|Plasma lipids||C, HF, ATH|
|Adiposity||C, HF, ATH|
|Blood cell levels||C, HF, ATH|
|IR||C, HF, ATH|
|Fatty liver disease||HF, ATH|
|Heart failure induced by isoproterenol||ISO|
|Liver||C, HF, ATH|
|Protein levels, liver||C|
|Gut microbiome||C, HF ATH|
|Biological scales||Various levels in the flow of information from DNA to proteins to metabolites to cell structures to cell interactions.|
|Cis-regulatory elements||Regions of DNA which regulate the transcription of genes, usually nearby, on the same DNA strand. Examples are promoters or enhancers.|
|Congenic strains||Strains in which a small region of the genome from one strain has been placed, by repeated crossing, onto the genetic background of a second strain.|
|Correlation||In statistics, a measure of the strength and direction of a linear relationship between two variables. Usually measured as a correlation coefficient.|
|eQTL||A genetic locus that controls the levels of a transcript.|
|GWAS||An examination of common genetic variation across the genome designed to identify associations with traits such as common diseases. Typically, several hundred thousand SNPs are interrogated using microarray technologies.|
|Haplotypes||Combinations of alleles at genetic loci that are inherited together.|
|Heritability||An estimate of the proportion of genetic variation in a population that is attributable to genetic variation among individuals.|
|Inbred strains||Strains in which a set of naturally occurring genetic variations have been fixed by many generations of inbreeding.|
|Linkage analysis||Analysis of the segregation patterns of alleles or loci in families or experimental crosses. Such analysis is commonly used to map genetic traits by testing whether a trait cosegregates with genetic markers whose chromosomal locations are known.|
|LD||In population genetics, LD is the nonrandom association of alleles. For example, alleles of SNPs that reside near one another on a chromosome often occur in nonrandom combinations owing to infrequent recombination. LD should not be confused with genetic linkage, which occurs when genetic loci or alleles are inherited jointly, usually because they reside on the same chromosome.|
|LD blocks||Regions of high correlation across genetic markers, which results from their linkage in cis on a chromosome and thus infrequent recombination during meiosis. LD blocks are often demarcated by recombination hot spots|
|Modules||In the context of network modeling, groups of components that are tightly connected or correlated across a set of conditions, perturbations or genetic backgrounds.|
|Natural genetic variation||Genetic variation that is present in all populations as a result of mutations that occur in the germline; the frequencies of such mutations in populations are affected by selection and by random drift. This is in contrast with experimental variation that is introduced by techniques such as gene targeting and chemical mutagenesis.|
|QTL||A genetic locus that influences complex and usually continuous traits, such as blood pressure or cholesterol levels.|
|RI strains||A set of inbred strains that is generally produced by crossing two parental inbred strains and then inbreeding random intercross progeny; they provide a permanent resource for examining the segregation of traits that differ between the parental strains.|
|Systems genetics||A global analysis of the molecular factors that underlie variability in physiological or clinical phenotypes across individuals in a population. It considers not only the underlying genetic variation but also intermediate phenotypes such as gene expression, protein levels and metabolite levels, in addition to gene-by-gene and gene-by-environment interactions.|
|Trans-regulatory factors||Factors which regulate the transcription of genes at a distance. Examples are transcription factors and microRNAs.|
High-resolution association mapping
- Iraqi F.A.
- Athamni H.
- Dorman A.
- Salymah Y.
- Tomlinson I.
- Nashif A.
- Shusterman A.
- Weiss E.
- Houri-Haddad Y.
- Mott R.
- et al.
Relevance to complex human diseases
Genetic analysis of molecular phenotypes using high throughput technologies
The flow of biologic information: from genes to molecular traits to clinical traits
TRAITS RELEVANT TO COMMON DISEASES
Obesity and dietary responsiveness
Insulin resistance and type 2 diabetes
Fatty liver disease
|Ncan||0.37||6 × 10−5||3 × 10−8||Adipose|
|Lyplal1||0.27||0.003||2 × 10−30||Liver|
- Morrison A.C.
- Felix J.F.
- Cupples L.A.
- Glazer N.L.
- Loehr L.R.
- Dehghan A.
- Demissie S.
- Bis J.C.
- Rosamond W.D.
- Aulchenko Y.S.
- et al.
Type 1 diabetes and diabetic nephropathy
Other clinical traits
Genetic control of protein abundance
Regulation of metabolism
Host-gut microbiota interactions
Blood cell levels
HMDP DATABASE AND ITS USE FOR CARDIOMETABOLIC RESEARCH
What information can be gained about your gene of interest?
What can I learn about my complex clinical trait of interest?
