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Meta-Analysis
. 2014 Jun 5;15:65.
doi: 10.1186/1471-2350-15-65.

Identification of a Genetic Variant at 2q12.1 Associated With Blood Pressure in East Asians by Genome-Wide Scan Including Gene-Environment Interactions

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Free PMC article
Meta-Analysis

Identification of a Genetic Variant at 2q12.1 Associated With Blood Pressure in East Asians by Genome-Wide Scan Including Gene-Environment Interactions

Yun Kyoung Kim et al. BMC Med Genet. .
Free PMC article

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.

Figures

Figure 1
Figure 1
Overall study scheme. We carried out a genome-wide scan for BP-associated (SBP and DBP) SNPs that included interaction terms between SNPs and the anthropometric measures BMI, height, weight, and WHR. After the three-stage analysis (discovery, replication 1, replication 2), we identified a SNP that was strongly associated with SBP by a linear regression model that incorporated interaction between SNPs and BMI.
Figure 2
Figure 2
Effect size of BMI and rs13390641 on BP. (a) Effect of BMI on SBP and DBP in the three rs13390641 genotypes. (b) Effect of rs13390641 on SBP and DBP in the four BMI groups. Group 1: BMI < 18.5, Group 2: 18.5 ≤ BMI < 25, Group 3: 25 ≤ BMI < 30, and Group 4: BMI ≥ 30. Data are the mean ± standard deviation.

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