Genome-wide association study for vascular aging highlights pathways shared with cardiovascular traits in Koreans

被引：2

作者：

Ahn, JaeKyoung ^{[1
,2
]}

Jeong, Hankyeol ^{[1
,2
]}

Seo, Bo-Gyeong ^{[1
,3
]}

Park, Ki-Soo ^{[4
,5
,6
]}

Hwangbo, Cheol ^{[1
,3
]}

Kim, Han-Gyul ^{[7
]}

Koh, Jin-Sin ^{[7
]}

Kim, Jaemin ^{[1
,2
]}

机构：

[1] Gyeongsang Natl Univ, Div Appl Life Sci BK21 Four, Jinju, South Korea

[2] Gyeongsang Natl Univ, Inst Agr & Life Sci, Jinju, South Korea

[3] Gyeongsang Natl Univ, Coll Natl Sci, Div Life Sci, Jinju, South Korea

[4] Gyeongsang Natl Univ, Coll Med, Dept Prevent Med, Jinju, South Korea

[5] Gyeongsang Natl Univ, Inst Hlth Sci, Jinju, South Korea

[6] Gyeongsang Natl Univ Hosp, Ctr Farmers Safety & Hlth, Jinju, South Korea

[7] Gyeongsang Natl Univ, Gyeongsang Natl Univ Hosp, Dept Internal Med, Sch Med, Jinju, South Korea

来源：

FRONTIERS IN CARDIOVASCULAR MEDICINE | 2022年 / 9卷

关键词：

vascular aging; GWAS; endothelial dysfunction; prevention; cardiovascular disease; REACTIVE HYPEREMIA INDEX; RISK; AUTOPHAGY; SCHIZOPHRENIA; INFLAMMATION; EXPRESSION; SURVIVAL; GENES; BLOOD; SERUM;

D O I：

10.3389/fcvm.2022.1058308

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Vascular aging plays a pivotal role in the morbidity and mortality of older people. Reactive hyperemia index (RHI) detected by pulse amplitude tonometry (PAT) is a non-invasive measure of vascular endothelial function and aging-induced pathogenesis of both microvascular and macrovascular diseases. We conducted a genome-wide association study (GWAS) to comprehensively identify germline genetic variants associated with vascular aging in a Korean population, which revealed 60 suggestive genes underlying angiogenesis, inflammatory response in blood vessels, and cardiovascular diseases. Subsequently, we show that putative protective alleles were significantly enriched in an independent population with decelerated vascular aging phenotypes. Finally, we show the differential mRNA expression levels of putative causal genes in aging human primary endothelial cells via quantitative real-time polymerase chain reaction (PCR). These results highlight the potential contribution of genetic variants in the etiology of vascular aging and may suggest the link between vascular aging and cardiovascular traits.

引用

页数：12

共 77 条

[1] Measurement of endothelial function and its clinical utility for cardiovascular risk [J].

Al-Qaisi, Mo ;

Kharbanda, Rajesh K. ;

Mittal, Tarun K. ;

Donald, Ann E. .

VASCULAR HEALTH AND RISK MANAGEMENT, 2008, 4 (03) :647-652

[2] A global reference for human genetic variation [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Wang, Jun ;

Wilson, Richard K. ;

Boerwinkle, Eric ;

Doddapaneni, Harsha ;

Han, Yi ;

Korchina, Viktoriya ;

Kovar, Christie ;

Lee, Sandra ;

Muzny, Donna ;

Reid, Jeffrey G. ;

Zhu, Yiming ;

Chang, Yuqi ;

Feng, Qiang ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Lan, Tianming ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Liu, Shengmao ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Tang, Meifang ;

Wang, Bo .

NATURE, 2015, 526 (7571) :68-+

[3] Improved Detection of Common Variants Associated with Schizophrenia by Leveraging Pleiotropy with Cardiovascular-Disease Risk Factors [J].

