Genome-Wide Gene-Potassium Interaction Analyses on Blood Pressure: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity)

Changwei Li; Jiang He; Jing Chen; Jinying Zhao; Dongfeng Gu; James E. Hixson; Dabeeru C. Rao; Cashell E. Jaquish; Treva K. Rice; Yun Ju Sung; Tanika N. Kelly

doi:10.1161/CIRCGENETICS.117.001811

Genome-Wide Gene-Potassium Interaction Analyses on Blood Pressure: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity)

Changwei Li, Jiang He, Jing Chen, Jinying Zhao, Dongfeng Gu, James E. Hixson, Dabeeru C. Rao, Cashell E. Jaquish, Treva K. Rice, Yun Ju Sung, Tanika N. Kelly

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Abstract

Background - Gene-environmental interaction analysis can identify novel genetic factors for blood pressure (BP). We performed genome-wide analyses to identify genomic loci that interact with potassium to influence BP using single-marker (1 and 2 df joint tests) and gene-based tests among Chinese participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity). Methods and Results - Among 1876 GenSalt participants, the average of 3 urine samples was used to estimate potassium excretion. Nine BP measurements were taken using a random-zero sphygmomanometer. A total of 2.2 million single nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (P<1.00×10^-⁴) from GenSalt were evaluated for replication among 775 Chinese participants of the MESA (Multi-ethnic Study of Atherosclerosis). Single nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1 df tests identified interactions for ARL15 rs16882447 on systolic BP (P=2.83×10^-9) and RANBP3L rs958929 on pulse pressure (P=1.58×10^-8). The 2 df tests confirmed the ARL15 rs16882447 signal for systolic BP (P=1.15×10^-9). Genome-wide gene-based analysis identified CC2D2A (P=2.59×10^-7) at 4p15.32 and BNC2 (P=4.49×10^-¹⁰) at 9p22.2 for systolic BP, GGNBP1 (P=1.18×10^-⁸), and LINC00336 (P=1.36×10^-⁸) at 6p21 for diastolic BP, DAB1 (P=1.05×10^-¹³) at 1p32.2, and MIR4466 (P=5.34×10^-⁸) at 6q25.3 for pulse pressure. The BNC2 (P=3.57×10^-⁸) gene was also significant for mean arterial pressure. Conclusions - We identified 2 novel BP loci and 6 genes through the examination of single nucleotide polymorphism- and gene-based interactions with potassium.

Original language	English
Article number	e001811
Journal	Circulation: Cardiovascular Genetics
Volume	10
Issue number	6
DOIs	https://doi.org/10.1161/CIRCGENETICS.117.001811
State	Published - Dec 1 2017

Keywords

blood pressure
genome-wide association study
genotype
potassium

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10.1161/CIRCGENETICS.117.001811

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Li, C., He, J., Chen, J., Zhao, J., Gu, D., Hixson, J. E., Rao, D. C., Jaquish, C. E., Rice, T. K., Sung, Y. J., & Kelly, T. N. (2017). Genome-Wide Gene-Potassium Interaction Analyses on Blood Pressure: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity). Circulation: Cardiovascular Genetics, 10(6), Article e001811. https://doi.org/10.1161/CIRCGENETICS.117.001811

@article{04581cd8c49848ec8d6d94120a42304b,

title = "Genome-Wide Gene-Potassium Interaction Analyses on Blood Pressure: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity)",

abstract = "Background - Gene-environmental interaction analysis can identify novel genetic factors for blood pressure (BP). We performed genome-wide analyses to identify genomic loci that interact with potassium to influence BP using single-marker (1 and 2 df joint tests) and gene-based tests among Chinese participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity). Methods and Results - Among 1876 GenSalt participants, the average of 3 urine samples was used to estimate potassium excretion. Nine BP measurements were taken using a random-zero sphygmomanometer. A total of 2.2 million single nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (P<1.00×10-4) from GenSalt were evaluated for replication among 775 Chinese participants of the MESA (Multi-ethnic Study of Atherosclerosis). Single nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1 df tests identified interactions for ARL15 rs16882447 on systolic BP (P=2.83×10-9) and RANBP3L rs958929 on pulse pressure (P=1.58×10-8). The 2 df tests confirmed the ARL15 rs16882447 signal for systolic BP (P=1.15×10-9). Genome-wide gene-based analysis identified CC2D2A (P=2.59×10-7) at 4p15.32 and BNC2 (P=4.49×10-10) at 9p22.2 for systolic BP, GGNBP1 (P=1.18×10-8), and LINC00336 (P=1.36×10-8) at 6p21 for diastolic BP, DAB1 (P=1.05×10-13) at 1p32.2, and MIR4466 (P=5.34×10-8) at 6q25.3 for pulse pressure. The BNC2 (P=3.57×10-8) gene was also significant for mean arterial pressure. Conclusions - We identified 2 novel BP loci and 6 genes through the examination of single nucleotide polymorphism- and gene-based interactions with potassium.",

keywords = "blood pressure, genome-wide association study, genotype, potassium",

author = "Changwei Li and Jiang He and Jing Chen and Jinying Zhao and Dongfeng Gu and Hixson, {James E.} and Rao, {Dabeeru C.} and Jaquish, {Cashell E.} and Rice, {Treva K.} and Sung, {Yun Ju} and Kelly, {Tanika N.}",

note = "Publisher Copyright: {\textcopyright} 2017 American Heart Association, Inc.",

year = "2017",

month = dec,

day = "1",

doi = "10.1161/CIRCGENETICS.117.001811",

language = "English",

volume = "10",

journal = "Circulation: Cardiovascular Genetics",

issn = "1942-325X",

number = "6",

}

TY - JOUR

T1 - Genome-Wide Gene-Potassium Interaction Analyses on Blood Pressure

T2 - The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity)

AU - Li, Changwei

AU - He, Jiang

AU - Chen, Jing

AU - Zhao, Jinying

AU - Gu, Dongfeng

AU - Hixson, James E.

AU - Rao, Dabeeru C.

AU - Jaquish, Cashell E.

AU - Rice, Treva K.

AU - Sung, Yun Ju

AU - Kelly, Tanika N.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Background - Gene-environmental interaction analysis can identify novel genetic factors for blood pressure (BP). We performed genome-wide analyses to identify genomic loci that interact with potassium to influence BP using single-marker (1 and 2 df joint tests) and gene-based tests among Chinese participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity). Methods and Results - Among 1876 GenSalt participants, the average of 3 urine samples was used to estimate potassium excretion. Nine BP measurements were taken using a random-zero sphygmomanometer. A total of 2.2 million single nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (P<1.00×10-4) from GenSalt were evaluated for replication among 775 Chinese participants of the MESA (Multi-ethnic Study of Atherosclerosis). Single nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1 df tests identified interactions for ARL15 rs16882447 on systolic BP (P=2.83×10-9) and RANBP3L rs958929 on pulse pressure (P=1.58×10-8). The 2 df tests confirmed the ARL15 rs16882447 signal for systolic BP (P=1.15×10-9). Genome-wide gene-based analysis identified CC2D2A (P=2.59×10-7) at 4p15.32 and BNC2 (P=4.49×10-10) at 9p22.2 for systolic BP, GGNBP1 (P=1.18×10-8), and LINC00336 (P=1.36×10-8) at 6p21 for diastolic BP, DAB1 (P=1.05×10-13) at 1p32.2, and MIR4466 (P=5.34×10-8) at 6q25.3 for pulse pressure. The BNC2 (P=3.57×10-8) gene was also significant for mean arterial pressure. Conclusions - We identified 2 novel BP loci and 6 genes through the examination of single nucleotide polymorphism- and gene-based interactions with potassium.

AB - Background - Gene-environmental interaction analysis can identify novel genetic factors for blood pressure (BP). We performed genome-wide analyses to identify genomic loci that interact with potassium to influence BP using single-marker (1 and 2 df joint tests) and gene-based tests among Chinese participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity). Methods and Results - Among 1876 GenSalt participants, the average of 3 urine samples was used to estimate potassium excretion. Nine BP measurements were taken using a random-zero sphygmomanometer. A total of 2.2 million single nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (P<1.00×10-4) from GenSalt were evaluated for replication among 775 Chinese participants of the MESA (Multi-ethnic Study of Atherosclerosis). Single nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1 df tests identified interactions for ARL15 rs16882447 on systolic BP (P=2.83×10-9) and RANBP3L rs958929 on pulse pressure (P=1.58×10-8). The 2 df tests confirmed the ARL15 rs16882447 signal for systolic BP (P=1.15×10-9). Genome-wide gene-based analysis identified CC2D2A (P=2.59×10-7) at 4p15.32 and BNC2 (P=4.49×10-10) at 9p22.2 for systolic BP, GGNBP1 (P=1.18×10-8), and LINC00336 (P=1.36×10-8) at 6p21 for diastolic BP, DAB1 (P=1.05×10-13) at 1p32.2, and MIR4466 (P=5.34×10-8) at 6q25.3 for pulse pressure. The BNC2 (P=3.57×10-8) gene was also significant for mean arterial pressure. Conclusions - We identified 2 novel BP loci and 6 genes through the examination of single nucleotide polymorphism- and gene-based interactions with potassium.

KW - blood pressure

KW - genome-wide association study

KW - genotype

KW - potassium

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U2 - 10.1161/CIRCGENETICS.117.001811

DO - 10.1161/CIRCGENETICS.117.001811

M3 - Article

C2 - 29212900

AN - SCOPUS:85038630011

SN - 1942-325X

VL - 10

JO - Circulation: Cardiovascular Genetics

JF - Circulation: Cardiovascular Genetics

IS - 6

M1 - e001811

ER -

Genome-Wide Gene-Potassium Interaction Analyses on Blood Pressure: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity)

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