Interethnic analyses of blood pressure loci in populations of East Asian and European descent

Takeuchi, Fumihiko; Akiyama, Masato; Matoba, Nana; Katsuya, Tomohiro; Nakatochi, Masahiro; Tabara, Yasuharu; Narita, Akira; W-Y., Saw; Moon, Sanghoon; Spracklen, Cassandra N.; J-F., Chai; Kim, Yoon Jun; Liang, Zhang; Wang, C; Li, H; Wu, Jing; Dorajoo, Rajkumar; Nierenberg, Jovia L.; Wang, Y X; He, Jiang; Bennett, Derrick; Takahashi, Atushi; Momozawa, Yukihide; Hirata, Makoto; Matsuda, Koichi; Rakugi, Hiromi; Nakashima, Eitaro; Isono, Motohide; Shirota, Matsuyuki; Hozawa, Atsushi; Ichihara, Sahoko; Matsubara, Tatsuaki; Yamamoto, Ken; Kohara, Katsuhiko; Igase, Michiya; Han, Sohee; Gordon‐Larsen, Penny; Huang, Wei; Lee, N R; Adair, Linda S.; Hwang, Mi Yeong; Lee, J; Chee, Miao Ling; Sabanayagam, Charumathi; Zhao, Wanting; Liu, Jing; Reilly, Dermot F.; Sun, Liang; Huo, Shaofeng; Edwards, Todd L.; Long, Jirong; L-C., Chang; C-H., Chen; Yuan, Jian‐Min; Wp, Koh; Friedlander, Yechiel; Kelly, Tanika N.; Wei, Wen Bin; Xu, Liang; Cai, Hui; Yb, Xiang; Lin, Keng‐Hung; Clarke, Robert; Walters, Robin G.; Millwood, Iona Y.; Li, L; Chambers, John C.; Kooner, Jaspal S.; Elliott, Paul; Harst, Pim van der; Chen, Z; Sasaki, Makoto; X-O., Shu; Jonas, Jost B.; Heng, CK; Yt, Chen; Wang, Zheng; Lin, Xu; Yy, Teo; Tai, E. Shyong; Cheng, Ching‐Yu; Wong, Tien Yin; Sim, Xueling; Mohlke, Karen L.; Yamamoto, Masayuki; B-J., Kim; Miki, Tetsuro; Nabika, Toru; Yokota, Mitsuhiro; Kamatani, Yoichiro; Kubo, Michiaki; Kato, Norihiro

doi:10.1038/s41467-018-07345-0

Cited by 85 publications

(71 citation statements)

References 42 publications

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“…In the participants with sodium intake <2 g/day, we found significant association of rs67617923 in EML6 with increased risk of hypertension. While associations of several genetic variants in EML6 (e.g., rs17046380, rs72806698) with hypertension have been noted previously [40], rs67617923 is a novel genetic variant that was newly discovered in our study. Future studies to replicate this polymorphism association, and efforts to uncover the role of EML6 in blood pressure, are needed.…”

Section: Discussionsupporting

confidence: 47%

Identification of Genetic Factors Underlying the Association between Sodium Intake Habits and Hypertension Risk

et al. 2020

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The role of sodium in hypertension remains unresolved. Although genetic factors have a significant impact on high blood pressure, studies comparing genetic susceptibility between people with low and high sodium diets are lacking. We aimed to investigate the genetic variations related to hypertension according to sodium intake habits in a large Korean population-based study. Data for a total of 57,363 participants in the Korean Genome and Epidemiology Study Health Examination were analyzed. Sodium intake was measured by a semi-quantitative food frequency questionnaire. We classified participants according to sodium intake being less than or greater than 2 g/day. We used logistic regression to test single-marker variants for genetic association with a diagnosis of hypertension, adjusting for age, sex, body mass index, exercise, alcohol, smoking, potassium intake, principal components 1, and principal components 2. Significant associations were defined as p < 5 × 10−8. In participants whose sodium intake was greater than 2 g/day, chromosome 6 open reading frame 10 (C6orf10)-human leukocyte antigen (HLA)-DQB1 rs6913309, ring finger protein (RNF)213 rs112735431, glycosylphosphatidylinositol anchored molecule-like (GML)- cytochrome P450 family 11 subfamily B member 1(CYP11B1) rs3819496, myosin light chain 2 (MYL2)-cut like homeobox 2 (CUX2) rs12229654, and jagged1 (JAG1) rs1887320 were significantly associated with hypertension. In participants whose intake was less than 2 g/day, echinoderm microtubule-associated protein-like 6(EML6) rs67617923 was significantly associated with hypertension. Genetic susceptibility associated with hypertension differed according to sodium intake. Identifying gene variants that contribute to the dependence of hypertension on sodium intake status could make possible more individualized nutritional recommendations for preventing cardiovascular diseases.

