Apolipoprotein L1 Variants and Blood Pressure Traits in African Americans

Girish N. Nadkarni, Geneviève Galarneau, Stephen B. Ellis, Rajiv Nadukuru, Jinglan Zhang, Stuart A. Scott, Claudia Schurmann, Rongling Li, Laura J. Rasmussen-Torvik, Abel N. Kho, M. Geoffrey Hayes, Jennifer A. Pacheco, Teri A. Manolio, Rex L. Chisholm, Dan M. Roden, Joshua C. Denny, Eimear E. Kenny, Erwin P. Bottinger

Research output: Contribution to journalArticle

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Abstract

Background African Americans (AA) are disproportionately affected by hypertension-related health disparities. Apolipoprotein L1 (APOL1) risk variants are associated with kidney disease in hypertensive AAs. Objectives This study assessed the APOL1 risk alleles’ association with blood pressure traits in AAs. Methods The discovery cohort included 5,204 AA participants from Mount Sinai's BioMe biobank. Replication cohorts included additional BioMe (n = 1,623), Vanderbilt BioVU (n = 1,809), and Northwestern NUgene (n = 567) AA biobank participants. Single nucleotide polymorphisms determining APOL1 G1 and G2 risk alleles were genotyped in BioMe and imputed in BioVU/NUgene participants. APOL1 risk alleles’ association with blood pressure–related traits was tested in the discovery cohort, a meta-analysis of replication cohorts, and a combined meta-analysis under recessive and additive models after adjusting for age, sex, body mass index, and estimated glomerular filtration rate. Results There were 14% to 16% of APOL1 variant allele homozygotes (2 copies of G1/G2) across cohorts. APOL1 risk alleles were associated under an additive model with systolic blood pressure (SBP) and age at diagnosis of hypertension, which was 2 to 5 years younger in the APOL1 variant allele homozygotes (Cox proportional hazards analysis, p value for combined meta-analysis [pcom] = 1.9 × 10−5). APOL1 risk alleles were associated with overall SBP (pcom = 7.0 × 10−8) and diastolic blood pressure (pcom = 2.8 × 10−4). After adjustment for all covariates, those in the 20- to 29-year age range showed an increase in SBP of 0.94 ± 0.44 mm Hg (pcom = 0.01) per risk variant copy. APOL1-associated estimated glomerular filtration rate decline was observed starting a decade later in life in the 30- to 39-year age range. Conclusions APOL1 risk alleles are associated with higher SBP and earlier hypertension diagnoses in young AAs; this relationship appears to follow an additive model.

LanguageEnglish (US)
Pages1564-1574
Number of pages11
JournalJournal of the American College of Cardiology
Volume69
Issue number12
DOIs
StatePublished - Mar 28 2017

Fingerprint

Apolipoproteins
African Americans
Blood Pressure
Alleles
Hypertension
Ecosystem
Meta-Analysis
Homozygote
Glomerular Filtration Rate
Kidney Diseases
Single Nucleotide Polymorphism
Early Diagnosis
Body Mass Index

Keywords

  • allele
  • APOL1
  • estimated glomerular filtration rate
  • genetic association studies
  • kidney disease

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Nadkarni, G. N., Galarneau, G., Ellis, S. B., Nadukuru, R., Zhang, J., Scott, S. A., ... Bottinger, E. P. (2017). Apolipoprotein L1 Variants and Blood Pressure Traits in African Americans. Journal of the American College of Cardiology, 69(12), 1564-1574. DOI: 10.1016/j.jacc.2017.01.040
Nadkarni, Girish N. ; Galarneau, Geneviève ; Ellis, Stephen B. ; Nadukuru, Rajiv ; Zhang, Jinglan ; Scott, Stuart A. ; Schurmann, Claudia ; Li, Rongling ; Rasmussen-Torvik, Laura J. ; Kho, Abel N. ; Hayes, M. Geoffrey ; Pacheco, Jennifer A. ; Manolio, Teri A. ; Chisholm, Rex L. ; Roden, Dan M. ; Denny, Joshua C. ; Kenny, Eimear E. ; Bottinger, Erwin P./ Apolipoprotein L1 Variants and Blood Pressure Traits in African Americans. In: Journal of the American College of Cardiology. 2017 ; Vol. 69, No. 12. pp. 1564-1574
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abstract = "Background African Americans (AA) are disproportionately affected by hypertension-related health disparities. Apolipoprotein L1 (APOL1) risk variants are associated with kidney disease in hypertensive AAs. Objectives This study assessed the APOL1 risk alleles’ association with blood pressure traits in AAs. Methods The discovery cohort included 5,204 AA participants from Mount Sinai's BioMe biobank. Replication cohorts included additional BioMe (n = 1,623), Vanderbilt BioVU (n = 1,809), and Northwestern NUgene (n = 567) AA biobank participants. Single nucleotide polymorphisms determining APOL1 G1 and G2 risk alleles were genotyped in BioMe and imputed in BioVU/NUgene participants. APOL1 risk alleles’ association with blood pressure–related traits was tested in the discovery cohort, a meta-analysis of replication cohorts, and a combined meta-analysis under recessive and additive models after adjusting for age, sex, body mass index, and estimated glomerular filtration rate. Results There were 14\{%} to 16\{%} of APOL1 variant allele homozygotes (2 copies of G1/G2) across cohorts. APOL1 risk alleles were associated under an additive model with systolic blood pressure (SBP) and age at diagnosis of hypertension, which was 2 to 5 years younger in the APOL1 variant allele homozygotes (Cox proportional hazards analysis, p value for combined meta-analysis [pcom] = 1.9 × 10−5). APOL1 risk alleles were associated with overall SBP (pcom = 7.0 × 10−8) and diastolic blood pressure (pcom = 2.8 × 10−4). After adjustment for all covariates, those in the 20- to 29-year age range showed an increase in SBP of 0.94 ± 0.44 mm Hg (pcom = 0.01) per risk variant copy. APOL1-associated estimated glomerular filtration rate decline was observed starting a decade later in life in the 30- to 39-year age range. Conclusions APOL1 risk alleles are associated with higher SBP and earlier hypertension diagnoses in young AAs; this relationship appears to follow an additive model.",
keywords = "allele, APOL1, estimated glomerular filtration rate, genetic association studies, kidney disease",
author = "Nadkarni, {Girish N.} and Genevi\{`e}ve Galarneau and Ellis, {Stephen B.} and Rajiv Nadukuru and Jinglan Zhang and Scott, {Stuart A.} and Claudia Schurmann and Rongling Li and Rasmussen-Torvik, {Laura J.} and Kho, {Abel N.} and Hayes, {M. Geoffrey} and Pacheco, {Jennifer A.} and Manolio, {Teri A.} and Chisholm, {Rex L.} and Roden, {Dan M.} and Denny, {Joshua C.} and Kenny, {Eimear E.} and Bottinger, {Erwin P.}",
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Nadkarni, GN, Galarneau, G, Ellis, SB, Nadukuru, R, Zhang, J, Scott, SA, Schurmann, C, Li, R, Rasmussen-Torvik, LJ, Kho, AN, Hayes, MG, Pacheco, JA, Manolio, TA, Chisholm, RL, Roden, DM, Denny, JC, Kenny, EE & Bottinger, EP 2017, 'Apolipoprotein L1 Variants and Blood Pressure Traits in African Americans' Journal of the American College of Cardiology, vol 69, no. 12, pp. 1564-1574. DOI: 10.1016/j.jacc.2017.01.040

Apolipoprotein L1 Variants and Blood Pressure Traits in African Americans. / Nadkarni, Girish N.; Galarneau, Geneviève; Ellis, Stephen B.; Nadukuru, Rajiv; Zhang, Jinglan; Scott, Stuart A.; Schurmann, Claudia; Li, Rongling; Rasmussen-Torvik, Laura J.; Kho, Abel N.; Hayes, M. Geoffrey; Pacheco, Jennifer A.; Manolio, Teri A.; Chisholm, Rex L.; Roden, Dan M.; Denny, Joshua C.; Kenny, Eimear E.; Bottinger, Erwin P.

In: Journal of the American College of Cardiology, Vol. 69, No. 12, 28.03.2017, p. 1564-1574.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Apolipoprotein L1 Variants and Blood Pressure Traits in African Americans

AU - Nadkarni,Girish N.

AU - Galarneau,Geneviève

AU - Ellis,Stephen B.

AU - Nadukuru,Rajiv

AU - Zhang,Jinglan

AU - Scott,Stuart A.

AU - Schurmann,Claudia

AU - Li,Rongling

AU - Rasmussen-Torvik,Laura J.

AU - Kho,Abel N.

AU - Hayes,M. Geoffrey

AU - Pacheco,Jennifer A.

AU - Manolio,Teri A.

AU - Chisholm,Rex L.

AU - Roden,Dan M.

