Identification of a genetic variant at 2q12.1 associated with blood pressure in East-Asians by genome-wide scan including gene-environment interactions

Yun K. Kim, Youngdoe Kim, Mi Y. Hwang, Kazuro Shimokawa, Sungho Won, Norihiro Kato, Yasuharu Tabara, Mitsuhiro Yokota, Bok Ghee Han, Jong Ho Lee, Bong Jo Kim

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Abstract

Background: Genome-wide association studies have identified many genetic loci associated with blood pressure (BP). Genetic effects on BP can be altered by environmental exposures via multiple biological pathways. Especially, obesity is one of important environmental risk factors that can have considerable effect on BP and it may interact with genetic factors. Given that, we aimed to test whether genetic factors and obesity may jointly influence BP.Methods: We performed meta-analyses of genome-wide association data for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that included analyses of interaction between single nucleotide polymorphisms (SNPs) and the obesity-related anthropometric measures, body mass index (BMI), height, weight, and waist/hip ratio (WHR) in East-Asians (n = 12,030).Results: We identified that rs13390641 on 2q12.1 demonstrated significant association with SBP when the interaction between SNPs and BMI was considered (P < 5 × 10 -8). The gene located nearest to rs13390641, TMEM182, encodes transmembrane protein 182. In stratified analyses, the effect of rs13390641 on BP was much stronger in obese individuals (BMI ≥ 30) than non-obese individuals and the effect of BMI on BP was strongest in individuals with the homozygous A allele of rs13390641.Conclusions: Our analyses that included interactions between SNPs and environmental factors identified a genetic variant associated with BP that was overlooked in standard analyses in which only genetic factors were included. This result also revealed a potential mechanism that integrates genetic factors and obesity related traits in the development of high BP.

Original languageEnglish
Article number65
JournalBMC Medical Genetics
Volume15
Issue number1
DOIs
Publication statusPublished - 2014 Jun 5

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Gene-Environment Interaction
Genome
Blood Pressure
Body Mass Index
Obesity
Single Nucleotide Polymorphism
Genetic Loci
Waist-Hip Ratio
Genome-Wide Association Study
Environmental Exposure
Meta-Analysis

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Kim, Yun K. ; Kim, Youngdoe ; Hwang, Mi Y. ; Shimokawa, Kazuro ; Won, Sungho ; Kato, Norihiro ; Tabara, Yasuharu ; Yokota, Mitsuhiro ; Han, Bok Ghee ; Lee, Jong Ho ; Kim, Bong Jo. / Identification of a genetic variant at 2q12.1 associated with blood pressure in East-Asians by genome-wide scan including gene-environment interactions. In: BMC Medical Genetics. 2014 ; Vol. 15, No. 1.
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author = "Kim, {Yun K.} and Youngdoe Kim and Hwang, {Mi Y.} and Kazuro Shimokawa and Sungho Won and Norihiro Kato and Yasuharu Tabara and Mitsuhiro Yokota and Han, {Bok Ghee} and Lee, {Jong Ho} and Kim, {Bong Jo}",
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Identification of a genetic variant at 2q12.1 associated with blood pressure in East-Asians by genome-wide scan including gene-environment interactions. / Kim, Yun K.; Kim, Youngdoe; Hwang, Mi Y.; Shimokawa, Kazuro; Won, Sungho; Kato, Norihiro; Tabara, Yasuharu; Yokota, Mitsuhiro; Han, Bok Ghee; Lee, Jong Ho; Kim, Bong Jo.

In: BMC Medical Genetics, Vol. 15, No. 1, 65, 05.06.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of a genetic variant at 2q12.1 associated with blood pressure in East-Asians by genome-wide scan including gene-environment interactions

AU - Kim, Yun K.

AU - Kim, Youngdoe

AU - Hwang, Mi Y.

AU - Shimokawa, Kazuro

AU - Won, Sungho

AU - Kato, Norihiro

AU - Tabara, Yasuharu

AU - Yokota, Mitsuhiro

AU - Han, Bok Ghee

AU - Lee, Jong Ho

AU - Kim, Bong Jo

PY - 2014/6/5

Y1 - 2014/6/5

N2 - Background: Genome-wide association studies have identified many genetic loci associated with blood pressure (BP). Genetic effects on BP can be altered by environmental exposures via multiple biological pathways. Especially, obesity is one of important environmental risk factors that can have considerable effect on BP and it may interact with genetic factors. Given that, we aimed to test whether genetic factors and obesity may jointly influence BP.Methods: We performed meta-analyses of genome-wide association data for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that included analyses of interaction between single nucleotide polymorphisms (SNPs) and the obesity-related anthropometric measures, body mass index (BMI), height, weight, and waist/hip ratio (WHR) in East-Asians (n = 12,030).Results: We identified that rs13390641 on 2q12.1 demonstrated significant association with SBP when the interaction between SNPs and BMI was considered (P < 5 × 10 -8). The gene located nearest to rs13390641, TMEM182, encodes transmembrane protein 182. In stratified analyses, the effect of rs13390641 on BP was much stronger in obese individuals (BMI ≥ 30) than non-obese individuals and the effect of BMI on BP was strongest in individuals with the homozygous A allele of rs13390641.Conclusions: Our analyses that included interactions between SNPs and environmental factors identified a genetic variant associated with BP that was overlooked in standard analyses in which only genetic factors were included. This result also revealed a potential mechanism that integrates genetic factors and obesity related traits in the development of high BP.

AB - Background: Genome-wide association studies have identified many genetic loci associated with blood pressure (BP). Genetic effects on BP can be altered by environmental exposures via multiple biological pathways. Especially, obesity is one of important environmental risk factors that can have considerable effect on BP and it may interact with genetic factors. Given that, we aimed to test whether genetic factors and obesity may jointly influence BP.Methods: We performed meta-analyses of genome-wide association data for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that included analyses of interaction between single nucleotide polymorphisms (SNPs) and the obesity-related anthropometric measures, body mass index (BMI), height, weight, and waist/hip ratio (WHR) in East-Asians (n = 12,030).Results: We identified that rs13390641 on 2q12.1 demonstrated significant association with SBP when the interaction between SNPs and BMI was considered (P < 5 × 10 -8). The gene located nearest to rs13390641, TMEM182, encodes transmembrane protein 182. In stratified analyses, the effect of rs13390641 on BP was much stronger in obese individuals (BMI ≥ 30) than non-obese individuals and the effect of BMI on BP was strongest in individuals with the homozygous A allele of rs13390641.Conclusions: Our analyses that included interactions between SNPs and environmental factors identified a genetic variant associated with BP that was overlooked in standard analyses in which only genetic factors were included. This result also revealed a potential mechanism that integrates genetic factors and obesity related traits in the development of high BP.

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