Genome-wide association of copy number polymorphisms and kidney function

Man Li, Jacob Carey, Stephen Cristiano, Katalin Susztak, Josef Coresh, Eric Boerwinkle, Wen Hong L Kao, Terri L Beaty, Anna Köttgen, Robert B Scharpf

Research output: Contribution to journalArticle

Abstract

Genome-wide association studies (GWAS) using single nucleotide polymorphisms (SNPs) have identified more than 50 loci associated with estimated glomerular filtration rate (eGFR), a measure of kidney function. However, significant SNPs account for a small proportion of eGFR variability. Other forms of genetic variation have not been comprehensively evaluated for association with eGFR. In this study, we assess whether changes in germline DNA copy number are associated with GFR estimated from serum creatinine, eGFRcrea. We used hidden Markov models (HMMs) to identify copy number polymorphic regions (CNPs) from highthroughput SNP arrays for 2,514 African (AA) and 8,645 European ancestry (EA) participants in the Atherosclerosis Risk in Communities (ARIC) study. Separately for the EA and AA cohorts, we used Bayesian Gaussian mixture models to estimate copy number at regions identified by the HMM or previously reported in the HapMap Project. We identified 312 and 464 autosomal CNPs among individuals of EA and AA, respectively. Multivariate models adjusted for SNP-derived covariates of population structure identified one CNP in the EA cohort near genome-wide statistical significance (Bonferroni-adjusted p = 0.067) located on chromosome 5 (876-880kb). Overall, our findings suggest a limited role of CNPs in explaining eGFR variability.

Original languageEnglish (US)
Article numbere0170815
JournalPLoS One
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

DNA Copy Number Variations
glomerular filtration rate
renal function
Polymorphism
Glomerular Filtration Rate
single nucleotide polymorphism
Single Nucleotide Polymorphism
ancestry
Nucleotides
Genes
genetic polymorphism
Genome
Kidney
genome
Hidden Markov models
HapMap Project
Chromosomes, Human, Pair 5
Genome-Wide Association Study
Chromosomes
atherosclerosis

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Genome-wide association of copy number polymorphisms and kidney function. / Li, Man; Carey, Jacob; Cristiano, Stephen; Susztak, Katalin; Coresh, Josef; Boerwinkle, Eric; Kao, Wen Hong L; Beaty, Terri L; Köttgen, Anna; Scharpf, Robert B.

In: PLoS One, Vol. 12, No. 1, e0170815, 01.01.2017.

Research output: Contribution to journalArticle

Li, M, Carey, J, Cristiano, S, Susztak, K, Coresh, J, Boerwinkle, E, Kao, WHL, Beaty, TL, Köttgen, A & Scharpf, RB 2017, 'Genome-wide association of copy number polymorphisms and kidney function', PLoS One, vol. 12, no. 1, e0170815. https://doi.org/10.1371/journal.pone.0170815
Li M, Carey J, Cristiano S, Susztak K, Coresh J, Boerwinkle E et al. Genome-wide association of copy number polymorphisms and kidney function. PLoS One. 2017 Jan 1;12(1). e0170815. https://doi.org/10.1371/journal.pone.0170815
Li, Man ; Carey, Jacob ; Cristiano, Stephen ; Susztak, Katalin ; Coresh, Josef ; Boerwinkle, Eric ; Kao, Wen Hong L ; Beaty, Terri L ; Köttgen, Anna ; Scharpf, Robert B. / Genome-wide association of copy number polymorphisms and kidney function. In: PLoS One. 2017 ; Vol. 12, No. 1.
@article{5e03d38608174577a52dcfe57ec5dcd6,
title = "Genome-wide association of copy number polymorphisms and kidney function",
abstract = "Genome-wide association studies (GWAS) using single nucleotide polymorphisms (SNPs) have identified more than 50 loci associated with estimated glomerular filtration rate (eGFR), a measure of kidney function. However, significant SNPs account for a small proportion of eGFR variability. Other forms of genetic variation have not been comprehensively evaluated for association with eGFR. In this study, we assess whether changes in germline DNA copy number are associated with GFR estimated from serum creatinine, eGFRcrea. We used hidden Markov models (HMMs) to identify copy number polymorphic regions (CNPs) from highthroughput SNP arrays for 2,514 African (AA) and 8,645 European ancestry (EA) participants in the Atherosclerosis Risk in Communities (ARIC) study. Separately for the EA and AA cohorts, we used Bayesian Gaussian mixture models to estimate copy number at regions identified by the HMM or previously reported in the HapMap Project. We identified 312 and 464 autosomal CNPs among individuals of EA and AA, respectively. Multivariate models adjusted for SNP-derived covariates of population structure identified one CNP in the EA cohort near genome-wide statistical significance (Bonferroni-adjusted p = 0.067) located on chromosome 5 (876-880kb). Overall, our findings suggest a limited role of CNPs in explaining eGFR variability.",
author = "Man Li and Jacob Carey and Stephen Cristiano and Katalin Susztak and Josef Coresh and Eric Boerwinkle and Kao, {Wen Hong L} and Beaty, {Terri L} and Anna K{\"o}ttgen and Scharpf, {Robert B}",
year = "2017",
month = "1",
day = "1",
doi = "10.1371/journal.pone.0170815",
language = "English (US)",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Genome-wide association of copy number polymorphisms and kidney function

