APOL1 kidney risk variants and cardiovascular disease: An individual participant data meta-analysis

Morgan E. Grams, Aditya Surapaneni, Shoshana H. Ballew, Lawrence J. Appel, Eric Boerwinkle, L. Ebony Boulware, Teresa K. Chen, Josef Coresh, Mary Cushman, Jasmin Divers, Orlando M. Gutiérrez, Marguerite R. Irvin, Joachim H. Ix, Jeffrey B. Kopp, Lewis H. Kuller, Carl D. Langefeld, Michael S. Lipkowitz, Kenneth J. Mukamal, Solomon K. Musani, Rakhi P. NaikNicholas M. Pajewski, Carmen A. Peralta, Adrienne Tin, Christina L. Wassel, James G. Wilson, Cheryl A. Winkler, Bessie A. Young, Neil A. Zakai, Barry I. Freedman

Research output: Contribution to journalArticle

Abstract

Background 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, butwhether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results. MethodsWe 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. Results 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. Conclusions 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.

Original languageEnglish (US)
Pages (from-to)2027-2036
Number of pages10
JournalJournal of the American Society of Nephrology
Volume30
Issue number10
DOIs
StatePublished - Jan 1 2019

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Meta-Analysis
Cardiovascular Diseases
Kidney
Genes
Heart Failure
Kidney Diseases
Coronary Disease
Stroke
Myocardial Infarction
Genotype
Body Mass Index
Confidence Intervals

ASJC Scopus subject areas

  • Nephrology

Cite this

APOL1 kidney risk variants and cardiovascular disease : An individual participant data meta-analysis. / Grams, Morgan E.; Surapaneni, Aditya; Ballew, Shoshana H.; Appel, Lawrence J.; Boerwinkle, Eric; Boulware, L. Ebony; Chen, Teresa K.; Coresh, Josef; Cushman, Mary; Divers, Jasmin; Gutiérrez, Orlando M.; Irvin, Marguerite R.; Ix, Joachim H.; Kopp, Jeffrey B.; Kuller, Lewis H.; Langefeld, Carl D.; Lipkowitz, Michael S.; Mukamal, Kenneth J.; Musani, Solomon K.; Naik, Rakhi P.; Pajewski, Nicholas M.; Peralta, Carmen A.; Tin, Adrienne; Wassel, Christina L.; Wilson, James G.; Winkler, Cheryl A.; Young, Bessie A.; Zakai, Neil A.; Freedman, Barry I.

In: Journal of the American Society of Nephrology, Vol. 30, No. 10, 01.01.2019, p. 2027-2036.

Research output: Contribution to journalArticle

Grams, ME, Surapaneni, A, Ballew, SH, Appel, LJ, Boerwinkle, E, Boulware, LE, Chen, TK, Coresh, J, Cushman, M, Divers, J, Gutiérrez, OM, Irvin, MR, Ix, JH, Kopp, JB, Kuller, LH, Langefeld, CD, Lipkowitz, MS, Mukamal, KJ, Musani, SK, Naik, RP, Pajewski, NM, Peralta, CA, Tin, A, Wassel, CL, Wilson, JG, Winkler, CA, Young, BA, Zakai, NA & Freedman, BI 2019, 'APOL1 kidney risk variants and cardiovascular disease: An individual participant data meta-analysis', Journal of the American Society of Nephrology, vol. 30, no. 10, pp. 2027-2036. https://doi.org/10.1681/ASN.2019030240
Grams, Morgan E. ; Surapaneni, Aditya ; Ballew, Shoshana H. ; Appel, Lawrence J. ; Boerwinkle, Eric ; Boulware, L. Ebony ; Chen, Teresa K. ; Coresh, Josef ; Cushman, Mary ; Divers, Jasmin ; Gutiérrez, Orlando M. ; Irvin, Marguerite R. ; Ix, Joachim H. ; Kopp, Jeffrey B. ; Kuller, Lewis H. ; Langefeld, Carl D. ; Lipkowitz, Michael S. ; Mukamal, Kenneth J. ; Musani, Solomon K. ; Naik, Rakhi P. ; Pajewski, Nicholas M. ; Peralta, Carmen A. ; Tin, Adrienne ; Wassel, Christina L. ; Wilson, James G. ; Winkler, Cheryl A. ; Young, Bessie A. ; Zakai, Neil A. ; Freedman, Barry I. / APOL1 kidney risk variants and cardiovascular disease : An individual participant data meta-analysis. In: Journal of the American Society of Nephrology. 2019 ; Vol. 30, No. 10. pp. 2027-2036.
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abstract = "Background 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, butwhether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results. MethodsWe 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. Results 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. Conclusions 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.",
author = "Grams, {Morgan E.} and Aditya Surapaneni and Ballew, {Shoshana H.} and Appel, {Lawrence J.} and Eric Boerwinkle and Boulware, {L. Ebony} and Chen, {Teresa K.} and Josef Coresh and Mary Cushman and Jasmin Divers and Guti{\'e}rrez, {Orlando M.} and Irvin, {Marguerite R.} and Ix, {Joachim H.} and Kopp, {Jeffrey B.} and Kuller, {Lewis H.} and Langefeld, {Carl D.} and Lipkowitz, {Michael S.} and Mukamal, {Kenneth J.} and Musani, {Solomon K.} and Naik, {Rakhi P.} and Pajewski, {Nicholas M.} and Peralta, {Carmen A.} and Adrienne Tin and Wassel, {Christina L.} and Wilson, {James G.} and Winkler, {Cheryl A.} and Young, {Bessie A.} and Zakai, {Neil A.} and Freedman, {Barry I.}",
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T1 - APOL1 kidney risk variants and cardiovascular disease

T2 - An individual participant data meta-analysis

AU - Grams, Morgan E.

AU - Surapaneni, Aditya

AU - Ballew, Shoshana H.

AU - Appel, Lawrence J.

AU - Boerwinkle, Eric

AU - Boulware, L. Ebony

AU - Chen, Teresa K.

AU - Coresh, Josef

AU - Cushman, Mary

AU - Divers, Jasmin

AU - Gutiérrez, Orlando M.

AU - Irvin, Marguerite R.

AU - Ix, Joachim H.

AU - Kopp, Jeffrey B.

AU - Kuller, Lewis H.

AU - Langefeld, Carl D.

AU - Lipkowitz, Michael S.

AU - Mukamal, Kenneth J.

AU - Musani, Solomon K.

AU - Naik, Rakhi P.

AU - Pajewski, Nicholas M.

AU - Peralta, Carmen A.

AU - Tin, Adrienne

AU - Wassel, Christina L.

AU - Wilson, James G.

AU - Winkler, Cheryl A.

AU - Young, Bessie A.

AU - Zakai, Neil A.

AU - Freedman, Barry I.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background 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, butwhether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results. MethodsWe 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. Results 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. Conclusions 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.

AB - Background 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, butwhether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results. MethodsWe 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. Results 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. Conclusions 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.

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