TY - JOUR
T1 - Association of FMO3 Variants with Blood Pressure in the Atherosclerosis Risk in Communities Study
AU - Bryant, Tyler S.
AU - Duggal, Priya
AU - Yu, Bing
AU - Morrison, Alanna C.
AU - Shafi, Tariq
AU - Ehret, Georg
AU - Franceschini, Nora
AU - Boerwinkle, Eric
AU - Coresh, Josef
AU - Tin, Adrienne
N1 - Funding Information:
Funding support for “Building on GWAS for NHLBI-diseases: the U.S. CHARGE consortium” was provided by the NIH through the American Recovery and Reinvestment Act of 2009 (ARRA) (5RC2HL102419). Data for “Building on GWAS for NHLBI-diseases: the U.S. CHARGE consortium” was provided by Eric Boerwinkle on behalf of the Atherosclerosis Risk in Communities (ARIC) Study, L. Adrienne Cupples, principal investigator for the Fram-ingham Heart Study, and Bruce Psaty, principal investigator for the Cardiovascular Health Study. Sequencing was carried out at the Baylor College of Medicine Human Genome Sequencing Center and supported by the National Human Genome Research Institute Grants U54 HG003273 and UM1 HG008898. The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal Funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (Contracts nos. HHSN268201700001I, HHSN268201700002I, HHSN268201-700003I, HHSN268201700004I, and HHSN268201700005I). The authors thank the staff and participants of the ARIC study for their important contributions. The Framing-ham Heart Study is conducted and supported by the NHLBI in collaboration with Boston University (Contract no. N01-HC-25195) and its contract with Affymetrix, Inc., for genome-wide genotyping services (Contract no. N02-HL-6-4278), for quality control by Framingham Heart Study investigators using genotypes in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA) computing resources at Boston University Medical Campus. This CHS research was supported by Contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and Grants HL080295, HL087652, and HL105756 from the National Heart, Lung, and Blood Institute (NHLBI) with additional contribution from National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG023629 from the National Institutes on Aging (NIA). A full list of CHS principal investigators and institutions can be found at CHS-NHLBI.org.
Publisher Copyright:
© 2019 Tyler S. Bryant et al.
PY - 2019
Y1 - 2019
N2 - Flavin containing monooxygenase 3 [FMO3] encodes dimethylaniline monooxygenase [N-oxide-forming] 3, which breaks down nitrogen-containing compounds, and has been implicated in blood pressure regulation. Studies have reported conflicting results of the association of a common nonsynonymous variant, E158K (rs2266782), with hypertension. We examined the associations of E158K, along with rare and low frequency exonic variants (minor allele frequency [MAF]<5%) in FMO3 with hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP). We included 7,350 European Americans and 2,814 African Americans in the Atherosclerosis Risk in Communities (ARIC) study with exome sequencing of FMO3. The association of FMO3 variants with SBP and DBP was tested using single variant and gene-based tests followed by the replication or interrogation of significant variants in ancestry-specific cohorts based on Bonferroni corrected thresholds. E158K had significant association with higher SBP in African Americans in ARIC (p=0.03), and two low frequency variants had significant association with higher SBP in African Americans (rs200985584, MAF 0.1%, p=0.0003) and European Americans (rs75904274, MAF 1.7%, p=0.006). These associations were not significant with additional samples: E158K in a meta-Analysis of SBP of African ancestry (N=30,841, p=0.43) that included ARIC participants and the two low frequency variants in an independent ancestry-specific exome sequencing study of blood pressure (rs200985584, p=0.94; rs75904274, p=0.81). Our study does not support the association of E158K and low frequency variants in FMO3 with blood pressure and demonstrates the importance of replication in genetic studies.
AB - Flavin containing monooxygenase 3 [FMO3] encodes dimethylaniline monooxygenase [N-oxide-forming] 3, which breaks down nitrogen-containing compounds, and has been implicated in blood pressure regulation. Studies have reported conflicting results of the association of a common nonsynonymous variant, E158K (rs2266782), with hypertension. We examined the associations of E158K, along with rare and low frequency exonic variants (minor allele frequency [MAF]<5%) in FMO3 with hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP). We included 7,350 European Americans and 2,814 African Americans in the Atherosclerosis Risk in Communities (ARIC) study with exome sequencing of FMO3. The association of FMO3 variants with SBP and DBP was tested using single variant and gene-based tests followed by the replication or interrogation of significant variants in ancestry-specific cohorts based on Bonferroni corrected thresholds. E158K had significant association with higher SBP in African Americans in ARIC (p=0.03), and two low frequency variants had significant association with higher SBP in African Americans (rs200985584, MAF 0.1%, p=0.0003) and European Americans (rs75904274, MAF 1.7%, p=0.006). These associations were not significant with additional samples: E158K in a meta-Analysis of SBP of African ancestry (N=30,841, p=0.43) that included ARIC participants and the two low frequency variants in an independent ancestry-specific exome sequencing study of blood pressure (rs200985584, p=0.94; rs75904274, p=0.81). Our study does not support the association of E158K and low frequency variants in FMO3 with blood pressure and demonstrates the importance of replication in genetic studies.
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U2 - 10.1155/2019/2137629
DO - 10.1155/2019/2137629
M3 - Article
C2 - 30906589
AN - SCOPUS:85062594771
SN - 2090-0384
VL - 2019
JO - International Journal of Hypertension
JF - International Journal of Hypertension
M1 - 2137629
ER -