Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging

Heather E. Wheeler; E. Jeffrey Metter; Toshiko Tanaka; Devin Absher; John Higgins; Jacob M. Zahn; Julie Wilhelmy; Ronald W. Davis; Andrew Singleton; Richard M. Myers; Luigi Ferrucci; Stuart K. Kim

doi:10.1371/journal.pgen.1000685

Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging

Heather E. Wheeler, E. Jeffrey Metter, Toshiko Tanaka, Devin Absher, John Higgins, Jacob M. Zahn, Julie Wilhelmy, Ronald W. Davis, Andrew Singleton, Richard M. Myers, Luigi Ferrucci, Stuart K. Kim

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

Abstract

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 ageregulated 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.

Original language	English (US)
Article number	e1000685
Journal	PLoS Genetics
Volume	5
Issue number	10
DOIs	https://doi.org/10.1371/journal.pgen.1000685
State	Published - Oct 2009
Externally published	Yes

ASJC Scopus subject areas

Genetics
Molecular Biology
Ecology, Evolution, Behavior and Systematics
Cancer Research
Genetics(clinical)

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Wheeler, H. E., Metter, E. J., Tanaka, T., Absher, D., Higgins, J., Zahn, J. M., Wilhelmy, J., Davis, R. W., Singleton, A., Myers, R. M., Ferrucci, L., & Kim, S. K. (2009). Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging. PLoS Genetics, 5(10), Article e1000685. https://doi.org/10.1371/journal.pgen.1000685

Wheeler, HE, Metter, EJ, Tanaka, T, Absher, D, Higgins, J, Zahn, JM, Wilhelmy, J, Davis, RW, Singleton, A, Myers, RM, Ferrucci, L & Kim, SK 2009, 'Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging', PLoS Genetics, vol. 5, no. 10, e1000685. https://doi.org/10.1371/journal.pgen.1000685

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abstract = "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 ageregulated 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.",

author = "Wheeler, {Heather E.} and Metter, {E. Jeffrey} and Toshiko Tanaka and Devin Absher and John Higgins and Zahn, {Jacob M.} and Julie Wilhelmy and Davis, {Ronald W.} and Andrew Singleton and Myers, {Richard M.} and Luigi Ferrucci and Kim, {Stuart K.}",

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AU - Higgins, John

AU - Zahn, Jacob M.

AU - Wilhelmy, Julie

AU - Davis, Ronald W.

AU - Singleton, Andrew

AU - Myers, Richard M.

AU - Ferrucci, Luigi

AU - Kim, Stuart K.

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Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging

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