Weighted models for insulinDetected by scanone

Detected by Ping’s multiQTL model

tissue # transcripts

Islet 1984

Adipose 605

Liver 485

Gastroc 404

# transcripts that matchweighted insulin modelin each of 4 tissues:

Histogram of transcript-to-insulin correlations

Islet – enrichment for 1984 transcripts

Set Pvalue Qvalue Count Size TermGOCC 3.70E-06 0.0073 192 2037 extracellular region partGOCC 3.45E-05 0.0294 177 1919 extracellular spaceGOCC 4.48E-05 0.0294 220 2483 extracellular regionGOBP 8.16E-05 0.0402 37 279 enzyme linked receptor protein signaling pathwayGOBP 0.0002 0.0761 66 623 nervous system developmentGOBP 0.0003 0.0761 11 48 neuromuscular processGOBP 0.0004 0.0761 35 281 cell projection organization and biogenesisGOBP 0.0004 0.0761 35 281 cell part morphogenesisGOBP 0.0004 0.0761 35 281 cell projection morphogenesisGOMF 0.0003 0.0761 381 4802 protein bindingGOMF 0.0003 0.0761 3 3 siRNA bindingGOBP 0.0006 0.0895 44 386 cell morphogenesisGOBP 0.0006 0.0895 44 386 cellular structure morphogenesisGOBP 0.0012 0.1469 3 4 axon choice point recognitionGOBP 0.0012 0.1469 3 4 rhythmic synaptic transmissionGOCC 0.0011 0.1469 536 7011 membraneKEGG 0.0013 0.1469 6 17 Polyunsaturated fatty acid biosynthesisGOBP 0.0025 0.2361 93 1021 anatomical structure morphogenesisGOBP 0.0029 0.2361 3 5 retinol metabolic processGOBP 0.0029 0.2361 46 442 cytoskeleton organization and biogenesisGOBP 0.0033 0.2361 4 10 microtubule bundle formationGOBP 0.0034 0.2361 22 172 transmembrane receptor protein tyrosine kinase signaling pathwayGOBP 0.0035 0.2361 5 16 regulation of catabolic processGOBP 0.0036 0.2361 16 111 forebrain developmentGOBP 0.0043 0.2361 7 31 neuromuscular process controlling balanceGOBP 0.0047 0.2361 2 2 rhythmic excitationGOBP 0.0047 0.2361 2 2 protein amino acid de-ADP-ribosylationGOBP 0.0047 0.2361 2 2 ventricular cardiac muscle cell developmentGOBP 0.0047 0.2361 6 24 cytokinesis

Islet – modules

Insulin trait

chromosomes

17

2

16

14

19

12

9

Islet – enrichment for modules

chromosomes

Module Pvalue Qvalue Count Size Term

BLUE 0.0005 0.0463 30 1068 biosynthetic process0.0006 0.0470 18 511 cellular lipid metabolic process0.0009 0.0507 11 241 lipid biosynthetic process0.0012 0.0593 19 590 lipid metabolic process

GREEN 0.0008 0.0457 4 76 phosphate transport0.0055 0.0970 2 20 intermediate filament-based process0.0056 0.0970 10 707 ion transport

PURPLE 0.0011 0.0165 7 2769nucleobase, nucleoside, nucleotide and nucleic acid metabolic process

BLACK 0.0078 0.0138 2 68 sensory perception of soundMAGENTA 2.54E-05 0.0011 7 313 cell cycle process

0.0001 0.0040 5 179 microtubule-based process0.0004 0.0040 5 225 mitotic cell cycle0.0005 0.0040 5 228 M phase0.0006 0.0040 5 239 cell division0.0009 0.0041 5 266 cell cycle phase0.0011 0.0041 4 162 mitosis0.0012 0.0041 4 163 M phase of mitotic cell cycle

YELLOW 0.0026 0.0675 7 281 cell projection organization and biogenesis0.0026 0.0675 7 281 cell part morphogenesis0.0026 0.0675 7 281 cell projection morphogenesis

