizeTerm BLUE0.00050.0463301068biosynthetic process 0.00060.047018511cellular lipid metabolic process 0.00090.050711241lipid biosynthetic process 0.00120.059319590lipid metabolic process GREEN0.00080.0457476phosphate transport 0.00550.0970220intermediate filament-based process 0.00560.097010707ion transport PURPLE0.00110.016572769 nucleobase, nucleoside, nucleotide and nucleic acid metabolic process BLACK0.00780.0138268sensory perception of sound MAGENTA2.54E-050.00117313cell cycle process 0.00010.00405179microtubule-based process 0.00040.00405225mitotic cell cycle 0.00050.00405228M phase 0.00060.00405239cell division 0.00090.00415266cell cycle phase 0.00110.00414162mitosis 0.00120.00414163M phase of mitotic cell cycle YELLOW0.00260.06757281cell projection organization and biogenesis 0.00260.06757281cell part morphogenesis 0.00260.06757281cell projection morphogenesis RED0.00170.0619213steroid hormone receptor signaling pathway 0.00260.06195200reproductive process BROWN0.00570.1442496response to pheromone TURQUOISE0.00020.083017279enzyme linked receptor protein signaling pathway 0.00030.083010115morphogenesis of an epithelium 0.00030.0830757morphogenesis of embryonic epithelium 0.00040.0830401021anatomical structure morphogenesis PINK0.00040.0608214vesicle organization and biogenesis 0.00920.06124384regulation of apoptosis Insulin

6. Adipose – enrichment for 605 transcripts SetPvalueQvalueCountSizeTerm GOCC4.87E-070.00051745332cytoplasm GOMF9.54E-050.05311514801catalytic activity GOBP0.00040.084611132hexose metabolic process GOBP0.00040.084611135monosaccharide metabolic process KEGG0.00030.0846412Circadian rhythm GOBP0.00060.0886417T cell selection GOBP0.00070.088615237cellular carbohydrate metabolic process GOBP0.00100.107740993intracellular signaling cascade GOBP0.00200.1790311inositol metabolic process GOBP0.00300.1790779positive regulation of signal transduction GOBP0.00380.1790427monosaccharide biosynthetic process GOBP0.00400.1790544cell redox homeostasis GOBP0.00420.1790314thymic T cell selection GOBP0.00430.1790428alcohol biosynthetic process GOBP0.00460.179024558catabolic process GOBP0.00620.1790316polyamine metabolic process GOBP0.00860.179016340carbohydrate metabolic process GOBP0.00870.1790318glucosamine metabolic process GOBP0.00870.1790318N-acetylglucosamine metabolic process GOBP0.00900.179024590lipid metabolic process GOBP0.00980.179013257alcohol metabolic process GOBP0.01210.1790679one-carbon compound metabolic process GOBP0.01300.1790438protein ubiquitination GOBP0.01340.179017388regulation of signal transduction GOBP0.01360.1790681carbohydrate biosynthetic process GOBP0.01580.179016364small GTPase mediated signal transduction GOBP0.01730.1790323amino sugar metabolic process GOBP0.01970.17907113peptidyl-amino acid modification GOBP0.02060.17907114lipid catabolic process

7. Adipose – modules Insulin trait chromosomes 19 2 9 14 17 12

8. Adipose – enrichment for modules chromosomes Insulin ModulePvalueQvalueCountSizeTerm GREEN0.0140.05604605proteolysis 0.0190.0654112nucleoside diphosphate metabolic process PINK0.0010.04304364small GTPase mediated signal transduction 0.0040.05165993intracellular signaling cascade 0.0150.0743113cellular protein complex disassembly BLACK0.0030.0366246methylation 0.0070.0436279one-carbon compound metabolic process 0.0210.0684113sulfate transport YELLOW0.0020.0173228response to hormone stimulus 0.0020.01733113peptidyl-amino acid modification 0.0070.0280256hemostasis 0.0100.0287269regulation of body fluid levels 0.0140.0327282lipid transport 0.0190.0342297glycoprotein metabolic process TURQUOISE0.0010.0713470rhythmic process 0.0020.0713212negative regulation of blood pressure 0.0020.0713344cell redox homeostasis 0.0030.071310590lipid metabolic process BLUE1.60E-060.0004417T cell selection 4.90E-050.0023314thymic T cell selection 0.00020.00397221leukocyte activation 0.00020.00547237cell activation 0.00030.0061325hexose biosynthetic process PURPLE0.00190.06523237synapse 0.00800.08693392cell junction BROWN0.00020.0234358amine biosynthetic process 0.00050.0234216polyamine metabolic process 0.00060.0234378nitrogen compound biosynthetic process 0.00090.0234221biogenic amine biosynthetic process 0.00110.0260224amino acid derivative biosynthetic process 0.00170.0346229sulfur compound biosynthetic process 0.00440.0446247detection of abiotic stimulus 0.00490.0446250inner ear morphogenesis 0.00510.0446251detection of external stimulus 0.00620.0446256ear morphogenesis 0.00690.04753187positive regulation of cell proliferation RED0.01530.0969112hydrogen peroxide metabolic process 0.02780.1410122cellular response to stimulus MAGENTA0.00300.0789279one-carbon compound metabolic process 0.01470.1436114protein targeting to membrane

