Novel Metabolites Genetically Linked to Salt Sensitivity of Blood Pressure: Evidence from mGWAS in Chinese Population
Abstract
1. Introduction
2. Results
2.1. Basic Characteristics of the Participants
2.2. Metabolite Genome-Wide Association Analysis
2.3. