Fetuin-A and its genetic association with cardiometabolic disease

被引：6
作者：
Al Ali, Lawien [1 ]
van de Vegte, Yordi J. [1 ]
Said, M. Abdullah [1 ]
Groot, Hilde E. [1 ]
Hendriks, Tom [1 ]
Yeung, Ming Wai [1 ]
Lipsic, Erik [1 ]
van der Harst, Pim [1 ,2 ]
机构：
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, POB 30-001,Hanzepl 1, NL-9700 RB Groningen, Netherlands
[2] Univ Utrecht, Univ Med Ctr Utrecht, Dept Heart & Lungs, Utrecht, Netherlands
来源：
SCIENTIFIC REPORTS | 2023年 / 13卷 / 01期
关键词：
ALPHA(2)-HEREMANS-SCHMID GLYCOPROTEIN/FETUIN-A; MENDELIAN RANDOMIZATION; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; RISK; INSTRUMENTS; PLEIOTROPY; INHIBITOR; VARIANTS; ADULTS;
D O I：
10.1038/s41598-023-48600-9
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Fetuin-A acts as both an inhibitor of calcification and insulin signaling. Previous studies reported conflicting results on the association between fetuin-A and cardiometabolic diseases. We aim to provide further insights into the association between genetically predicted levels of fetuin-A and cardiometabolic diseases using a Mendelian randomization strategy. Genetic variants associated with fetuin-A and their effect sizes were obtained from previous genetic studies. A series of two-sample Mendelian randomization analyses in 412,444 unrelated individuals from the UK Biobank did not show evidence for an association of genetically predicted fetuin-A with any stroke, ischemic stroke, or myocardial infarction. We do find that increased levels of genetically predicted fetuin-A are associated with increased risk of type 2 diabetes (OR = 1.21, 95%CI 1.13-1.30, P = < 0.01). Furthermore, genetically predicted fetuin-A increases the risk of coronary artery disease in individuals with type 2 diabetes, but we did not find evidence for an association between genetically predicted fetuin-A and coronary artery disease in those without type 2 diabetes (P for interaction = 0.03). One SD increase in genetically predicted fetuin-A decreases risk of myocardial infarction in women, but we do not find evidence for an association between genetically predicted fetuin-A and myocardial infarction in men (P for interaction = < 0.01). Genetically predicted fetuin-A is associated with type 2 diabetes. Furthermore, type 2 diabetes status modifies the association of genetically predicted fetuin-A with coronary artery disease, indicating that fetuin-A increases risk in individuals with type 2 diabetes. Finally, higher genetically predicted fetuin-A reduces the risk of myocardial infarction in women, but we do not find evidence for an association between genetically predicted fetuin-A and myocardial infarction in men.
引用
收藏
页数：11
相关论文
共 35 条
[1]   A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization [J].
Bowden, Jack ;
Del Greco, Fabiola M. ;
Minelli, Cosetta ;
Smith, George Davey ;
Sheehan, Nuala ;
Thompson, John .
STATISTICS IN MEDICINE, 2017, 36 (11) :1783-1802
[2]   Assessing the suitability of summary data for two-sample Mendelian randomization analyses using MR-Egger regression: the role of the I2 statistic [J].
Bowden, Jack ;
Del Greco, Fabiola M. ;
Minelli, Cosetta ;
Smith, George Davey ;
Sheehan, Nuala A. ;
Thompson, John R. .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2016, 45 (06) :1961-1974
[3]   Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression [J].
Bowden, Jack ;
Smith, George Davey ;
Burgess, Stephen .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2015, 44 (02) :512-525
[4]   A robust and efficient method for Mendelian randomization with hundreds of genetic variants [J].
Burgess, Stephen ;
Foley, Christopher N. ;
Allara, Elias ;
Staley, James R. ;
Howson, Joanna M. M. .
NATURE COMMUNICATIONS, 2020, 11 (01)
[5]   Avoiding bias from weak instruments in Mendelian randomization studies [J].
Burgess, Stephen ;
Thompson, Simon G. .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2011, 40 (03) :755-764
[6]   The UK Biobank resource with deep phenotyping and genomic data [J].
Bycroft, Clare ;
Freeman, Colin ;
Petkova, Desislava ;
Band, Gavin ;
Elliott, Lloyd T. ;
Sharp, Kevin ;
Motyer, Allan ;
Vukcevic, Damjan ;
Delaneau, Olivier ;
O'Connell, Jared ;
Cortes, Adrian ;
Welsh, Samantha ;
Young, Alan ;
Effingham, Mark ;
McVean, Gil ;
Leslie, Stephen ;
Allen, Naomi ;
Donnelly, Peter ;
Marchini, Jonathan .
NATURE, 2018, 562 (7726) :203-+
[7]   Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome [J].
Del Greco, Fabiola M. ;
Minelli, Cosetta ;
Sheehanc, Nuala A. ;
Thompsonc, John R. .
STATISTICS IN MEDICINE, 2015, 34 (21) :2926-2940
[8]   Association of AHSG Gene Polymorphisms With Fetuin-A Plasma Levels and Cardiovascular Diseases in the EPIC-Potsdam Study [J].
Fisher, Eva ;
Stefan, Norbert ;
Saar, Kathrin ;
Drogan, Dagmar ;
Schulze, Matthias B. ;
Fritsche, Andreas ;
Joost, Hans-Georg ;
Haering, Hans-Ulrich ;
Hubner, Norbert ;
Boeing, Heiner ;
Weikert, Cornelia .
CIRCULATION-CARDIOVASCULAR GENETICS, 2009, 2 (06) :607-U192
[9]   The MR-Base platform supports systematic causal inference across the human phenome [J].
Hemani, Gibran ;
Zhengn, Jie ;
Elsworth, Benjamin ;
Wade, Kaitlin H. ;
Haberland, Valeriia ;
Baird, Denis ;
Laurin, Charles ;
Burgess, Stephen ;
Bowden, Jack ;
Langdon, Ryan ;
Tan, Vanessa Y. ;
Yarmolinsky, James ;
Shihab, Hashem A. ;
Timpson, Nicholas J. ;
Evans, David M. ;
Relton, Caroline ;
Martin, Richard M. ;
Smith, George Davey ;
Gaunt, Tom R. ;
Haycock, Philip C. .
ELIFE, 2018, 7
[10]  
Hemani G, 2017, PLOS GENET, V13, DOI [10.1371/journal.pgen.1007081, 10.1371/journal.pgen.1007149]
1234