AU - Li, Man

AU - Carey, Jacob

AU - Cristiano, Stephen

AU - Susztak, Katalin

AU - Coresh, Josef

AU - Boerwinkle, Eric

AU - Kao, Wen Hong L

AU - Beaty, Terri L

AU - Köttgen, Anna

AU - Scharpf, Robert B

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Genome-wide association studies (GWAS) using single nucleotide polymorphisms (SNPs) have identified more than 50 loci associated with estimated glomerular filtration rate (eGFR), a measure of kidney function. However, significant SNPs account for a small proportion of eGFR variability. Other forms of genetic variation have not been comprehensively evaluated for association with eGFR. In this study, we assess whether changes in germline DNA copy number are associated with GFR estimated from serum creatinine, eGFRcrea. We used hidden Markov models (HMMs) to identify copy number polymorphic regions (CNPs) from highthroughput SNP arrays for 2,514 African (AA) and 8,645 European ancestry (EA) participants in the Atherosclerosis Risk in Communities (ARIC) study. Separately for the EA and AA cohorts, we used Bayesian Gaussian mixture models to estimate copy number at regions identified by the HMM or previously reported in the HapMap Project. We identified 312 and 464 autosomal CNPs among individuals of EA and AA, respectively. Multivariate models adjusted for SNP-derived covariates of population structure identified one CNP in the EA cohort near genome-wide statistical significance (Bonferroni-adjusted p = 0.067) located on chromosome 5 (876-880kb). Overall, our findings suggest a limited role of CNPs in explaining eGFR variability.

AB - Genome-wide association studies (GWAS) using single nucleotide polymorphisms (SNPs) have identified more than 50 loci associated with estimated glomerular filtration rate (eGFR), a measure of kidney function. However, significant SNPs account for a small proportion of eGFR variability. Other forms of genetic variation have not been comprehensively evaluated for association with eGFR. In this study, we assess whether changes in germline DNA copy number are associated with GFR estimated from serum creatinine, eGFRcrea. We used hidden Markov models (HMMs) to identify copy number polymorphic regions (CNPs) from highthroughput SNP arrays for 2,514 African (AA) and 8,645 European ancestry (EA) participants in the Atherosclerosis Risk in Communities (ARIC) study. Separately for the EA and AA cohorts, we used Bayesian Gaussian mixture models to estimate copy number at regions identified by the HMM or previously reported in the HapMap Project. We identified 312 and 464 autosomal CNPs among individuals of EA and AA, respectively. Multivariate models adjusted for SNP-derived covariates of population structure identified one CNP in the EA cohort near genome-wide statistical significance (Bonferroni-adjusted p = 0.067) located on chromosome 5 (876-880kb). Overall, our findings suggest a limited role of CNPs in explaining eGFR variability.

UR - http://www.scopus.com/inward/record.url?scp=85011298584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85011298584&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0170815

DO - 10.1371/journal.pone.0170815

M3 - Article

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e0170815

ER -