Andreassen, Ole A. ;

Djurovic, Srdjan ;

Thompson, Wesley K. ;

Schork, Andrew J. ;

Kendler, Kenneth S. ;

O'Donovan, Michael C. ;

Rujescu, Dan ;

Werge, Thomas ;

van de Bunt, Martijn ;

Morris, Andrew P. ;

McCarthy, Mark I. ;

Roddey, J. Cooper ;

McEvoy, Linda K. ;

Desikan, Rahul S. ;

Dale, Anders M. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2013, 92 (02) :197-209

[4] Reduced Expression of the Co-regulator TLE1 in Type 2 Diabetes Is Associated with Increased Islet α-Cell Number [J].

Armour, Sarah L. ;

Anderson, Scott J. ;

Richardson, Sarah J. ;

Ding, Yuchun ;

Carey, Chris ;

Lyon, James ;

Maheshwari, Rashmi R. ;

Al-Jandami, Najwa ;

Krasnogor, Natalio ;

Morgan, Noel G. ;

MacDonald, Patrick ;

Shaw, James A. M. ;

White, Michael G. .

ENDOCRINOLOGY, 2020, 161 (04)

[5] Altered gene expression pattern indicates the differential regulation of the immune response system as an important factor in cardiac aging [J].

Bartling, Babett ;

Niemann, Katja ;

Pliquett, Rainer U. ;

Treede, Hendrik ;

Simm, Andreas .

EXPERIMENTAL GERONTOLOGY, 2019, 117 :13-20

[6]

Beckles GL, 2013, MMWR-MORBID MORTAL W, V62, P99

[7] Genome-wide association study (GWAS)-identified disease risk alleles do not compromise human longevity [J].

Beekman, Marian ;

Nederstigt, Christa ;

Suchiman, H. Eka D. ;

Kremer, Dennis ;

van der Breggen, Ruud ;

Lakenberg, Nico ;

Alemayehu, Wendimagegn Ghidey ;

de Craen, Anton J. M. ;

Westendorp, Rudi G. J. ;

Boomsma, Dorret I. ;

de Geus, Eco J. C. ;

Houwing-Duistermaat, Jeanine J. ;

Heijmans, Bastiaan T. ;

Slagboom, P. Eline .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (42) :18046-18049

[8] Ageing, tumour necrosis factor-alpha (TNF-α) and atherosclerosis [J].

Bruunsgaard, H ;

Skinhoj, P ;

Pedersen, AN ;

Schroll, M ;

Pedersen, BK .

CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2000, 121 (02) :255-260

[9] The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019 [J].

Buniello, Annalisa ;

MacArthur, Jacqueline A. L. ;

Cerezo, Maria ;

Harris, Laura W. ;

Hayhurst, James ;

Malangone, Cinzia ;

McMahon, Aoife ;

Morales, Joannella ;

Mountjoy, Edward ;

Sollis, Elliot ;

Suveges, Daniel ;

Vrousgou, Olga ;

Whetzel, Patricia L. ;

Amode, Ridwan ;

Guillen, Jose A. ;

Riat, Harpreet S. ;

Trevanion, Stephen J. ;

Hall, Peggy ;

Junkins, Heather ;

Flicek, Paul ;

Burdett, Tony ;

Hindorff, Lucia A. ;

Cunningham, Fiona ;

Parkinson, Helen .

NUCLEIC ACIDS RESEARCH, 2019, 47 (D1) :D1005-D1012

[10] Power failure: why small sample size undermines the reliability of neuroscience [J].

Button, Katherine S. ;

Ioannidis, John P. A. ;

Mokrysz, Claire ;

Nosek, Brian A. ;

Flint, Jonathan ;

Robinson, Emma S. J. ;

Munafo, Marcus R. .

NATURE REVIEWS NEUROSCIENCE, 2013, 14 (05) :365-376

← 1 2 3 4 5 6 7 8 →