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 high-throughput 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.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.|Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Jacob
authors.initials: J
authors.lastname: Carey
authors.affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Cristiano
authors.affiliation: Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Katalin
authors.initials: K
authors.lastname: Susztak
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.|Welch Center for Prevention, Epidemiology and Clinical Research, Baltimore, Maryland, United States of America.
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.affiliation: Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.|Welch Center for Prevention, Epidemiology and Clinical Research, Baltimore, Maryland, United States of America.
authors.forename: Wen Hong L
authors.initials: WH
authors.lastname: Kao
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.|Division of Genetic Epidemiology, Medical Center-University of Freiburg, Faculty of Medicine, Freiburg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Köttgen
authors.affiliation: Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Scharpf
mesh_terms: D050197:Atherosclerosis / Q000235:genetics; D044383:Black People / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005919:Glomerular Filtration Rate / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000502:physiology*; D007677:Kidney Function Tests; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics