Integration of Multi-omics Data from Mouse Diversity Panel Highlights Mitochondrial Dysfunction in Non-alcoholic Fatty Liver Disease

Adams, 2005, The natural history of nonalcoholic fatty liver disease: a population-based cohort study, Gastroenterology, 129, 113, 10.1053/j.gastro.2005.04.014 Alpaydin, 2010 Arneson, 2016, Mergeomics: a web server for identifying pathological pathways, networks, and key regulators via multidimensional data integration, BMC Genomics, 17, 722, 10.1186/s12864-016-3057-8 Begriche, 2006, Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it, Mitochondrion, 6, 1, 10.1016/j.mito.2005.10.004 Begriche, 2013, Mitochondrial adaptations and dysfunctions in nonalcoholic fatty liver disease, Hepatology, 58, 1497, 10.1002/hep.26226 Bennett, 2010, A high-resolution association mapping panel for the dissection of complex traits in mice, Genome Res., 20, 281, 10.1101/gr.099234.109 Bennett, 2013, Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation, Cell Metab, 17, 49, 10.1016/j.cmet.2012.12.011 Bhatnagar, 2014 Boyle, 2017, An expanded view of complex traits: from polygenic to omnigenic, Cell, 169, 1177, 10.1016/j.cell.2017.05.038 Browning, 2004, Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity, Hepatology, 40, 1387, 10.1002/hep.20466 Chakravarthy, 2009, Identification of a physiologically relevant endogenous ligand for PPARalpha in liver, Cell, 138, 476, 10.1016/j.cell.2009.05.036 Chambers, 2011, Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma, Nat. Genet., 43, 1131, 10.1038/ng.970 Chang, 2015, Second-generation PLINK: rising to the challenge of larger and richer datasets, Gigascience, 4, 7, 10.1186/s13742-015-0047-8 Crystal, 2014, Adenovirus: the first effective in vivo gene delivery vector, Hum. Gene Ther., 25, 3, 10.1089/hum.2013.2527 de Alwis, 2008, Non-alcoholic fatty liver disease: the mist gradually clears, J. Hepatol., 48, S104, 10.1016/j.jhep.2008.01.009 Derry, 2010, Identification of genes and networks driving cardiovascular and metabolic phenotypes in a mouse F2 intercross, PLoS One, 5, e14319, 10.1371/journal.pone.0014319 Ding, 2015, Mitofilin and CHCHD6 physically interact with Sam50 to sustain cristae structure, Sci. Rep., 5, 16064, 10.1038/srep16064 Emilsson, 2008, Genetics of gene expression and its effect on disease, Nature, 452, 423, 10.1038/nature06758 Folch, 1957, A simple method for the isolation and purification of total lipides from animal tissues, J. Biol. Chem., 226, 497, 10.1016/S0021-9258(18)64849-5 Hardy, 2016, Nonalcoholic fatty liver disease: pathogenesis and disease spectrum, Annu. Rev. Pathol. Mech. Dis., 11, 451, 10.1146/annurev-pathol-012615-044224 Hill-Baskin, 2009, Diet-induced hepatocellular carcinoma in genetically predisposed mice, Hum. Mol. Genet., 18, 2975, 10.1093/hmg/ddp236 Hui, 2015, The genetic architecture of NAFLD among inbred strains of mice, Elife, 4, e05607, 10.7554/eLife.05607 Huynen, 2016, Evolution and structural organization of the mitochondrial contact site (MICOS) complex and the mitochondrial intermembrane space bridging (MIB) complex, Biochim. Biophys. Acta, 1863, 91, 10.1016/j.bbamcr.2015.10.009 Kawano, 2013, Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease, J. Gastroenterol., 48, 434, 10.1007/s00535-013-0758-5 Kitamoto, 2013, Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan, Hum. Genet., 132, 783, 10.1007/s00439-013-1294-3 Kopec, 2011, Nonalcoholic fatty liver disease: a review of the spectrum of disease, diagnosis, and therapy, Nutr. Clin. Pract., 26, 565, 10.1177/0884533611419668 Kozlitina, 2014, Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease, Nat. Genet., 46, 352, 10.1038/ng.2901 Langfelder, 2008, WGCNA: an R package for weighted correlation network analysis, BMC Bioinformatics, 9, 559, 10.1186/1471-2105-9-559 Lee, 2017, Network analyses identify liver-specific targets for treating liver diseases, Mol. Syst. Biol., 13, 938, 10.15252/msb.20177703 Leek, 2012, The SVA package for removing batch effects and other unwanted variation in high-throughput experiments, Bioinformatics, 28, 882, 10.1093/bioinformatics/bts034 Listgarten, 2012, Improved linear mixed models for genome-wide association studies, Nat. Methods, 9, 525, 10.1038/nmeth.2037 Mäkinen, 2014, Integrative genomics reveals novel molecular pathways and gene networks for coronary artery disease, PLoS Genet., 10, e1004502, 10.1371/journal.pgen.1004502 Marchesini, 2003, Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome, Hepatology, 37, 917, 10.1053/jhep.2003.50161 McCullough, 2004, The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease, Clin. Liver Dis., 8, 521, 10.1016/j.cld.2004.04.004 Montgomery, 2013, Mouse