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Nonlinear causal effects of estimated glomerular filtration rate on myocardial infarction risks: Mendelian randomization study

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Author(s)
Sehoon ParkSoojin LeeYaerim KimSemin ChoHyeok HuhKwangsoo KimYong Chul KimSeung Seok HanHajeong LeeJung Pyo LeeKwon Wook JooChun Soo LimYon Su KimDong Ki Kim
Keimyung Author(s)
Kim, Yae Rim
Department
Dept. of Internal Medicine (내과학)
Journal Title
BMC Med
Issued Date
2022
Volume
20
Keyword
Myocardial infarctionKidneyMendelian randomization
Abstract
Background:
Previous observational studies suggested that a reduction in estimated glomerular filtration rate (eGFR) or a supranormal eGFR value was associated with adverse cardiovascular risks. However, a previous Mendelian randomization (MR) study under the linearity assumption reported null causal effects from eGFR on myocardial infarction (MI) risks. Further investigation of the nonlinear causal effect of kidney function assessed by eGFR on the risk of MI by nonlinear MR analysis is warranted.

Methods:
In this MR study, genetic instruments for log-eGFR based on serum creatinine were developed from European samples included in the CKDGen genome-wide association study (GWAS) meta-analysis (N=567,460). Alternate instruments for log-eGFR based on cystatin C were developed from a GWAS of European individuals that included the CKDGen and UK Biobank data (N=460,826). Nonlinear MR analysis for the risk of MI was performed using the fractional polynomial method and the piecewise linear method on data from individuals of white British ancestry in the UK Biobank (N=321,024, with 12,205 MI cases).

Results:
Nonlinear MR analysis demonstrated a U-shaped (quadratic P value < 0.001) association between MI risk and genetically predicted eGFR (creatinine) values, as MI risk increased as eGFR declined in the low eGFR range and the risk increased as eGFR increased in the high eGFR range. The results were similar even after adjustment for clinical covariates, such as blood pressure, diabetes mellitus, dyslipidemia, or urine microalbumin levels, or when genetically predicted eGFR (cystatin C) was included as the exposure.

Conclusion:
Genetically predicted eGFR is significantly associated with the risk of MI with a parabolic shape, suggesting that kidney function impairment, either by reduced or supranormal eGFR, may be causally linked to a higher MI risk.
Keimyung Author(s)(Kor)
김예림
Publisher
School of Medicine (의과대학)
Citation
Sehoon Park et al. (2022). Nonlinear causal effects of estimated glomerular filtration rate on myocardial infarction risks: Mendelian randomization study. BMC Med, 20, 44. doi: 10.1186/s12916-022-02251-1
Type
Article
ISSN
1741-7015
Source
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02251-1
DOI
10.1186/s12916-022-02251-1
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44173
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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