Genome-wide association study of serum creatinine levels during vancomycin therapy

Sara L. Van Driest; Tracy L. McGregor; Digna R. Velez Edwards; Ben R. Saville; Terrie E. Kitchner; Scott J. Hebbring; Murray Brilliant; Hayan Jouni; Iftikhar J. Kullo; C. Buddy Creech; Prince J. Kannankeril; Susan I. Vear; Kyle B. Brothers; Erica A. Bowton; Christian M. Shaffer; Neelam Patel; Jessica T. Delaney; Yuki Bradford; Sarah Wilson; Lana M. Olson; Dana C. Crawford; Amy L. Potts; Richard H. Ho; Dan M. Roden; Josh C. Denny

doi:10.1371/journal.pone.0127791

Genome-wide association study of serum creatinine levels during vancomycin therapy

Sara L. Van Driest, Tracy L. McGregor, Digna R. Velez Edwards, Ben R. Saville, Terrie E. Kitchner, Scott J. Hebbring, Murray Brilliant, Hayan Jouni, Iftikhar J. Kullo, C. Buddy Creech, Prince J. Kannankeril, Susan I. Vear, Kyle B. Brothers, Erica A. Bowton, Christian M. Shaffer, Neelam Patel, Jessica T. Delaney, Yuki Bradford, Sarah Wilson, Lana M. OlsonDana C. Crawford, Amy L. Potts, Richard H. Ho, Dan M. Roden, Josh C. Denny

Cardiovascular Medicine

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

14 Scopus citations

Abstract

Vancomycin, a commonly used antibiotic, can be nephrotoxic. Known risk factors such as age, creatinine clearance, vancomycin dose / dosing interval, and concurrent nephrotoxic medications fail to accurately predict nephrotoxicity. To identify potential genomic risk factors, we performed a genome-wide association study (GWAS) of serum creatinine levels while on vancomycin in 489 European American individuals and validated findings in three independent cohorts totaling 439 European American individuals. In primary analyses, the chromosome 6q22.31 locus was associated with increased serum creatinine levels while on vancomycin therapy (most significant variant rs2789047, risk allele A, β = -0.06, p = 1.1 × 10^-7). SNPs in this region had consistent directions of effect in the validation cohorts, with a meta-p of 1.1 × 10^-7. Variation in this region on chromosome 6, which includes the genes TBC1D32/C6orf170 and GJA1 (encoding connexin43), may modulate risk of vancomycin-induced kidney injury.

Original language	English (US)
Article number	e0127791
Journal	PloS one
Volume	10
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0127791
State	Published - Jun 1 2015

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Van Driest, S. L., McGregor, T. L., Velez Edwards, D. R., Saville, B. R., Kitchner, T. E., Hebbring, S. J., Brilliant, M., Jouni, H., Kullo, I. J., Creech, C. B., Kannankeril, P. J., Vear, S. I., Brothers, K. B., Bowton, E. A., Shaffer, C. M., Patel, N., Delaney, J. T., Bradford, Y., Wilson, S., ... Denny, J. C. (2015). Genome-wide association study of serum creatinine levels during vancomycin therapy. PloS one, 10(6), Article e0127791. https://doi.org/10.1371/journal.pone.0127791

Van Driest, SL, McGregor, TL, Velez Edwards, DR, Saville, BR, Kitchner, TE, Hebbring, SJ, Brilliant, M, Jouni, H, Kullo, IJ, Creech, CB, Kannankeril, PJ, Vear, SI, Brothers, KB, Bowton, EA, Shaffer, CM, Patel, N, Delaney, JT, Bradford, Y, Wilson, S, Olson, LM, Crawford, DC, Potts, AL, Ho, RH, Roden, DM & Denny, JC 2015, 'Genome-wide association study of serum creatinine levels during vancomycin therapy', PloS one, vol. 10, no. 6, e0127791. https://doi.org/10.1371/journal.pone.0127791

