title: Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging.
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 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 x 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.
authors.affiliation: Department of Genetics, Stanford University Medical Center, Stanford, California, USA.
authors.forename: Heather E
authors.initials: HE
authors.lastname: Wheeler
authors.forename: E Jeffrey
authors.initials: EJ
authors.lastname: Metter
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Devin
authors.initials: D
authors.lastname: Absher
authors.forename: John
authors.initials: J
authors.lastname: Higgins
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Zahn
authors.forename: Julie
authors.initials: J
authors.lastname: Wilhelmy
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Davis
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.forename: Richard M
authors.initials: RM
authors.lastname: Myers
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000375:Aging; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000502:physiology*; D053519:Matrix Metalloproteinase 20 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci
chemical_list: C507111:MMP20 protein, human; D053519:Matrix Metalloproteinase 20