RED 0.0017 0.0619 2 13 steroid hormone receptor signaling pathway0.0026 0.0619 5 200 reproductive process

BROWN 0.0057 0.1442 4 96 response to pheromoneTURQUOISE 0.0002 0.0830 17 279 enzyme linked receptor protein signaling pathway

0.0003 0.0830 10 115 morphogenesis of an epithelium0.0003 0.0830 7 57 morphogenesis of embryonic epithelium0.0004 0.0830 40 1021 anatomical structure morphogenesis

PINK 0.0004 0.0608 2 14 vesicle organization and biogenesis0.0092 0.0612 4 384 regulation of apoptosis

Insulin

Adipose – enrichment for 605 transcripts

Set Pvalue Qvalue Count Size TermGOCC 4.87E-07 0.0005 174 5332 cytoplasmGOMF 9.54E-05 0.0531 151 4801 catalytic activityGOBP 0.0004 0.0846 11 132 hexose metabolic processGOBP 0.0004 0.0846 11 135 monosaccharide metabolic processKEGG 0.0003 0.0846 4 12 Circadian rhythmGOBP 0.0006 0.0886 4 17 T cell selectionGOBP 0.0007 0.0886 15 237 cellular carbohydrate metabolic processGOBP 0.0010 0.1077 40 993 intracellular signaling cascadeGOBP 0.0020 0.1790 3 11 inositol metabolic processGOBP 0.0030 0.1790 7 79 positive regulation of signal transductionGOBP 0.0038 0.1790 4 27 monosaccharide biosynthetic processGOBP 0.0040 0.1790 5 44 cell redox homeostasisGOBP 0.0042 0.1790 3 14 thymic T cell selectionGOBP 0.0043 0.1790 4 28 alcohol biosynthetic processGOBP 0.0046 0.1790 24 558 catabolic processGOBP 0.0062 0.1790 3 16 polyamine metabolic processGOBP 0.0086 0.1790 16 340 carbohydrate metabolic processGOBP 0.0087 0.1790 3 18 glucosamine metabolic processGOBP 0.0087 0.1790 3 18 N-acetylglucosamine metabolic processGOBP 0.0090 0.1790 24 590 lipid metabolic processGOBP 0.0098 0.1790 13 257 alcohol metabolic processGOBP 0.0121 0.1790 6 79 one-carbon compound metabolic processGOBP 0.0130 0.1790 4 38 protein ubiquitinationGOBP 0.0134 0.1790 17 388 regulation of signal transductionGOBP 0.0136 0.1790 6 81 carbohydrate biosynthetic processGOBP 0.0158 0.1790 16 364 small GTPase mediated signal transductionGOBP 0.0173 0.1790 3 23 amino sugar metabolic processGOBP 0.0197 0.1790 7 113 peptidyl-amino acid modificationGOBP 0.0206 0.1790 7 114 lipid catabolic process

Adipose – modules

Insulin trait

chromosomes

19

2914

17

12

Adipose – enrichment for modules

chromosomes

Insulin

Module Pvalue Qvalue Count Size TermGREEN 0.014 0.0560 4 605 proteolysis

0.019 0.0654 1 12 nucleoside diphosphate metabolic processPINK 0.001 0.0430 4 364 small GTPase mediated signal transduction

0.004 0.0516 5 993 intracellular signaling cascade0.015 0.0743 1 13 cellular protein complex disassembly

BLACK 0.003 0.0366 2 46 methylation0.007 0.0436 2 79 one-carbon compound metabolic process0.021 0.0684 1 13 sulfate transport

YELLOW 0.002 0.0173 2 28 response to hormone stimulus0.002 0.0173 3 113 peptidyl-amino acid modification0.007 0.0280 2 56 hemostasis0.010 0.0287 2 69 regulation of body fluid levels0.014 0.0327 2 82 lipid transport0.019 0.0342 2 97 glycoprotein metabolic process