- A high-resolution association mapping panel for the dissection of complex traits in mice.Genome Res. 2010; 20: 281-290
- Systems genetics of metabolism: the use of the BXD murine reference panel for multiscalar integration of traits.Cell. 2012; 150: 1287-1299
- The convergence of systems and reductionist approaches in complex trait analysis.Cell. 2015; 162: 23-32
- Chromosome substitution strains: gene discovery, functional analysis, and systems studies.Mamm. Genome. 2012; 23: 693-705
- High-density genotypes of inbred mouse strains: improved power and precision of association mapping.G3 (Bethesda). 2015; 5: 2021-2026
- Mapping complex traits using families of recombinant inbred strains: an overview and example of mapping susceptibility to Candida albicans induced illness phenotypes.Pathog. Dis. 2014; 71: 234-248
- Comparative analysis of proteome and transcriptome variation in mouse.PLoS Genet. 2011; 7: e1001393
- Genetic regulation of mouse liver metabolite levels.Mol. Syst. Biol. 2014; 10: 730
Silver, L. M., 1995. Mouse Genetics: Concepts and Applications. Oxford University Press, Oxford, UK.
- Efficient control of population structure in model organism association mapping.Genetics. 2008; 178: 1709-1723
- FaST linear mixed models for genome-wide association studies.Nat. Methods. 2011; 8: 833-835
- Genetic architecture of insulin resistance in the mouse.Cell Metab. 2015; 21: 334-346
- Increasing association mapping power and resolution in mouse genetic studies through the use of meta-analysis for structured populations.Genetics. 2012; 191: 959-967
- Meta-analysis identifies gene-by-environment interactions as demonstrated in a study of 4,965 mice.PLoS Genet. 2014; 10: e1004022
- Genome-wide association study for age-related hearing loss (AHL) in the mouse: a meta-analysis.J. Assoc. Res. Otolaryngol. 2014; 15: 335-352
- Unraveling inflammatory responses using systems genetics and gene-environment interactions in macrophages.Cell. 2012; 151: 658-670
- Gene networks associated with conditional fear in mice identified using a systems genetics approach.BMC Syst. Biol. 2011; 5: 43
- Heritability and coefficient of genetic variation analyses of phenotypic traits provide strong basis for high-resolution QTL mapping in the Collaborative Cross mouse genetic reference population.Mamm. Genome. 2014; 25: 109-119
- Mouse genome-wide association and systems genetics identify Asxl2 as a regulator of bone mineral density and osteoclastogenesis.PLoS Genet. 2011; 7: e1002038
- Bicc1 is a genetic determinant of osteoblastogenesis and bone mineral density.J. Clin. Invest. 2014; 124: 2736-2749
- Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice.Cell Metab. 2013; 17: 141-152
- Genome-wide association mapping of blood cell traits in mice.Mamm. Genome. 2013; 24: 105-118
- Mapping genetic contributions to cardiac pathology induced by Beta-adrenergic stimulation in mice.Circ Cardiovasc Genet. 2015; 8: 40-49
- Allele-specific expression and eQTL analysis in mouse adipose tissue.BMC Genomics. 2014; 15: 471
- Analysis of allele-specific expression in mouse liver by RNA-Seq: a comparison with Cis-eQTL identified using genetic linkage.Genetics. 2013; 195: 1157-1166
- Systems genetics approaches to understand complex traits.Nat. Rev. Genet. 2014; 15: 34-48
- Complex genetic control of HDL levels in mice in response to an atherogenic diet. Coordinate regulation of HDL levels and bile acid metabolism.J. Clin. Invest. 1997; 99: 1406-1419
- From expression QTLs to personalized transcriptomics.Nat. Rev. Genet. 2011; 12: 277-282
- Leducq Consortium CAD Genomics. Prediction of causal candidate genes in coronary artery disease loci.Arterioscler. Thromb. Vasc. Biol. 2015; 35: 2207-2217
- An integrative genomics approach to infer causal associations between gene expression and disease.Nat. Genet. 2005; 37: 710-717
- Using genetic markers to orient the edges in quantitative trait networks: the NEO software.BMC Syst. Biol. 2008; 2: 34
- Combined expression trait correlations and expression quantitative trait locus mapping.PLoS Genet. 2006; 2: e6
- Systems-level analysis of genome-wide association data.G3 (Bethesda). 2013; 3: 119-129
- Maximal information component analysis: a novel non-linear network analysis method.Front. Genet. 2013; 4: 28
- Insights into obesity and diabetes at the intersection of mouse and human genetics.Trends Endocrinol. Metab. 2014; 25: 493-501
- ASXL2 regulates glucose, lipid, and skeletal homeostasis.Cell Reports. 2015; 11: 1625-1637
- WGCNA: an R package for weighted correlation network analysis.BMC Bioinformatics. 2008; 9: 559
- Systems genetic analysis of osteoblast-lineage cells.PLoS Genet. 2012; 8: e1003150
- Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations.Nat. Genet. 2009; 41: 157-159
