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 - 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.
UR - http://www.scopus.com/inward/record.url?scp=85062594771&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062594771&partnerID=8YFLogxK
U2 - 10.1155/2019/2137629
DO - 10.1155/2019/2137629
M3 - Article
AN - SCOPUS:85062594771
SN - 2090-0384
VL - 2019
JO - International Journal of Hypertension
JF - International Journal of Hypertension
M1 - 2137629
ER -