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Section: Discussionsupporting

confidence: 47%

Identification of Genetic Factors Underlying the Association between Sodium Intake Habits and Hypertension Risk

et al. 2020

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“…They found variants at this locus were associated with reduced NPR3 mRNA and changes to chromatin structure, supporting a regulatory role leading to increases in vascular smooth muscle proliferation and suggesting a mechanism which can be a therapeutic target for BP. Overall with examining the top ten prioritized BP genes by Deo et al (2014) (ANTXR2, NPR3, MECOM, PLCE1, ENPEP, PDGFRA, CACNB2, ARID5B, MRVI1, and GUCY1B3) eight of the associations have been validated by GWAS and mechanisms characterized by experimental work and indicate effects on BP (Rippe et al, 2017;Takeuchi et al, 2018;Giri et al, 2019;Kichaev et al, 2019) -only ANTXR2 2 and PDGFRA 3 have not been validated in recent BP GWAS. The gene GUCY1B3, ranked tenth by Deo et al (2014), and JAG1 (ranked 11th) have consistently been studied in relation to BP and nitric oxide regulation (Rippe et al, 2019).…”

Section: Past and Present Cardiovascular Machine Learning Prioritizationmentioning

confidence: 99%

Reaching the End-Game for GWAS: Machine Learning Approaches for the Prioritization of Complex Disease Loci

et al. 2020

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“…To further describe the intrinsic and acquired gene sets, we determined whether or not genes that present with either an intrinsic or acquired sex difference in endothelial cells were targets in major genome-wide association studies (GWAS). We analysed GWAS for coronary artery disease (CAD) 11 , inflammatory bowel disease 12 , Crohn's disease 12 , ulcerative colitis 12 , Alzheimer's disease 13 , body mass index 14 , heel bone mineral density 15 , height 16 , hypertension 17 , multiple sclerosis 18 , rheumatoid arthritis 19 , and type 2 diabetes mellitus 20 . Specifics of the used GWAS studies can be found in Suppl.…”

Section: Protein Associations To Intrinsic and Acquired Regulatory Sementioning

confidence: 99%

Intrinsic transcriptomic sex differences in human endothelial cells at birth and in adults are associated with coronary artery disease targets

Hartman

Kapteijn

Haitjema

et al. 2020

Sci Rep

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Sex differences in endothelial cell (EC) biology may reflect intrinsic differences driven by chromosomes or sex steroid exposure and gender differences accumulated over life. We analysed EC gene expression data from boy-girl twins at birth and in non-twin adults to detect sex differences at different stages of life, and show that 14-25% of the EC transcriptome is sex-biased. By combining data from both stages of life, we identified sex differences that are present at birth and maintained throughout life, and those that are acquired over life. Promisingly, we found that genes that present with an acquired sex difference in ECs are more likely to be targets of sex steroids. Annotating both gene sets with data from multiple genome-wide association studies (GWAS) revealed that genes with an intrinsic sex difference in ECs are enriched for coronary artery disease GWAS hits. This study underscores the need for treating sex as a biological variable. Abbreviations CAD Coronary artery disease DEG Differentially expressed gene EC Endothelial cell HAEC Human aortic endothelial cell HUVEC Human umbilical vein endothelial cell GWAS Genome-wide association study Endothelial cells (ECs) are located at the innermost lining of all vessels and are responsible for circulatory homeostasis. ECs are implicated in a plethora of functions, such as water and nutrient transfer, inflammation, vascular tension, hemostasis, and angiogenesis 1. Differences in EC biology between the sexes have been described, indicating that sex is an important variable in EC biology 2. Studies focussing on functional differences, i.e. migration, proliferation, and shear stress response, imply sex differences in regulation of key endothelial pathways, such as the redox system 3-5. Differences between female and male cells might be present from birth onwards, or acquired later in life because of sex steroid exposure and gender differences. Pinpointing master regulators herein has been difficult, as differences between the sexes may be caused by sex hormones and/or sex chromosomes, which are difficult to study separately or to dissect. Transcriptomic studies of female and male (endothelial) cells shed light on differentially expressed genes (DEGs) between the sexes and their regulators, but few have been performed thus far on ECs 4. Tissue-specific comparisons have been made using publicly available data from the

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Interethnic analyses of blood pressure loci in populations of East Asian and European descent

Cited by 85 publications

References 42 publications

Identification of Genetic Factors Underlying the Association between Sodium Intake Habits and Hypertension Risk

Identification of Genetic Factors Underlying the Association between Sodium Intake Habits and Hypertension Risk

Reaching the End-Game for GWAS: Machine Learning Approaches for the Prioritization of Complex Disease Loci

Intrinsic transcriptomic sex differences in human endothelial cells at birth and in adults are associated with coronary artery disease targets

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