9. Liver – enrichment for 485 transcripts SetPvalueQvalueCountSizeTerm GOBP0.00050.0584420nucleotide catabolic process GOBP0.00060.0584421glutathione metabolic process GOMF0.00050.05841144801catalytic activity GOMF0.00090.0584311nucleotidase activity GOBP0.00120.0658312response to dsRNA GOBP0.00160.080811205regulation of cell differentiation GOBP0.00200.0882314thymic T cell selection GOCC0.00230.09221808478intracellular GOCC0.00240.09229155microsome GOMF0.00260.0945552transferase activity, transferring alkyl or aryl (other than methyl) groups GOCC0.00280.09909159vesicular fraction GOBP0.00360.1197317T cell selection GOBP0.00440.1197436regulation of lymphocyte differentiation GOBP0.00480.1197684microtubule-based movement GOBP0.00550.1197561sulfur metabolic process GOBP0.00630.11977117bone remodeling GOBP0.00700.1197441dendrite development GOBP0.00760.1197322positive regulation of T cell differentiation GOBP0.01060.1197699cytoskeleton-dependent intracellular transport GOBP0.01090.1197325bone mineralization GOBP0.01090.1197325fat cell differentiation GOBP0.01090.1197325positive regulation of lymphocyte differentiation GOBP0.01220.1197326regulation of ossification GOBP0.01220.1197326T cell differentiation in the thymus GOBP0.01380.1197576phosphate transport GOBP0.01440.11977137tissue remodeling GOBP0.01440.11976106ossification GOBP0.01490.1197328gene silencing GOBP0.01510.11976107biomineral formation

10. Liver – modules Insulin trait chromosomes 14 9 12 17

11. Liver – enrichment for modules chromosomes Insulin ModulePvalueQvalueCountSizeTerm YELLOW0.00040.0592215lamellipodium biogenesis 0.00350.063471021anatomical structure morphogenesis 0.00500.0634252cell projection biogenesis GREEN0.01320.0868111 negative regulation of protein amino acid phosphorylation 0.01440.0882112negative regulation of phosphorylation 0.01440.0882112negative regulation of hydrolase activity RED0.00900.0128112nucleoside diphosphate metabolic process 0.01350.0177118 antigen processing and presentation of peptide antigen via MHC class I 0.01620.01862266cell cycle phase BROWN0.00050.0170214thymic T cell selection 0.00070.0189217T cell selection 0.00120.0210222positive regulation of T cell differentiation 0.00150.0210225positive regulation of lymphocyte differentiation 0.00170.0210226T cell differentiation in the thymus 0.00210.0222229regulation of T cell differentiation 0.00320.0310236regulation of lymphocyte differentiation 0.00670.0313253positive regulation of T cell activation 0.00770.03134340regulation of cell proliferation TURQUOISE0.00200.0648484microtubule-based movement 0.00200.0648340protein polymerization 0.00220.0648341dendrite development 0.00250.0648212neuron recognition 0.00250.0648212response to dsRNA 0.00290.0648345protein modification by small protein conjugation 0.00360.0648499cytoskeleton-dependent intracellular transport 0.00620.06488436response to chemical stimulus BLUE0.00540.0730221glutathione metabolic process 0.00760.0764225fat cell differentiation 0.00820.0764226regulation of ossification 0.01020.07645250gamete generation 0.01090.07644164chromatin modification 0.01150.0764231regulation of bone remodeling 0.01230.0764232regulation of tissue remodeling 0.01580.07643100response to bacterium

