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Liangwan Chen
Fujian Medical University Union Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4211-3842
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Background: Circulating low-density lipoprotein cholesterol (LDL-C) plays a causal role in coronary artery disease (CAD). However, genetic risk factors of CAD were not yet fully understood. The aim of the study was to identify additional factors that contributed to CAD.
Methods: We conducted integrative analysis on publicly available data from genome-wide association studies and quantitative trait locus studies by employing two-sample Mendelian randomization methods to examine the associations of gene expression and circulating protein levels with LDL-C and CAD.
Results: We found that mRNA expression levels of SORT1, PSRC1 and CELSR2 in liver cells were significantly associated with both LDL-C and CAD (P < 5.0 × 10-8). Higher expression levels of SORT1, PSRC1 and CELSR2 in the liver were significantly associated with lower circulating LDL-C level (beta= -0.142, -0.138 and -0.171, respectively) and CAD risk (beta= -0.10, -0.097 and -0.121, respectively). Expression levels of 31 genes in blood cells associated with LDL-C level were found. Expressions of PSRC1, IL6R, GGCX, VAMP8, LIPA, NT5C2, SWAP70, EIF2B2, FURIN, FES and ATP5G1 in blood cells were significantly associated with CAD. Higher circulating granulins and apolipoprotein B levels, which were strongly affected by PSRC1 and APOB variants, were significantly associated with higher LDL-C level (beta = 0.22 and 1.35) and CAD risk, with odds ratios of 1.15 (1.10-1.19) and 1.45 (1.21-1.74), respectively.
Conclusions: This study identified gene expressions in liver and blood cells and circulating granulins and apolipoprotein B that were genetically associated with LDL-C and CAD and provided evidence for exploring the potential causal relationship.
Keywords
Low-density lipoprotein cholesterol, Coronary artery disease, Genome-wide association study, Mendelian randomization
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Liangwan Chen
Fujian Medical University Union Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4211-3842
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 31 Mar, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Medical Genetics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Circulating low-density lipoprotein cholesterol (LDL-C) plays a causal role in coronary artery disease (CAD). However, genetic risk factors of CAD were not yet fully understood. The aim of the study was to identify additional factors that contributed to CAD.
Methods: We conducted integrative analysis on publicly available data from genome-wide association studies and quantitative trait locus studies by employing two-sample Mendelian randomization methods to examine the associations of gene expression and circulating protein levels with LDL-C and CAD.
Results: We found that mRNA expression levels of SORT1, PSRC1 and CELSR2 in liver cells were significantly associated with both LDL-C and CAD (P < 5.0 × 10-8). Higher expression levels of SORT1, PSRC1 and CELSR2 in the liver were significantly associated with lower circulating LDL-C level (beta= -0.142, -0.138 and -0.171, respectively) and CAD risk (beta= -0.10, -0.097 and -0.121, respectively). Expression levels of 31 genes in blood cells associated with LDL-C level were found. Expressions of PSRC1, IL6R, GGCX, VAMP8, LIPA, NT5C2, SWAP70, EIF2B2, FURIN, FES and ATP5G1 in blood cells were significantly associated with CAD. Higher circulating granulins and apolipoprotein B levels, which were strongly affected by PSRC1 and APOB variants, were significantly associated with higher LDL-C level (beta = 0.22 and 1.35) and CAD risk, with odds ratios of 1.15 (1.10-1.19) and 1.45 (1.21-1.74), respectively.
Conclusions: This study identified gene expressions in liver and blood cells and circulating granulins and apolipoprotein B that were genetically associated with LDL-C and CAD and provided evidence for exploring the potential causal relationship.
Figure 1
Figure 2
This is a list of supplementary files associated with this preprint. Click to download.
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