title: The MYH9/APOL1 region and chronic kidney disease in European-Americans.
abstract: Polymorphisms in the MYH9 and adjacent APOL1 gene region demonstrate a strong association with non-diabetic kidney disease in African-Americans. However, it is not known to what extent these polymorphisms are present in other ethnic groups. To examine the association of genetic polymorphisms in this region with chronic kidney disease (CKD; estimated glomerular filtration rate <60 ml/min/1.73 m(2)) in individuals of European ancestry, we examined rs4821480, an MYH9 single-nucleotide polymorphism (SNP) recently identified as associated with kidney disease in African-Americans, in 13 133 participants from the Framingham Heart Study (FHS) and Atherosclerosis Risk in Communities (ARIC) Study. In addition, we further interrogated the MYH9/APOL1 gene region using 282 SNPs for association with CKD using age-, sex- and center-adjusted models and performed a meta-analysis of the results from both studies. Because of prior data linking rs4821480 and kidney disease, we used a P-value of <0.05 to test the association with CKD. In the meta-analysis, rs4821480 (minor allele frequency 4.45 and 3.96% in FHS and ARIC, respectively) was associated with higher CKD prevalence in participants free of diabetes (odds ratio 1.44; 95% confidence interval 1.15-1.80; P = 0.001). No other SNPs achieved significance after adjusting for multiple testing. Results utilizing directly genotyped data confirmed the results of the primary analysis. Recently identified APOL1 risk variants were also directly genotyped, but did not account for the observed MYH9 signal. These data suggest that the MYH9 polymorphism rs4821480 is associated with an increased risk of non-diabetic CKD in individuals of European ancestry.
authors.affiliation: National Heart, Lung and Blood Institute's Framingham Heart Study and Center for Population Studies, Framingham, MA, USA.
authors.forename: Conall M
authors.initials: CM
authors.lastname: O'Seaghdha
authors.forename: Rulan S
authors.initials: RS
authors.lastname: Parekh
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Anna
authors.initials: A
authors.lastname: Köttgen
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
mesh_terms: D015331:Cohort Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007674:Kidney Diseases / Q000208:ethnology* / Q000235:genetics*; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014481:United States; D044465:White People / Q000235:genetics
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains