Sequential Use of Transcriptional Profiling, Expression Quantitative Trait Mapping, and Gene Association Implicates MMP20 in Human Kidney Aging: e1000685
Kidneys age at different rates, such that some people show little or no effects of aging whereas others show rapid functional decline. We sequentially used transcriptional profiling and expression quantitative trait loci (eQTL) mapping to narrow down which genes to test for association with kidney a...
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| Veröffentlicht in: | PLoS genetics 2009-10, Vol.5 (10) |
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| container_title | PLoS genetics |
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| creator | Wheeler, Heather E Metter, E Jeffrey Tanaka, Toshiko Absher, Devin Higgins, John Zahn, Jacob M Wilhelmy, Julie Davis, Ronald W Singleton, Andrew Myers, Richard M Ferrucci, Luigi Kim, Stuart K |
| description | Kidneys age at different rates, such that some people show little or no effects of aging whereas others show rapid functional decline. We sequentially used transcriptional profiling and expression quantitative trait loci (eQTL) mapping to narrow down which genes to test for association with kidney aging. We first performed whole-genome transcriptional profiling to find 630 genes that change expression with age in the kidney. Using two methods to detect eQTLs, we found 101 of these age-regulated genes contain expression-associated SNPs. We tested the eQTLs for association with kidney aging, measured by glomerular filtration rate (GFR) using combined data from the Baltimore Longitudinal Study of Aging (BLSA) and the InCHIANTI study. We found a SNP association (rs1711437 in MMP20) with kidney aging (uncorrected p = 3.6×10-5, empirical p = 0.01) that explains 1%-2% of the variance in GFR among individuals. The results of this sequential analysis may provide the first evidence for a gene association with kidney aging in humans. |
| doi_str_mv | 10.1371/journal.pgen.1000685 |
| format | Article |
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We sequentially used transcriptional profiling and expression quantitative trait loci (eQTL) mapping to narrow down which genes to test for association with kidney aging. We first performed whole-genome transcriptional profiling to find 630 genes that change expression with age in the kidney. Using two methods to detect eQTLs, we found 101 of these age-regulated genes contain expression-associated SNPs. We tested the eQTLs for association with kidney aging, measured by glomerular filtration rate (GFR) using combined data from the Baltimore Longitudinal Study of Aging (BLSA) and the InCHIANTI study. We found a SNP association (rs1711437 in MMP20) with kidney aging (uncorrected p = 3.6×10-5, empirical p = 0.01) that explains 1%-2% of the variance in GFR among individuals. The results of this sequential analysis may provide the first evidence for a gene association with kidney aging in humans.</description><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1000685</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Age ; Aging ; Genetics ; Genomes ; Hypotheses ; Hypothesis testing ; Population ; Studies</subject><ispartof>PLoS genetics, 2009-10, Vol.5 (10)</ispartof><rights>2009 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Citation: Wheeler HE, Metter EJ, Tanaka T, Absher D, Higgins J, et al. (2009) Sequential Use of Transcriptional Profiling, Expression Quantitative Trait Mapping, and Gene Association Implicates MMP20 in Human Kidney Aging. 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We sequentially used transcriptional profiling and expression quantitative trait loci (eQTL) mapping to narrow down which genes to test for association with kidney aging. We first performed whole-genome transcriptional profiling to find 630 genes that change expression with age in the kidney. Using two methods to detect eQTLs, we found 101 of these age-regulated genes contain expression-associated SNPs. We tested the eQTLs for association with kidney aging, measured by glomerular filtration rate (GFR) using combined data from the Baltimore Longitudinal Study of Aging (BLSA) and the InCHIANTI study. We found a SNP association (rs1711437 in MMP20) with kidney aging (uncorrected p = 3.6×10-5, empirical p = 0.01) that explains 1%-2% of the variance in GFR among individuals. The results of this sequential analysis may provide the first evidence for a gene association with kidney aging in humans.</description><subject>Age</subject><subject>Aging</subject><subject>Genetics</subject><subject>Genomes</subject><subject>Hypotheses</subject><subject>Hypothesis testing</subject><subject>Population</subject><subject>Studies</subject><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNqNj0FLAzEQhYMoWKv_wMOAV7smpnG7xyLViiy0WM9l2M4uKdskZrKiv8K_3K3Uu6c3PN73mCfEtZKZ0rm62_ouOmyz0JDLlJTyYWJOxEAZo0f5WI5P_25dyHNxwbyVUptJkQ_Ezxt9dOSSxRbemcDXsIrouIo2JOv7VlhEX9vWuuYWZl8hEnPvw7LDnkqY7CcdEJugxBB-Y-g28EyOYMrsK4uHInjZhdZWmIihLBf3EqyDebdDB6924-gbpk0PX4qzGlumq6MOxc3TbPU4H4Xo-0c5rY9jea200kaZQhv9v9QevY1e0A</recordid><startdate>20091001</startdate><enddate>20091001</enddate><creator>Wheeler, Heather E</creator><creator>Metter, E Jeffrey</creator><creator>Tanaka, Toshiko</creator><creator>Absher, Devin</creator><creator>Higgins, John</creator><creator>Zahn, Jacob M</creator><creator>Wilhelmy, Julie</creator><creator>Davis, Ronald W</creator><creator>Singleton, Andrew</creator><creator>Myers, Richard M</creator><creator>Ferrucci, Luigi</creator><creator>Kim, Stuart K</creator><general>Public Library of Science</general><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope></search><sort><creationdate>20091001</creationdate><title>Sequential Use of Transcriptional Profiling, Expression Quantitative Trait Mapping, and Gene Association Implicates MMP20 in Human Kidney Aging</title><author>Wheeler, Heather E ; 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We sequentially used transcriptional profiling and expression quantitative trait loci (eQTL) mapping to narrow down which genes to test for association with kidney aging. We first performed whole-genome transcriptional profiling to find 630 genes that change expression with age in the kidney. Using two methods to detect eQTLs, we found 101 of these age-regulated genes contain expression-associated SNPs. We tested the eQTLs for association with kidney aging, measured by glomerular filtration rate (GFR) using combined data from the Baltimore Longitudinal Study of Aging (BLSA) and the InCHIANTI study. We found a SNP association (rs1711437 in MMP20) with kidney aging (uncorrected p = 3.6×10-5, empirical p = 0.01) that explains 1%-2% of the variance in GFR among individuals. 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| subjects | Age Aging Genetics Genomes Hypotheses Hypothesis testing Population Studies |
| title | Sequential Use of Transcriptional Profiling, Expression Quantitative Trait Mapping, and Gene Association Implicates MMP20 in Human Kidney Aging: e1000685 |
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