Genome-wide association and Mendelian randomization analysis provide insights into the shared genetic architecture between high-dimensional electrocardiographic features and ischemic heart disease
Wang, Xinfeng ; Qi, Mengling ; Zhang, Haoyang LU
; Yang, Yuedong
and Zhao, Huiying
(2024)
In Human Genetics
143.
p.49-58
- Abstract
- Observational studies have revealed that ischemic heart disease (IHD) has a unique manifestation on electrocardiographic (ECG). However, the genetic relationships between IHD and ECG remain unclear. We took 12-lead ECG as phenotypes to conduct genome-wide association studies (GWAS) for 41,960 samples from UK-Biobank (UKB). By leveraging large-scale GWAS summary of ECG and IHD (downloaded from FinnGen database), we performed LD score regression (LDSC), Mendelian randomization (MR), and polygenic risk score (PRS) regression to explore genetic relationships between IHD and ECG. Finally, we constructed an XGBoost model to predict IHD by integrating PRS and ECG. The GWAS identified 114 independent SNPs significantly (P value < 5 × 10–8/800,... (More)
- Observational studies have revealed that ischemic heart disease (IHD) has a unique manifestation on electrocardiographic (ECG). However, the genetic relationships between IHD and ECG remain unclear. We took 12-lead ECG as phenotypes to conduct genome-wide association studies (GWAS) for 41,960 samples from UK-Biobank (UKB). By leveraging large-scale GWAS summary of ECG and IHD (downloaded from FinnGen database), we performed LD score regression (LDSC), Mendelian randomization (MR), and polygenic risk score (PRS) regression to explore genetic relationships between IHD and ECG. Finally, we constructed an XGBoost model to predict IHD by integrating PRS and ECG. The GWAS identified 114 independent SNPs significantly (P value < 5 × 10–8/800, where 800 denotes the number of ECG features) associated with ECG. LDSC analysis indicated significant (P value < 0.05) genetic correlations between 39 ECG features and IHD. MR analysis performed by five approaches showed a putative causal effect of IHD on four S wave related ECG features at lead III. Integrating PRS for these ECG features with age and gender, the XGBoost model achieved Area Under Curve (AUC) 0.72 in predicting IHD. Here, we provide genetic evidence supporting S wave related ECG features at lead III to monitor the IHD risk, and open up a unique approach to integrate ECG with genetic factors for pre-warning IHD (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/9e8bbc9a-cdec-4401-9f7f-d0e08a1f4201
- author
- Wang, Xinfeng
; Qi, Mengling
; Zhang, Haoyang
LU
; Yang, Yuedong
and Zhao, Huiying
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- published
- in
- Human Genetics
- volume
- 143
- pages
- 49 - 58
- publisher
- Springer
- external identifiers
-
- pmid:38180560
- scopus:85181458161
- ISSN
- 1432-1203
- DOI
- 10.1007/s00439-023-02614-5
- language
- English
- LU publication?
- no
- id
- 9e8bbc9a-cdec-4401-9f7f-d0e08a1f4201
- date added to LUP
- 2024-02-03 15:55:26
- date last changed
- 2024-02-05 07:51:37
@article{9e8bbc9a-cdec-4401-9f7f-d0e08a1f4201,
abstract = {{Observational studies have revealed that ischemic heart disease (IHD) has a unique manifestation on electrocardiographic (ECG). However, the genetic relationships between IHD and ECG remain unclear. We took 12-lead ECG as phenotypes to conduct genome-wide association studies (GWAS) for 41,960 samples from UK-Biobank (UKB). By leveraging large-scale GWAS summary of ECG and IHD (downloaded from FinnGen database), we performed LD score regression (LDSC), Mendelian randomization (MR), and polygenic risk score (PRS) regression to explore genetic relationships between IHD and ECG. Finally, we constructed an XGBoost model to predict IHD by integrating PRS and ECG. The GWAS identified 114 independent SNPs significantly (P value < 5 × 10–8/800, where 800 denotes the number of ECG features) associated with ECG. LDSC analysis indicated significant (P value < 0.05) genetic correlations between 39 ECG features and IHD. MR analysis performed by five approaches showed a putative causal effect of IHD on four S wave related ECG features at lead III. Integrating PRS for these ECG features with age and gender, the XGBoost model achieved Area Under Curve (AUC) 0.72 in predicting IHD. Here, we provide genetic evidence supporting S wave related ECG features at lead III to monitor the IHD risk, and open up a unique approach to integrate ECG with genetic factors for pre-warning IHD}},
author = {{Wang, Xinfeng and Qi, Mengling and Zhang, Haoyang and Yang, Yuedong and Zhao, Huiying}},
issn = {{1432-1203}},
language = {{eng}},
pages = {{49--58}},
publisher = {{Springer}},
series = {{Human Genetics}},
title = {{Genome-wide association and Mendelian randomization analysis provide insights into the shared genetic architecture between high-dimensional electrocardiographic features and ischemic heart disease}},
url = {{http://dx.doi.org/10.1007/s00439-023-02614-5}},
doi = {{10.1007/s00439-023-02614-5}},
volume = {{143}},
year = {{2024}},
}