AU - Denny,Joshua C.

AU - Kenny,Eimear E.

AU - Bottinger,Erwin P.

PY - 2017/3/28

Y1 - 2017/3/28

N2 - Background African Americans (AA) are disproportionately affected by hypertension-related health disparities. Apolipoprotein L1 (APOL1) risk variants are associated with kidney disease in hypertensive AAs. Objectives This study assessed the APOL1 risk alleles’ association with blood pressure traits in AAs. Methods The discovery cohort included 5,204 AA participants from Mount Sinai's BioMe biobank. Replication cohorts included additional BioMe (n = 1,623), Vanderbilt BioVU (n = 1,809), and Northwestern NUgene (n = 567) AA biobank participants. Single nucleotide polymorphisms determining APOL1 G1 and G2 risk alleles were genotyped in BioMe and imputed in BioVU/NUgene participants. APOL1 risk alleles’ association with blood pressure–related traits was tested in the discovery cohort, a meta-analysis of replication cohorts, and a combined meta-analysis under recessive and additive models after adjusting for age, sex, body mass index, and estimated glomerular filtration rate. Results There were 14% to 16% of APOL1 variant allele homozygotes (2 copies of G1/G2) across cohorts. APOL1 risk alleles were associated under an additive model with systolic blood pressure (SBP) and age at diagnosis of hypertension, which was 2 to 5 years younger in the APOL1 variant allele homozygotes (Cox proportional hazards analysis, p value for combined meta-analysis [pcom] = 1.9 × 10−5). APOL1 risk alleles were associated with overall SBP (pcom = 7.0 × 10−8) and diastolic blood pressure (pcom = 2.8 × 10−4). After adjustment for all covariates, those in the 20- to 29-year age range showed an increase in SBP of 0.94 ± 0.44 mm Hg (pcom = 0.01) per risk variant copy. APOL1-associated estimated glomerular filtration rate decline was observed starting a decade later in life in the 30- to 39-year age range. Conclusions APOL1 risk alleles are associated with higher SBP and earlier hypertension diagnoses in young AAs; this relationship appears to follow an additive model.

AB - Background African Americans (AA) are disproportionately affected by hypertension-related health disparities. Apolipoprotein L1 (APOL1) risk variants are associated with kidney disease in hypertensive AAs. Objectives This study assessed the APOL1 risk alleles’ association with blood pressure traits in AAs. Methods The discovery cohort included 5,204 AA participants from Mount Sinai's BioMe biobank. Replication cohorts included additional BioMe (n = 1,623), Vanderbilt BioVU (n = 1,809), and Northwestern NUgene (n = 567) AA biobank participants. Single nucleotide polymorphisms determining APOL1 G1 and G2 risk alleles were genotyped in BioMe and imputed in BioVU/NUgene participants. APOL1 risk alleles’ association with blood pressure–related traits was tested in the discovery cohort, a meta-analysis of replication cohorts, and a combined meta-analysis under recessive and additive models after adjusting for age, sex, body mass index, and estimated glomerular filtration rate. Results There were 14% to 16% of APOL1 variant allele homozygotes (2 copies of G1/G2) across cohorts. APOL1 risk alleles were associated under an additive model with systolic blood pressure (SBP) and age at diagnosis of hypertension, which was 2 to 5 years younger in the APOL1 variant allele homozygotes (Cox proportional hazards analysis, p value for combined meta-analysis [pcom] = 1.9 × 10−5). APOL1 risk alleles were associated with overall SBP (pcom = 7.0 × 10−8) and diastolic blood pressure (pcom = 2.8 × 10−4). After adjustment for all covariates, those in the 20- to 29-year age range showed an increase in SBP of 0.94 ± 0.44 mm Hg (pcom = 0.01) per risk variant copy. APOL1-associated estimated glomerular filtration rate decline was observed starting a decade later in life in the 30- to 39-year age range. Conclusions APOL1 risk alleles are associated with higher SBP and earlier hypertension diagnoses in young AAs; this relationship appears to follow an additive model.

KW - allele

KW - APOL1

KW - estimated glomerular filtration rate

KW - genetic association studies

KW - kidney disease

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Nadkarni GN, Galarneau G, Ellis SB, Nadukuru R, Zhang J, Scott SA et al. Apolipoprotein L1 Variants and Blood Pressure Traits in African Americans. Journal of the American College of Cardiology. 2017 Mar 28;69(12):1564-1574. Available from, DOI: 10.1016/j.jacc.2017.01.040