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APOL1 Kidney Risk Variants and Cardiovascular Disease: An Individual Participant Data Meta-Analysis.

  • Grams, Morgan E1, 2, 3
  • Surapaneni, Aditya2, 3
  • Ballew, Shoshana H2, 3
  • Appel, Lawrence J2, 3
  • Boerwinkle, Eric4
  • Boulware, L Ebony5
  • Chen, Teresa K6, 2
  • Coresh, Josef2, 3
  • Cushman, Mary7, 8
  • Divers, Jasmin9
  • Gutiérrez, Orlando M7, 10
  • Irvin, Marguerite R7, 10
  • Ix, Joachim H11, 12
  • Kopp, Jeffrey B13
  • Kuller, Lewis H14
  • Langefeld, Carl D9
  • Lipkowitz, Michael S15
  • Mukamal, Kenneth J16
  • Musani, Solomon K17
  • Naik, Rakhi P18
  • And 9 more
  • 1 Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; [email protected]
  • 2 Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland.
  • 3 Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
  • 4 Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas.
  • 5 Division of General Internal Medicine, Duke University School of Medicine, Durham, North Carolina.
  • 6 Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • 7 Departments of Medicine and.
  • 8 Pathology and Laboratory Medicine, Larner College of Medicine at the University of Vermont, Colchester, Vermont.
  • 9 Department of Biostatistics and Data Science, Division of Public Health Sciences and.
  • 10 Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama.
  • 11 Division of Nephrology-Hypertension, Department of Medicine, University of California, San Diego, California.
  • 12 Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, California.
  • 13 Kidney Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
  • 14 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • 15 Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, DC.
  • 16 Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. , (Israel)
  • 17 Department of Medicine and.
  • 18 Department of Medicine, Division of Hematology, Johns Hopkins Medicine, Baltimore, Maryland.
  • 19 Kidney Health Research Collaborative, Department of Medicine, University of California, San Francisco, California.
  • 20 Department of Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, California.
  • 21 Cricket Health Inc, San Francisco, California.
  • 22 Premier Applied Sciences, Premier, Inc., Charlotte, North Carolina.
  • 23 Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.
  • 24 Molecular Genetic Epidemiology Section, Basic Research Laboratory, Basic Science Program, National Cancer Institute Leidos Biomedical Research, Frederick National Laboratory, Frederick, Maryland.
  • 25 Division of Nephrology, Veterans Affairs Puget Sound Health Care Center, Seattle, Washington; and.
  • 26 Kidney Research Institute, University of Washington, Seattle, Washington.
  • 27 Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Published Article
Journal of the American Society of Nephrology
American Society of Nephrology
Publication Date
Oct 01, 2019
DOI: 10.1681/ASN.2019030240
PMID: 31383730


Two coding variants in the apo L1 gene (APOL1) are strongly associated with kidney disease in blacks. Kidney disease itself increases the risk of cardiovascular disease, but whether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results. We conducted a two-stage individual participant data meta-analysis to assess the association of APOL1 kidney-risk variants with adjudicated cardiovascular disease events and death, independent of kidney measures. The analysis included 21,305 blacks from eight large cohorts. Over 8.9±5.0 years of follow-up, 2076 incident cardiovascular disease events occurred in the 16,216 participants who did not have cardiovascular disease at study enrollment. In fully-adjusted analyses, individuals possessing two APOL1 kidney-risk variants had similar risk of incident cardiovascular disease (coronary heart disease, myocardial infarction, stroke and heart failure; hazard ratio 1.11, 95% confidence interval, 0.96 to 1.28) compared to individuals with zero or one kidney-risk variant. The risk of coronary heart disease, myocardial infarction, stroke and heart failure considered individually was also comparable by APOL1 genotype. APOL1 genotype was also not associated with death. There was no difference in adjusted associations by level of kidney function, age, diabetes status, or body-mass index. In this large, two-stage individual participant data meta-analysis, APOL1 kidney-risk variants were not associated with incident cardiovascular disease or death independent of kidney measures. Copyright © 2019 by the American Society of Nephrology.

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