A Genome-Wide Association Study of a Korean Population Identifies Genetic Susceptibility to Hypertension Based on Sex-Specific Differences

Cho, Seong-Beom; Jang, Jinhwa

doi:10.3390/genes12111804

Cited by 8 publications

(3 citation statements)

References 64 publications

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“…Mutations in the ATXN2 gene were reported to be associated with susceptibility to type I diabetes, obesity, and hypertension ( Davalos-Rodriguez et al 2022 ). HECTD4 is involved in the metabolic process of glucose and is also associated with susceptibility to hypertension, with rs2074356 showing significant genetic heterogeneity in the systolic blood pressure ( Cho and Jang 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Ancestral Origins and Admixture History of Kazakhs

Lei,

Liu,

Zhang

et al. 2024

Molecular Biology and Evolution

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Kazakh people, like many other populations that settled in Central Asia, demonstrate an array of mixed anthropological features of East Eurasian (EEA) and West Eurasian (WEA) populations, indicating a possible scenario of biological admixture between already differentiated EEA and WEA populations. However, their complex biological origin and genomic makeup, as well as their genetic interaction with surrounding populations, are not well understood. In an attempt to decipher their genetic structure and population history, we conducted, to our knowledge, the first whole-genome sequencing study of Kazakhs residing in Xinjiang (KZK). We demonstrated that KZK derived their ancestries from four ancestral source populations: East Asian (∼39.7%), West Asian (∼28.6%), Siberian (∼23.6%), and South Asian (∼8.1%). The recognizable interactions of EEA and WEA ancestries in Kazakhs were dated back to the 15th century BCE. Kazakhs were genetically distinctive from Uyghurs in terms of their overall genomic makeup, although the two populations were closely related in genetics, and both showed a substantial admixture of EEA and WEA ancestries. Notably, we identified a considerable sex-biased admixture, with an excess of western males and eastern females contributing to the KZK gene pool. We further identified a set of genes that showed remarkable differentiation in KZK from the surrounding populations, including those associated with skin color (SLC24A5, OCA2), essential hypertension (HLA-DQB1), hypertension (MTHFR, SLC35F3), and neuron development (CNTNAP2). These results advance our understanding of the complex history of contacts between Western and Eastern Eurasians, especially those situated along the old Silk Road.

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Section: Resultsmentioning

confidence: 99%

Ancestral Origins and Admixture History of Kazakhs

Lei,

Liu,

Zhang

et al. 2024

Molecular Biology and Evolution

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“…The newly found rs6990123 showed an outstanding association strength compared to others, and it participated in two-order interactions, as shown in Table 5 , to make top associated pairs with SNPs absent from the list of the top main effects. rs2074356 was reported to have a strong association with γ-GTP levels [ 35 ], and rs11066280 was reported to have a strong association with type 2 diabetes, which is closely related to γ-GTP [ 36 ]. rs12229654, which has been reported to be associated with both γ-GTP and high-density lipoprotein cholesterol [ 37 ], was also found.…”

Section: Resultsmentioning

confidence: 99%

Identification of the associations between genes and quantitative traits using entropy-based kernel density estimation

Yee

Park

2022

Genomics Inform

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Genetic associations have been quantified using a number of statistical measures. Entropy-based mutual information may be one of the more direct ways of estimating the association, in the sense that it does not depend on the parametrization. For this purpose, both the entropy and conditional entropy of the phenotype distribution should be obtained. Quantitative traits, however, do not usually allow an exact evaluation of entropy. The estimation of entropy needs a probability density function, which can be approximated by kernel density estimation. We have investigated the proper sequence of procedures for combining the kernel density estimation and entropy estimation with a probability density function in order to calculate mutual information. Genotypes and their interactions were constructed to set the conditions for conditional entropy. Extensive simulation data created using three types of generating functions were analyzed using two different kernels as well as two types of multifactor dimensionality reduction and another probability density approximation method called m-spacing. The statistical power in terms of correct detection rates was compared. Using kernels was found to be most useful when the trait distributions were more complex than simple normal or gamma distributions. A full-scale genomic dataset was explored to identify associations using the 2-h oral glucose tolerance test results and γ-glutamyl transpeptidase levels as phenotypes. Clearly distinguishable single-nucleotide polymorphisms (SNPs) and interacting SNP pairs associated with these phenotypes were found and listed with empirical p-values.

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“…[8] Similarly, a recent study showed evidence of heterogeneity of the genetic effects of hypertension-associated variants between males and females and, that the variants leading sex-speci c genetic susceptibility may relate to genes involved in steroid hormone receptor biosynthesis pathway. [9] Alongside studies in human populations, rodent models have been a valuable resource for the better understanding of hypertension and its relation to adiposity. In a recently published study, a hypotensive SPAK T243A/T243A mice also exhibited an obesity-resistant phenotype.…”

Section: Introductionmentioning

confidence: 99%

Body mass index is a mediumiator of the genetic association between STK39 and blood pressure in Mexican women

Huerta-Chagoya

Moreno-Macías

Ordóñez-Sánchez

et al. 2022

Preprint

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Background Although obesity causally relates to hypertension, the underlying genetic mechanisms are not completely understood. STK39 gene, encoding the SPAK kinase, associates with both hypertension and body mass index (BMI). In a murine model, we previously showed that the inactivation of SPAK resulted in a hypotensive and obesity-resistant phenotype. Methods We analyzed the mediator effect of BMI on the association between STK39 and systolic blood pressure (SBP) in a sample of 2,853 Mexican adults. We also assessed the STK39 expression patterns in human adipose tissue, a relevant tissue determining BMI. Results We found that a STK39 locus, tagged by rs6749447 genetic variant, has a positive and significant direct effect on blood pressure in women (B(SE) = 0.073(0.028), P = 0.010), as well as an indirect effect through the BMI (B(SE) = 0.010(0.004), P = 0.024), therefore showing that BMI is a mediator of STK39 and SBP. None of the effects were significant in men (direct effect: B(SE) = 0.030(0.031), P = 0.329; indirect effect: B(SE) = 0.124(0.255), P = 0.626). Additionally, we found that STK39 is expressed in subcutaneous adipose tissue with similar steady-state levels to PPARG and LIPE genes, and its expression is higher in women than in men (P = 0.0008). Conclusions Our results shed light on the genetic basis of obesity-induced hypertension and outline a specific locus within STK39 as an important modulator of this process.

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A Genome-Wide Association Study of a Korean Population Identifies Genetic Susceptibility to Hypertension Based on Sex-Specific Differences

Cited by 8 publications

References 64 publications

Ancestral Origins and Admixture History of Kazakhs

Ancestral Origins and Admixture History of Kazakhs

Identification of the associations between genes and quantitative traits using entropy-based kernel density estimation

Body mass index is a mediumiator of the genetic association between STK39 and blood pressure in Mexican women

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