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Mapping the genetic architecture of gene expression in human liver

Schadt, Eric E ; Molony, Cliona ; Chudin, Eugene ; Hao, Ke ; Yang, Xia ; Lum, Pek Y ; Kasarskis, Andrew ; Zhang, Bin ; Wang, Susanna ; Suver, Christine ; Zhu, Jun ; Millstein, Joshua ; Sieberts, Solveig ; Lamb, John ; GuhaThakurta, Debraj ; Derry, Jonathan ; Storey, John D ; Avila-Campillo, Iliana ; Kruger, Mark J ; Johnson, Jason M ; Rohl, Carol A ; van Nas, Atila ; Mehrabian, Margarete ; Drake, Thomas A ; Lusis, Aldons J ; Smith, Ryan C ; Guengerich, F Peter ; Strom, Stephen C ; Schuetz, Erin ; Rushmore, Thomas H ; Ulrich, Roger Abecassis, Goncalo

PLoS biology, 2008-05, Vol.6 (5), p.e107-e107 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Mapping the genetic architecture of gene expression in human liver
Autor: Schadt, Eric E ; Molony, Cliona ; Chudin, Eugene ; Hao, Ke ; Yang, Xia ; Lum, Pek Y ; Kasarskis, Andrew ; Zhang, Bin ; Wang, Susanna ; Suver, Christine ; Zhu, Jun ; Millstein, Joshua ; Sieberts, Solveig ; Lamb, John ; GuhaThakurta, Debraj ; Derry, Jonathan ; Storey, John D ; Avila-Campillo, Iliana ; Kruger, Mark J ; Johnson, Jason M ; Rohl, Carol A ; van Nas, Atila ; Mehrabian, Margarete ; Drake, Thomas A ; Lusis, Aldons J ; Smith, Ryan C ; Guengerich, F Peter ; Strom, Stephen C ; Schuetz, Erin ; Rushmore, Thomas H ; Ulrich, Roger
Abecassis, Goncalo
Assuntos: Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Architecture ; Cardiovascular Disorders ; Child ; Child, Preschool ; Cholesterol, LDL - blood ; Cholesterol, LDL - genetics ; Computational Biology ; Coronary Artery Disease - genetics ; Coronary vessels ; Deoxyribonucleic acid ; Diabetes ; Diabetes and Endocrinology ; Diabetes Mellitus, Type 1 - genetics ; DNA ; Female ; Gene expression ; Gene Expression Profiling ; Gene loci ; Genes, MHC Class II - genetics ; Genetic Predisposition to Disease - genetics ; Genetics ; Genetics and Genomics ; Genome, Human ; Genomes ; Genomics ; Genotype ; Grants ; Humans ; Infant ; Liver - metabolism ; Male ; Mice ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide - genetics ; Proteins ; Quantitative Trait Loci - genetics ; RNA, Messenger - analysis ; RNA, Messenger - genetics ; Studies ; Transcription, Genetic - genetics
É parte de: PLoS biology, 2008-05, Vol.6 (5), p.e107-e107
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: Genetic variants that are associated with common human diseases do not lead directly to disease, but instead act on intermediate, molecular phenotypes that in turn induce changes in higher-order disease traits. Therefore, identifying the molecular phenotypes that vary in response to changes in DNA and that also associate with changes in disease traits has the potential to provide the functional information required to not only identify and validate the susceptibility genes that are directly affected by changes in DNA, but also to understand the molecular networks in which such genes operate and how changes in these networks lead to changes in disease traits. Toward that end, we profiled more than 39,000 transcripts and we genotyped 782,476 unique single nucleotide polymorphisms (SNPs) in more than 400 human liver samples to characterize the genetic architecture of gene expression in the human liver, a metabolically active tissue that is important in a number of common human diseases, including obesity, diabetes, and atherosclerosis. This genome-wide association study of gene expression resulted in the detection of more than 6,000 associations between SNP genotypes and liver gene expression traits, where many of the corresponding genes identified have already been implicated in a number of human diseases. The utility of these data for elucidating the causes of common human diseases is demonstrated by integrating them with genotypic and expression data from other human and mouse populations. This provides much-needed functional support for the candidate susceptibility genes being identified at a growing number of genetic loci that have been identified as key drivers of disease from genome-wide association studies of disease. By using an integrative genomics approach, we highlight how the gene RPS26 and not ERBB3 is supported by our data as the most likely susceptibility gene for a novel type 1 diabetes locus recently identified in a large-scale, genome-wide association study. We also identify SORT1 and CELSR2 as candidate susceptibility genes for a locus recently associated with coronary artery disease and plasma low-density lipoprotein cholesterol levels in the process.
Editor: United States: Public Library of Science
Idioma: Inglês

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Mapping the genetic architecture of gene expression in human liver

United States: Public Library of Science

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