TURQUOISE 0.001 0.0713 4 70 rhythmic process0.002 0.0713 2 12 negative regulation of blood pressure0.002 0.0713 3 44 cell redox homeostasis0.003 0.0713 10 590 lipid metabolic process

BLUE 1.60E-06 0.0004 4 17 T cell selection4.90E-05 0.0023 3 14 thymic T cell selection

0.0002 0.0039 7 221 leukocyte activation0.0002 0.0054 7 237 cell activation0.0003 0.0061 3 25 hexose biosynthetic process

PURPLE 0.0019 0.0652 3 237 synapse0.0080 0.0869 3 392 cell junction

BROWN 0.0002 0.0234 3 58 amine biosynthetic process0.0005 0.0234 2 16 polyamine metabolic process0.0006 0.0234 3 78 nitrogen compound biosynthetic process0.0009 0.0234 2 21 biogenic amine biosynthetic process0.0011 0.0260 2 24 amino acid derivative biosynthetic process0.0017 0.0346 2 29 sulfur compound biosynthetic process0.0044 0.0446 2 47 detection of abiotic stimulus0.0049 0.0446 2 50 inner ear morphogenesis0.0051 0.0446 2 51 detection of external stimulus0.0062 0.0446 2 56 ear morphogenesis0.0069 0.0475 3 187 positive regulation of cell proliferation

RED 0.0153 0.0969 1 12 hydrogen peroxide metabolic process0.0278 0.1410 1 22 cellular response to stimulus

MAGENTA 0.0030 0.0789 2 79 one-carbon compound metabolic process0.0147 0.1436 1 14 protein targeting to membrane

Liver – enrichment for 485 transcripts

Set Pvalue Qvalue Count Size TermGOBP 0.0005 0.0584 4 20 nucleotide catabolic processGOBP 0.0006 0.0584 4 21 glutathione metabolic processGOMF 0.0005 0.0584 114 4801 catalytic activityGOMF 0.0009 0.0584 3 11 nucleotidase activityGOBP 0.0012 0.0658 3 12 response to dsRNAGOBP 0.0016 0.0808 11 205 regulation of cell differentiationGOBP 0.0020 0.0882 3 14 thymic T cell selectionGOCC 0.0023 0.0922 180 8478 intracellularGOCC 0.0024 0.0922 9 155 microsomeGOMF 0.0026 0.0945 5 52 transferase activity, transferring alkyl or aryl (other than methyl) groupsGOCC 0.0028 0.0990 9 159 vesicular fractionGOBP 0.0036 0.1197 3 17 T cell selectionGOBP 0.0044 0.1197 4 36 regulation of lymphocyte differentiationGOBP 0.0048 0.1197 6 84 microtubule-based movementGOBP 0.0055 0.1197 5 61 sulfur metabolic processGOBP 0.0063 0.1197 7 117 bone remodelingGOBP 0.0070 0.1197 4 41 dendrite developmentGOBP 0.0076 0.1197 3 22 positive regulation of T cell differentiationGOBP 0.0106 0.1197 6 99 cytoskeleton-dependent intracellular transportGOBP 0.0109 0.1197 3 25 bone mineralizationGOBP 0.0109 0.1197 3 25 fat cell differentiationGOBP 0.0109 0.1197 3 25 positive regulation of lymphocyte differentiationGOBP 0.0122 0.1197 3 26 regulation of ossificationGOBP 0.0122 0.1197 3 26 T cell differentiation in the thymusGOBP 0.0138 0.1197 5 76 phosphate transportGOBP 0.0144 0.1197 7 137 tissue remodelingGOBP 0.0144 0.1197 6 106 ossificationGOBP 0.0149 0.1197 3 28 gene silencingGOBP 0.0151 0.1197 6 107 biomineral formation