- Genetic studies of body mass index yield new insights for obesity biology.Nature. 2015; 518: 197-206
- The Niemann-Pick C1 gene interacts with a high-fat diet and modifying genes to promote weight gain.Am. J. Med. Genet. A. 2011; 155A: 2317-2319
- Genetic and environmental control of host-gut microbiota interactions.Genome Res. 2015; 25: 1558-1569
- Antibiotics in early life and obesity.Nat. Rev. Endocrinol. 2015; 11: 182-190
- The genetic architecture of NAFLD among inbred strains of mice.eLife. 2015; 4: e05607
- Genomic variation associated with mortality among adults of European and African ancestry with heart failure: the cohorts for heart and aging research in genomic epidemiology consortium.Circ Cardiovasc Genet. 2010; 3: 248-255
- A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy.Eur. Heart J. 2011; 32: 1065-1076
- Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics.Proc. Natl. Acad. Sci. USA. 2007; 104: 4530-4535
- Genetic control of lipid transport in mice. I. Structural properties and polymorphisms of plasma lipoproteins.J. Biol. Chem. 1983; 258: 5063-5070
- Genetic architecture of atherosclerosis in mice: a systems genetics analysis of common inbred strains.PLoS Genet. 2015; 11: e1005711
- Cross-tissue regulatory gene networks in coronary artery disease.Cell Syst. 2016; 2: 196-208
- Expression quantitative trait loci: replication, tissue- and sex-specificity in mice.Genetics. 2010; 185: 1059-1068
- Heritability of periodontal bone loss in mice.J. Periodontal Res. 2015; 50: 730-736
- Genetic modulation of diabetic nephropathy among mouse strains with Ins2 Akita mutation.Physiol. Rep. 2014; 2: e12208
- The genetic architecture of hearing impairment in mice: evidence for frequency-specific genetic determinants.G3 (Bethesda). 2015; 5: 2329-2339
- Correction: genome-wide association study identifies Nox3 as a critical gene for susceptibility to noise-induced hearing loss.PLoS Genet. 2015; 11: e1005293
- Approaches for establishing the function of regulatory genetic variants involved in disease.Genome Med. 2014; 6: 92
- Genetic architecture of complex traits: large phenotypic effects and pervasive epistasis.Proc. Natl. Acad. Sci. USA. 2008; 105: 19910-19914
- Identification of the bile acid transporter Slco1a6 as a candidate gene that broadly affects gene expression in mouse pancreatic islets.Genetics. 2015; 201: 1253-1262
- Genetics of single-cell protein abundance variation in large yeast populations.Nature. 2014; 506: 494-497
- A map of the cis-regulatory sequences in the mouse genome.Nature. 2012; 488: 116-120
- ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome.Nature. 2012; 489: 57-74
- Open chromatin profiling in mice livers reveals unique chromatin variations induced by high fat diet.J. Biol. Chem. 2014; 289: 23557-23567
- Epigenome-wide association of liver methylation patterns and complex metabolic traits in mice.Cell Metab. 2015; 21: 905-917
- Intergenerational genomic DNA methylation patterns in mouse hybrid strains.Genome Biol. 2014; 15: R68
- Human metabolic profiles are stably controlled by genetic and environmental variation.Mol. Syst. Biol. 2011; 7: 525
- Unraveling the environmental and genetic interactions in atherosclerosis: central role of the gut microbiota.Atherosclerosis. 2015; 241: 387-399
- Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation.Cell Metab. 2013; 17: 49-60
- Transmission of atherosclerosis susceptibility with gut microbial transplantation.J. Biol. Chem. 2015; 290: 5647-5660
- Human genetics shape the gut microbiome.Cell. 2014; 159: 789-799
- Understanding the sexome: measuring and reporting sex differences in gene systems.Endocrinology. 2012; 153: 2551-2555
- Tissue-specific expression and regulation of sexually dimorphic genes in mice.Genome Res. 2006; 16: 995-1004
- Elucidating the role of gonadal hormones in sexually dimorphic gene coexpression networks.Endocrinology. 2009; 150: 1235-1249
- Seventy-five genetic loci influencing the human red blood cell.Nature. 2012; 492: 369-375
- The genetic landscape of hematopoietic stem cell frequency in mice.Stem Cell Reports. 2015; 5: 125-138
- The systems genetics resource: a web application to mine global data for complex disease traits.Front. Genet. 2013; 4: 84
- Integrating genetic and network analysis to characterize genes related to mouse weight.PLoS Genet. 2006; 2: e130
- Contrasting genetic architectures in different mouse reference populations used for studying complex traits.Genome Res. 2015; 25: 775-791
This work was supported by National Institutes of Health Grants HL28481, HL30568, HL114437, HL123295, and D094311. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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