12. Gastroc – enrichment for 404 transcripts SetPvalueQvalueCountSizeTerm GOBP0.00030.1718421response to toxin GOBP0.00120.1718314regulation of I-kappaB kinase/NF-kappaB cascade GOMF0.00120.1718549lipid transporter activity GOBP0.00190.174828993intracellular signaling cascade GOBP0.00470.1748683246regulation of cellular process GOBP0.00650.17481125957primary metabolic process GOBP0.00750.17481125980cellular metabolic process GOBP0.00800.1748713492regulation of biological process GOBP0.00890.1748452antigen processing and presentation GOBP0.00930.1748773869biological regulation GOBP0.00940.1748582lipid transport GOBP0.01230.1748211response to metal ion GOBP0.01230.1748211positive regulation of I-kappaB kinase/NF-kappaB cascade GOBP0.01250.1748331neural crest cell development GOBP0.01250.1748331neural crest cell differentiation GOBP0.01340.174815503cell proliferation GOBP0.01480.1748333antigen processing and presentation of peptide antigen GOBP0.01550.1748461regulation of protein amino acid phosphorylation GOBP0.01570.17481196550metabolic process GOBP0.01630.1748462regulation of MAP kinase activity GOBP0.01720.1748213embryonic forelimb morphogenesis GOBP0.01740.1748335I-kappaB kinase/NF-kappaB cascade GOBP0.01780.174821815positive regulation of cellular process GOBP0.01810.17487170heart development GOBP0.01910.1748763923biopolymer metabolic process GOBP0.01980.1748214tricarboxylic acid cycle intermediate metabolic process GOBP0.01980.1748214response to inorganic substance GOBP0.01980.1748214dicarboxylic acid metabolic process GOBP0.01990.174812388regulation of signal transduction

13. Gastroc – modules Insulin trait chromosomes 14 2 12 16 19 17 9

14. Gastroc – enrichment for modules chromosomes Insulin ModulePvalueQvalueCountSizeTerm GREEN0.01570.1870115vacuolar transport 0.01570.1870115lamellipodium biogenesis 0.01670.1870116activated T cell proliferation YELLOW0.01750.0472113regulation of protein polymerization 0.01770.0472135957primary metabolic process 0.01830.0472135980cellular metabolic process 0.01880.04722157 regulation of small GTPase mediated signal transduction BLUE0.00880.0231133869biological regulation 0.01020.0231285positive regulation of protein kinase activity 0.01140.0231290positive regulation of kinase activity 0.01160.0231291positive regulation of transferase activity 0.01610.02312108negative regulation of signal transduction 0.01800.0231113246regulation of cellular process RED0.01880.1749112response to osmotic stress 0.02660.1930117gluconeogenesis 0.02810.1930118 antigen processing and presentation of peptide antigen via MHC class I BLACK0.00580.0137111 positive regulation of I-kappaB kinase/NF- kappaB cascade 0.00740.0137114heart looping 0.00740.0137114 regulation of I-kappaB kinase/NF-kappaB cascade TURQUOISE0.00130.0692171294post-translational protein modification 0.00180.0692363923biopolymer metabolic process 0.00240.0692181488protein modification process 0.00320.0692181525biopolymer modification BROWN0.00030.0105211response to metal ion 0.00060.0151214response to inorganic substance 0.00070.0159216 antigen processing and presentation of peptide antigen via MHC class II 0.00070.0159216 antigen processing and presentation of exogenous peptide antigen via MHC class II 0.00080.0163217 antigen processing and presentation of peptide or polysaccharide antigen via MHC class II 0.00090.0168218 antigen processing and presentation of exogenous peptide antigen 0.00130.0212221response to toxin 0.00160.0226223 antigen processing and presentation of exogenous antigen PINK0.00160.0153282hormone metabolic process 0.00830.0163111sequestering of lipid 0.00900.0173112negative regulation of hydrolase activity 0.00970.0176113proximal/distal pattern formation 0.00970.0176113embryonic forelimb morphogenesis

15. 4 tissues combined – modules Insulin trait Insulin