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title = "Genome-wide association study of serum creatinine levels during vancomycin therapy",

abstract = "Vancomycin, a commonly used antibiotic, can be nephrotoxic. Known risk factors such as age, creatinine clearance, vancomycin dose / dosing interval, and concurrent nephrotoxic medications fail to accurately predict nephrotoxicity. To identify potential genomic risk factors, we performed a genome-wide association study (GWAS) of serum creatinine levels while on vancomycin in 489 European American individuals and validated findings in three independent cohorts totaling 439 European American individuals. In primary analyses, the chromosome 6q22.31 locus was associated with increased serum creatinine levels while on vancomycin therapy (most significant variant rs2789047, risk allele A, β = -0.06, p = 1.1 × 10-7). SNPs in this region had consistent directions of effect in the validation cohorts, with a meta-p of 1.1 × 10-7. Variation in this region on chromosome 6, which includes the genes TBC1D32/C6orf170 and GJA1 (encoding connexin43), may modulate risk of vancomycin-induced kidney injury.",

author = "{Van Driest}, {Sara L.} and McGregor, {Tracy L.} and {Velez Edwards}, {Digna R.} and Saville, {Ben R.} and Kitchner, {Terrie E.} and Hebbring, {Scott J.} and Murray Brilliant and Hayan Jouni and Kullo, {Iftikhar J.} and Creech, {C. Buddy} and Kannankeril, {Prince J.} and Vear, {Susan I.} and Brothers, {Kyle B.} and Bowton, {Erica A.} and Shaffer, {Christian M.} and Neelam Patel and Delaney, {Jessica T.} and Yuki Bradford and Sarah Wilson and Olson, {Lana M.} and Crawford, {Dana C.} and Potts, {Amy L.} and Ho, {Richard H.} and Roden, {Dan M.} and Denny, {Josh C.}",

note = "Publisher Copyright: {\textcopyright} 2015 Van Driest et al. 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.",

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AU - Van Driest, Sara L.

AU - McGregor, Tracy L.

AU - Velez Edwards, Digna R.

AU - Saville, Ben R.

AU - Kitchner, Terrie E.

AU - Hebbring, Scott J.

AU - Brilliant, Murray

AU - Jouni, Hayan

AU - Kullo, Iftikhar J.

AU - Creech, C. Buddy

AU - Kannankeril, Prince J.

AU - Vear, Susan I.

AU - Brothers, Kyle B.

AU - Bowton, Erica A.

AU - Shaffer, Christian M.

AU - Patel, Neelam

AU - Delaney, Jessica T.

AU - Bradford, Yuki

AU - Wilson, Sarah

AU - Olson, Lana M.

AU - Crawford, Dana C.

AU - Potts, Amy L.

AU - Ho, Richard H.

AU - Roden, Dan M.

AU - Denny, Josh C.

N1 - Publisher Copyright: © 2015 Van Driest et al. 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.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Vancomycin, a commonly used antibiotic, can be nephrotoxic. Known risk factors such as age, creatinine clearance, vancomycin dose / dosing interval, and concurrent nephrotoxic medications fail to accurately predict nephrotoxicity. To identify potential genomic risk factors, we performed a genome-wide association study (GWAS) of serum creatinine levels while on vancomycin in 489 European American individuals and validated findings in three independent cohorts totaling 439 European American individuals. In primary analyses, the chromosome 6q22.31 locus was associated with increased serum creatinine levels while on vancomycin therapy (most significant variant rs2789047, risk allele A, β = -0.06, p = 1.1 × 10-7). SNPs in this region had consistent directions of effect in the validation cohorts, with a meta-p of 1.1 × 10-7. Variation in this region on chromosome 6, which includes the genes TBC1D32/C6orf170 and GJA1 (encoding connexin43), may modulate risk of vancomycin-induced kidney injury.

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Genome-wide association study of serum creatinine levels during vancomycin therapy

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