strain-dependent variation in obesity and glucose homeostasis in response to high-fat feeding, Diabetologia, 56, 1129, 10.1007/s00125-013-2846-8 Nolan, 2009, Lipotoxicity: why do saturated fatty acids cause and monounsaturates protect against it?, J. Gastroenterol. Hepatol., 24, 703, 10.1111/j.1440-1746.2009.05823.x Parks, 2013, Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice, Cell Metab, 17, 141, 10.1016/j.cmet.2012.12.007 Pessayre, 2005, NASH: a mitochondrial disease, J. Hepatol., 42, 928, 10.1016/j.jhep.2005.03.004 Piñero, 2015, DisGeNET: a discovery platform for the dynamical exploration of human diseases and their genes, Database (Oxford), 2015, bav028, 10.1093/database/bav028 Ratziu, 2010, A position statement on NAFLD/NASH based on the EASL 2009 special conference, J. Hepatol., 53, 372, 10.1016/j.jhep.2010.04.008 Rogers, 2011, High throughput microplate respiratory measurements using minimal quantities of isolated mitochondria, PLoS One, 6, e21746, 10.1371/journal.pone.0021746 Schadt, 2008, Mapping the genetic architecture of gene expression in human liver, PLoS Biol., 6, 1020, 10.1371/journal.pbio.0060107 Shu, 2016, Mergeomics: multidimensional data integration to identify pathogenic perturbations to biological systems, BMC Genomics, 17, 874, 10.1186/s12864-016-3198-9 Shu, 2017, Shared genetic regulatory networks for cardiovascular disease and type 2 diabetes in multiple populations of diverse ethnicities in the United States, PLoS Genet., 13, e1007040, 10.1371/journal.pgen.1007040 Sobaniec-Lotowska, 2003, Ultrastructure of hepatocyte mitochondria in nonalcoholic steatohepatitis in pediatric patients: usefulness of electron microscopy in the diagnosis of the disease, Am. J. Gastroenterol., 98, 1664, 10.1111/j.1572-0241.2003.07561.x Song, 2015, Multiscale embedded gene co-expression network analysis, PLoS Comput. Biol., 11, e1004574, 10.1371/journal.pcbi.1004574 Storey, 2003, Statistical significance for genomewide studies, Proc. Natl. Acad. Sci. USA, 100, 9440, 10.1073/pnas.1530509100 Subramanian, 2005, {G}ene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles, Proc. Natl. Acad. Sci. USA, 102, 15545, 10.1073/pnas.0506580102 Tu, 2012, Integrative analysis of a cross-loci regulation network identifies app as a gene regulating insulin secretion from pancreatic islets, PLoS Genet., 8, e1003107, 10.1371/journal.pgen.1003107 van der Laan, 2016, Mitochondrial contact site and cristae organizing system, Curr. Opin. Cell Biol., 41, 33, 10.1016/j.ceb.2016.03.013 Van Nas, 2010, Expression quantitative trait loci: replication, tissue- and sex-specificity in mice, Genetics, 185, 1059, 10.1534/genetics.110.116087 Vernon, 2011, Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults, Aliment. Pharmacol. Ther., 34, 274, 10.1111/j.1365-2036.2011.04724.x Wang, 2007, Identification of pathways for atherosclerosis in mice: integration of quantitative trait locus analysis and global gene expression data, Circ. Res., 101, e11, 10.1161/CIRCRESAHA.107.152975 Williams, 2016, Systems proteomics of liver mitochondria function, Science, 352, aad0189, 10.1126/science.aad0189 Wu, 2013, Thyroid hormone-responsive SPOT 14 homolog promotes hepatic lipogenesis, and its expression is regulated by Liver X receptor α through a sterol regulatory element-binding protein 1c-dependent mechanism in mice, Hepatology, 58, 617, 10.1002/hep.26272 Wu, 2007, Multiparameter metabolic analysis reveals a close link between attenuated mitochondrial bioenergetic function and enhanced glycolysis dependency in human tumor cells, Am. J. Physiol. Cell Physiol., 292, C125, 10.1152/ajpcell.00247.2006 Yang, 2009, A customized and versatile high-density genotyping array for the mouse, Nat. Methods, 6, 663, 10.1038/nmeth.1359 Yang, 2006, Tissue-specific expression and regulation of sexually dimorphic genes in mice, Genome Res., 16, 995, 10.1101/gr.5217506 Ye, 2012, Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction, BMC Bioinformatics, 13, 134, 10.1186/1471-2105-13-134 Zhao, 2016, Network-based identification and prioritization of key regulators of coronary artery disease loci, Arterioscler. Thromb. Vasc. Biol., 36, 928, 10.1161/ATVBAHA.115.306725 Zhong, 2010, Liver and adipose expression associated SNPs are enriched for association to type 2 diabetes, PLoS Genet., 6, 32, 10.1371/journal.pgen.1000932 Zhu, 2007, Increasing the power to detect causal associations by combining genotypic and expression data in segregating populations, PLoS Comput. Biol., 3, 692, 10.1371/journal.pcbi.0030069 Zhu, 2008, Integrating large-scale functional genomic data to dissect the complexity of yeast regulatory networks, Nat. Genet., 40, 854, 10.1038/ng.167