Abstract
Recently, new loci related to body mass index (BMI) or blood pressure (BP) have been identified respectively in genome-wide association studies (GWAS). However, limited studies focused on jointly associated genetic variance between systolic pressure (SBP), diastolic pressure (DBP) and BMI. Therefore, a bivariate twin study was performed to explore the genetic variants associated with BMI-SBP, BMI-DBP and SBP-DBP. A total of 380 twin pairs (137 dizygotic pairs and 243 monozygotic pairs) recruited from Qingdao Twin Registry system were used to access the genetic correlations (0.2108 for BMI-SBP, 0.2345 for BMI-DBP, and 0.6942 for SBP-DBP, respectively) by bivariate Cholesky decomposition model. Bivariate GWAS in 137 dizygotic pairs nominated 27 single identified 27 quantitative trait nucleotides (QTNs) for BMI and SBP, 27 QTNs for BMI and DBP, and 25 QTNs for SBP and DBP with the suggestive P-value threshold of 1×10−5. After imputation, we found eight SNPs, one for both BMI-SBP and SBP-DBP, and eight for SBP-DBP, exceed significant statistic level. Expression quantitative trait loci analysis identified rs4794029 as new significant eQTL in tissues related to BMI and SBP. Also, we found 6 new significant eQTLs (rs4400367, rs10113750, rs11776003, rs3739327, rs55978930, and rs4794029) in tissues were related to SBP and DBP. Gene-based analysis identified nominally associated genes (P < 0.05) with BMI-SBP, BMI-DBP, and SBP-DBP, respectively, such as PHOSPHO1, GNGT2, KEAP1, and S1PR5. In the pathway analysis, we found some pathways associated with BMI-SBP, BMI-DBP and SBP-DBP, such as prion diseases, IL5 pathway, cyclin E associated events during G1/S transition, TGF beta signaling pathway, G βγ signaling through PI3Kγ, prolactin receptor signaling etc. These findings may enrich the results of genetic variants related to BMI and BP traits, and provide some evidences to future study the pathogenesis of hypertension and obesity in the northern Chinese population.
Highlights
Hypertension and obesity are public health challenges worldwide [1, 2]
It was demonstrated that the genetic correlation between body mass index (BMI) and blood pressure (BP) ranged from 0.15 to 0.49, and additive genetic factors accounted for 65%-86% of the phenotypic correlations between BMI and BP components [19,20,21,22,23]
Genetic variance and genes potentially related to hypertension and obesity still remain unknown, and need further exploration. We designed this bivariate twin study to: (1) identify genetic variants associated with BMI-SBP, BMI-DBP and SBP-DBP, respectively; and (2) identify potential causal genetic variation; (3) determine the common pathways associated with hypertension and obesity
Summary
Hypertension and obesity are public health challenges worldwide [1, 2]. Hypertension increases the risk of several diseases, such as chronic renal disease, stroke, dementia and coronary artery disease, etc. [3,4,5,6,7]. Obesity is related to cardiovascular disease, diabetes, cancer and increase global burden worldwide [8,9,10] Both of hypertension and obesity are complex chronic diseases effected by genetic and environmental factors [11, 12]. Genetic variance and genes potentially related to hypertension and obesity still remain unknown, and need further exploration. We designed this bivariate twin study to: (1) identify genetic variants associated with BMI-SBP, BMI-DBP and SBP-DBP, respectively; and (2) identify potential causal genetic variation; (3) determine the common pathways associated with hypertension and obesity
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