Heterogeneous effects of association between blood pressure loci and coronary artery disease in east asian individuals

AGEN Consortium

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Abstract

Background: A coronary artery disease (CAD) association study of genetic loci previously identified as being associated with blood pressure (BP) was performed in east Asian populations. Methods and Results: Nine single nucleotide polymorphisms (SNPs) from 9 candidate loci robustly confirmed to be associated with BP in east Asian people, were genotyped. Genotyping was done in up to 17,785 CAD casecontrol samples (6,522 cases and 11,263 controls). We then tested the associations with other metabolic traits (n≤17,900) and with type 2 diabetes (931 cases and 1,404 controls), and looked up the datasets in silico in other populations. Significant (adjusted P<0.05) CAD associations were found for 5 BP loci: 3 new CAD associations at FIGN, FGF5 and NPR3, and 2 previously reported ones at ATP2B1 and CNNM2. The strongest CAD association was detected at ATP2B1 rs2681472 (P=1.7×10–8), in the direction inverted to what is generally recognized for BP in the epidemiological studies. CNNM2 rs12413409 showed significant association with CAD (P=8.7×10–7) and BMI (P=3.5×10–8, when meta-analyzed with 75,807 east Asian people). The genetic risk score combining BP-raising alleles at each of the SNPs was positively associated with CAD (P=0.011). Conclusions: A substantial proportion of genetic variants associated with BP were also associated with the risk of CAD in east Asian people, and there was some counter-evidence for causal inference.

Original languageEnglish
Pages (from-to)830-838
Number of pages9
JournalCirculation Journal
Volume79
Issue number4
DOIs
Publication statusPublished - 2015 Jan 1

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Coronary Artery Disease
Blood Pressure
Single Nucleotide Polymorphism
Genetic Loci
Computer Simulation
Type 2 Diabetes Mellitus
Population
Epidemiologic Studies
Alleles

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

@article{d2921fe4eb894980a08df87b6310f4c9,
title = "Heterogeneous effects of association between blood pressure loci and coronary artery disease in east asian individuals",
abstract = "Background: A coronary artery disease (CAD) association study of genetic loci previously identified as being associated with blood pressure (BP) was performed in east Asian populations. Methods and Results: Nine single nucleotide polymorphisms (SNPs) from 9 candidate loci robustly confirmed to be associated with BP in east Asian people, were genotyped. Genotyping was done in up to 17,785 CAD casecontrol samples (6,522 cases and 11,263 controls). We then tested the associations with other metabolic traits (n≤17,900) and with type 2 diabetes (931 cases and 1,404 controls), and looked up the datasets in silico in other populations. Significant (adjusted P<0.05) CAD associations were found for 5 BP loci: 3 new CAD associations at FIGN, FGF5 and NPR3, and 2 previously reported ones at ATP2B1 and CNNM2. The strongest CAD association was detected at ATP2B1 rs2681472 (P=1.7×10–8), in the direction inverted to what is generally recognized for BP in the epidemiological studies. CNNM2 rs12413409 showed significant association with CAD (P=8.7×10–7) and BMI (P=3.5×10–8, when meta-analyzed with 75,807 east Asian people). The genetic risk score combining BP-raising alleles at each of the SNPs was positively associated with CAD (P=0.011). Conclusions: A substantial proportion of genetic variants associated with BP were also associated with the risk of CAD in east Asian people, and there was some counter-evidence for causal inference.",
author = "{AGEN Consortium} and Fumihiko Takeuchi and Masato Isono and Ken Yamamoto and Mitsuhiro Yokota and Koichi Akiyama and Tomohiro Katsuya and Kim, {Hyo Soo} and Park, {Jeong Euy} and Yangsoo Jang and Lee, {Ji Young} and Lee, {Jong Young} and Norihiro Kato",
year = "2015",
month = "1",
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doi = "10.1253/circj.CJ-14-0841",
language = "English",
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Heterogeneous effects of association between blood pressure loci and coronary artery disease in east asian individuals. / AGEN Consortium.

In: Circulation Journal, Vol. 79, No. 4, 01.01.2015, p. 830-838.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Heterogeneous effects of association between blood pressure loci and coronary artery disease in east asian individuals

AU - AGEN Consortium

AU - Takeuchi, Fumihiko

AU - Isono, Masato

AU - Yamamoto, Ken

AU - Yokota, Mitsuhiro

AU - Akiyama, Koichi

AU - Katsuya, Tomohiro

AU - Kim, Hyo Soo

AU - Park, Jeong Euy

AU - Jang, Yangsoo

AU - Lee, Ji Young

AU - Lee, Jong Young

AU - Kato, Norihiro

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background: A coronary artery disease (CAD) association study of genetic loci previously identified as being associated with blood pressure (BP) was performed in east Asian populations. Methods and Results: Nine single nucleotide polymorphisms (SNPs) from 9 candidate loci robustly confirmed to be associated with BP in east Asian people, were genotyped. Genotyping was done in up to 17,785 CAD casecontrol samples (6,522 cases and 11,263 controls). We then tested the associations with other metabolic traits (n≤17,900) and with type 2 diabetes (931 cases and 1,404 controls), and looked up the datasets in silico in other populations. Significant (adjusted P<0.05) CAD associations were found for 5 BP loci: 3 new CAD associations at FIGN, FGF5 and NPR3, and 2 previously reported ones at ATP2B1 and CNNM2. The strongest CAD association was detected at ATP2B1 rs2681472 (P=1.7×10–8), in the direction inverted to what is generally recognized for BP in the epidemiological studies. CNNM2 rs12413409 showed significant association with CAD (P=8.7×10–7) and BMI (P=3.5×10–8, when meta-analyzed with 75,807 east Asian people). The genetic risk score combining BP-raising alleles at each of the SNPs was positively associated with CAD (P=0.011). Conclusions: A substantial proportion of genetic variants associated with BP were also associated with the risk of CAD in east Asian people, and there was some counter-evidence for causal inference.

AB - Background: A coronary artery disease (CAD) association study of genetic loci previously identified as being associated with blood pressure (BP) was performed in east Asian populations. Methods and Results: Nine single nucleotide polymorphisms (SNPs) from 9 candidate loci robustly confirmed to be associated with BP in east Asian people, were genotyped. Genotyping was done in up to 17,785 CAD casecontrol samples (6,522 cases and 11,263 controls). We then tested the associations with other metabolic traits (n≤17,900) and with type 2 diabetes (931 cases and 1,404 controls), and looked up the datasets in silico in other populations. Significant (adjusted P<0.05) CAD associations were found for 5 BP loci: 3 new CAD associations at FIGN, FGF5 and NPR3, and 2 previously reported ones at ATP2B1 and CNNM2. The strongest CAD association was detected at ATP2B1 rs2681472 (P=1.7×10–8), in the direction inverted to what is generally recognized for BP in the epidemiological studies. CNNM2 rs12413409 showed significant association with CAD (P=8.7×10–7) and BMI (P=3.5×10–8, when meta-analyzed with 75,807 east Asian people). The genetic risk score combining BP-raising alleles at each of the SNPs was positively associated with CAD (P=0.011). Conclusions: A substantial proportion of genetic variants associated with BP were also associated with the risk of CAD in east Asian people, and there was some counter-evidence for causal inference.

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U2 - 10.1253/circj.CJ-14-0841

DO - 10.1253/circj.CJ-14-0841

M3 - Article

C2 - 25740055

AN - SCOPUS:84925597017

VL - 79

SP - 830

EP - 838

JO - Circulation Journal

JF - Circulation Journal

SN - 1346-9843

IS - 4

ER -