Identification of Putative Causal Relationships Between Type 2 Diabetes and Blood-Based Biomarkers in East Asians by Mendelian Randomization
Zhang, Haoyang LU
; Xiu, Xuehao
; Yang, Yuedong
; Yang, Yuanhao
and Zhao, Huiying
(2022)
In American Journal of Epidemiology
191(11).
p.1867-1876
- Abstract
Observational studies have revealed phenotypic associations between type 2 diabetes (T2D) and many biomarkers. However, causality between these conditions in East Asians is unclear. We leveraged genome-wide association study (GWAS) summary statistics on T2D (n = 77,418 cases; n = 356,122 controls) from the Asian Genetic Epidemiology Network (sample recruited during 2001-2011) and GWAS summary statistics on 42 biomarkers (n = 12,303-143,658) from BioBank Japan (sample recruited during 2003-2008) to investigate causal relationships between T2D and biomarkers. Applications of Mendelian randomization approaches consistently revealed genetically instrumented associations of T2D with increased serum potassium levels (liability-scale β =... (More)
Observational studies have revealed phenotypic associations between type 2 diabetes (T2D) and many biomarkers. However, causality between these conditions in East Asians is unclear. We leveraged genome-wide association study (GWAS) summary statistics on T2D (n = 77,418 cases; n = 356,122 controls) from the Asian Genetic Epidemiology Network (sample recruited during 2001-2011) and GWAS summary statistics on 42 biomarkers (n = 12,303-143,658) from BioBank Japan (sample recruited during 2003-2008) to investigate causal relationships between T2D and biomarkers. Applications of Mendelian randomization approaches consistently revealed genetically instrumented associations of T2D with increased serum potassium levels (liability-scale β = 0.04-0.10; P = 6.41 × 10-17-9.85 × 10-5) and decreased serum chloride levels (liability-scale β = -0.16 to -0.06; P = 5.22 × 10-27-3.14 × 10-5), whereas these 2 biomarkers showed no causal effects on T2D. Heritability Estimation Using Summary Statistics (ρ-HESS) and summary-data-based Mendelian randomization highlighted 27 genomic regions and 3 genes (α-1,3-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase (MGAT1), transducing-like enhancer (TLE) family member 1, transcriptional corepressor (TLE1), and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)) that interactively associated with the shared genetics underlying T2D and the 2 biomarkers. Thus, T2D may causally affect serum potassium and chloride levels among East Asians. In contrast, the relationships of potassium and chloride with T2D are not causal, suggesting the importance of monitoring electrolyte disorders for T2D patients.
(Less)
- author
- Zhang, Haoyang
LU
; Xiu, Xuehao
; Yang, Yuedong
; Yang, Yuanhao
and Zhao, Huiying
- publishing date
- 2022-10-20
- type
- Contribution to journal
- publication status
- published
- keywords
- Humans, Diabetes Mellitus, Type 2/genetics, Mendelian Randomization Analysis, Genome-Wide Association Study, Chlorides, Biomarkers, Potassium, Polymorphism, Single Nucleotide
- in
- American Journal of Epidemiology
- volume
- 191
- issue
- 11
- pages
- 1867 - 1876
- publisher
- Oxford University Press
- external identifiers
-
- scopus:85141888982
- pmid:35801869
- ISSN
- 0002-9262
- DOI
- 10.1093/aje/kwac118
- language
- English
- LU publication?
- no
- additional info
- © The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
- id
- d0cc5feb-1048-451a-9b70-3d069d3769b8
- date added to LUP
- 2024-02-05 14:56:41
- date last changed
- 2024-04-22 10:54:57
@article{d0cc5feb-1048-451a-9b70-3d069d3769b8,
abstract = {{<p>Observational studies have revealed phenotypic associations between type 2 diabetes (T2D) and many biomarkers. However, causality between these conditions in East Asians is unclear. We leveraged genome-wide association study (GWAS) summary statistics on T2D (n = 77,418 cases; n = 356,122 controls) from the Asian Genetic Epidemiology Network (sample recruited during 2001-2011) and GWAS summary statistics on 42 biomarkers (n = 12,303-143,658) from BioBank Japan (sample recruited during 2003-2008) to investigate causal relationships between T2D and biomarkers. Applications of Mendelian randomization approaches consistently revealed genetically instrumented associations of T2D with increased serum potassium levels (liability-scale β = 0.04-0.10; P = 6.41 × 10-17-9.85 × 10-5) and decreased serum chloride levels (liability-scale β = -0.16 to -0.06; P = 5.22 × 10-27-3.14 × 10-5), whereas these 2 biomarkers showed no causal effects on T2D. Heritability Estimation Using Summary Statistics (ρ-HESS) and summary-data-based Mendelian randomization highlighted 27 genomic regions and 3 genes (α-1,3-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase (MGAT1), transducing-like enhancer (TLE) family member 1, transcriptional corepressor (TLE1), and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)) that interactively associated with the shared genetics underlying T2D and the 2 biomarkers. Thus, T2D may causally affect serum potassium and chloride levels among East Asians. In contrast, the relationships of potassium and chloride with T2D are not causal, suggesting the importance of monitoring electrolyte disorders for T2D patients.</p>}},
author = {{Zhang, Haoyang and Xiu, Xuehao and Yang, Yuedong and Yang, Yuanhao and Zhao, Huiying}},
issn = {{0002-9262}},
keywords = {{Humans; Diabetes Mellitus, Type 2/genetics; Mendelian Randomization Analysis; Genome-Wide Association Study; Chlorides; Biomarkers; Potassium; Polymorphism, Single Nucleotide}},
language = {{eng}},
month = {{10}},
number = {{11}},
pages = {{1867--1876}},
publisher = {{Oxford University Press}},
series = {{American Journal of Epidemiology}},
title = {{Identification of Putative Causal Relationships Between Type 2 Diabetes and Blood-Based Biomarkers in East Asians by Mendelian Randomization}},
url = {{http://dx.doi.org/10.1093/aje/kwac118}},
doi = {{10.1093/aje/kwac118}},
volume = {{191}},
year = {{2022}},
}