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Genome-Wide Association of Copy Number Polymorphisms and Kidney Function.

TitleGenome-Wide Association of Copy Number Polymorphisms and Kidney Function.
Publication TypeJournal Article
Year of Publication2017
AuthorsLi M, Carey J, Cristiano S, Susztak K, Coresh JJ, Boerwinkle E, Kao W HL, Beaty TH, Köttgen A
Secondary AuthorsScharpf RB
JournalPLoS One
Date Published2017
KeywordsAfrican Continental Ancestry Group, Atherosclerosis, DNA Copy Number Variations, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Kidney, Kidney Function Tests, Linear Models, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors

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.

Alternate JournalPLoS One
PubMed ID28135296
PubMed Central IDPMC5279752
Grant ListDP3 DK108220 / DK / NIDDK NIH HHS / United States
R01 DK087635 / DK / NIDDK NIH HHS / United States