Liver – modules

Insulin trait

chromosomes

14

9

12

17

Liver – enrichment for modules

chromosomes

Insulin

Module Pvalue Qvalue Count Size TermYELLOW 0.0004 0.0592 2 15 lamellipodium biogenesis

0.0035 0.0634 7 1021 anatomical structure morphogenesis0.0050 0.0634 2 52 cell projection biogenesis

GREEN 0.0132 0.0868 1 11negative regulation of protein amino acid phosphorylation

0.0144 0.0882 1 12 negative regulation of phosphorylation0.0144 0.0882 1 12 negative regulation of hydrolase activity

RED 0.0090 0.0128 1 12 nucleoside diphosphate metabolic process

0.0135 0.0177 1 18antigen processing and presentation of peptide antigen via MHC class I

0.0162 0.0186 2 266 cell cycle phaseBROWN 0.0005 0.0170 2 14 thymic T cell selection

0.0007 0.0189 2 17 T cell selection0.0012 0.0210 2 22 positive regulation of T cell differentiation0.0015 0.0210 2 25 positive regulation of lymphocyte differentiation0.0017 0.0210 2 26 T cell differentiation in the thymus0.0021 0.0222 2 29 regulation of T cell differentiation0.0032 0.0310 2 36 regulation of lymphocyte differentiation0.0067 0.0313 2 53 positive regulation of T cell activation0.0077 0.0313 4 340 regulation of cell proliferation

TURQUOISE 0.0020 0.0648 4 84 microtubule-based movement0.0020 0.0648 3 40 protein polymerization0.0022 0.0648 3 41 dendrite development0.0025 0.0648 2 12 neuron recognition0.0025 0.0648 2 12 response to dsRNA0.0029 0.0648 3 45 protein modification by small protein conjugation0.0036 0.0648 4 99 cytoskeleton-dependent intracellular transport0.0062 0.0648 8 436 response to chemical stimulus

BLUE 0.0054 0.0730 2 21 glutathione metabolic process0.0076 0.0764 2 25 fat cell differentiation0.0082 0.0764 2 26 regulation of ossification0.0102 0.0764 5 250 gamete generation0.0109 0.0764 4 164 chromatin modification0.0115 0.0764 2 31 regulation of bone remodeling0.0123 0.0764 2 32 regulation of tissue remodeling0.0158 0.0764 3 100 response to bacterium

Gastroc – enrichment for 404 transcripts

Set Pvalue Qvalue Count Size TermGOBP 0.0003 0.1718 4 21 response to toxinGOBP 0.0012 0.1718 3 14 regulation of I-kappaB kinase/NF-kappaB cascadeGOMF 0.0012 0.1718 5 49 lipid transporter activityGOBP 0.0019 0.1748 28 993 intracellular signaling cascadeGOBP 0.0047 0.1748 68 3246 regulation of cellular processGOBP 0.0065 0.1748 112 5957 primary metabolic processGOBP 0.0075 0.1748 112 5980 cellular metabolic processGOBP 0.0080 0.1748 71 3492 regulation of biological processGOBP 0.0089 0.1748 4 52 antigen processing and presentationGOBP 0.0093 0.1748 77 3869 biological regulationGOBP 0.0094 0.1748 5 82 lipid transportGOBP 0.0123 0.1748 2 11 response to metal ionGOBP 0.0123 0.1748 2 11 positive regulation of I-kappaB kinase/NF-kappaB cascadeGOBP 0.0125 0.1748 3 31 neural crest cell developmentGOBP 0.0125 0.1748 3 31 neural crest cell differentiationGOBP 0.0134 0.1748 15 503 cell proliferationGOBP 0.0148 0.1748 3 33 antigen processing and presentation of peptide antigenGOBP 0.0155 0.1748 4 61 regulation of protein amino acid phosphorylationGOBP 0.0157 0.1748 119 6550 metabolic processGOBP 0.0163 0.1748 4 62 regulation of MAP kinase activityGOBP 0.0172 0.1748 2 13 embryonic forelimb morphogenesisGOBP 0.0174 0.1748 3 35 I-kappaB kinase/NF-kappaB cascadeGOBP 0.0178 0.1748 21 815 positive regulation of cellular processGOBP 0.0181 0.1748 7 170 heart developmentGOBP 0.0191 0.1748 76 3923 biopolymer metabolic processGOBP 0.0198 0.1748 2 14 tricarboxylic acid cycle intermediate metabolic processGOBP 0.0198 0.1748 2 14 response to inorganic substanceGOBP 0.0198 0.1748 2 14 dicarboxylic acid metabolic processGOBP 0.0199 0.1748 12 388 regulation of signal transduction

Gastroc – modules

Insulin traitchromosomes

14

2

12

1619

17

9

Gastroc – enrichment for modules

chromosomes

Insulin

Module Pvalue Qvalue Count Size TermGREEN 0.0157 0.1870 1 15 vacuolar transport

0.0157 0.1870 1 15 lamellipodium biogenesis0.0167 0.1870 1 16 activated T cell proliferation

YELLOW 0.0175 0.0472 1 13 regulation of protein polymerization0.0177 0.0472 13 5957 primary metabolic process0.0183 0.0472 13 5980 cellular metabolic process

0.0188 0.0472 2 157regulation of small GTPase mediated signal transduction

BLUE 0.0088 0.0231 13 3869 biological regulation0.0102 0.0231 2 85 positive regulation of protein kinase activity0.0114 0.0231 2 90 positive regulation of kinase activity0.0116 0.0231 2 91 positive regulation of transferase activity0.0161 0.0231 2 108 negative regulation of signal transduction0.0180 0.0231 11 3246 regulation of cellular process

RED 0.0188 0.1749 1 12 response to osmotic stress0.0266 0.1930 1 17 gluconeogenesis

0.0281 0.1930 1 18antigen processing and presentation of peptide antigen via MHC class I

BLACK 0.0058 0.0137 1 11positive regulation of I-kappaB kinase/NF-kappaB cascade

0.0074 0.0137 1 14 heart looping

0.0074 0.0137 1 14 regulation of I-kappaB kinase/NF-kappaB cascadeTURQUOISE 0.0013 0.0692 17 1294 post-translational protein modification

0.0018 0.0692 36 3923 biopolymer metabolic process0.0024 0.0692 18 1488 protein modification process0.0032 0.0692 18 1525 biopolymer modification

BROWN 0.0003 0.0105 2 11 response to metal ion0.0006 0.0151 2 14 response to inorganic substance

0.0007 0.0159 2 16antigen processing and presentation of peptide antigen via MHC class II

0.0007 0.0159 2 16antigen processing and presentation of exogenous peptide antigen via MHC class II

0.0008 0.0163 2 17antigen processing and presentation of peptide or polysaccharide antigen via MHC class II

0.0009 0.0168 2 18antigen processing and presentation of exogenous peptide antigen

0.0013 0.0212 2 21 response to toxin

0.0016 0.0226 2 23antigen processing and presentation of exogenous antigen

PINK 0.0016 0.0153 2 82 hormone metabolic process0.0083 0.0163 1 11 sequestering of lipid0.0090 0.0173 1 12 negative regulation of hydrolase activity0.0097 0.0176 1 13 proximal/distal pattern formation0.0097 0.0176 1 13 embryonic forelimb morphogenesis

4 tissues combined – modules

turquoise blue brown yellow green red black pink magenta purple greenyellow tan salmon total adipose 63 20 33 68 43 33 164 32 53 34 40 3 19 605 gastroc 83 8 96 35 56 31 13 28 9 12 31 1 1 404 islet 546 308 46 165 132 198 58 88 149 143 43 106 1 1983 liver 17 12 128 33 41 9 23 98 11 19 45 1 48 485 total 709 348 303 301 272 271 258 246 222 208 159 111 69 3477

Insulin trait

Insulin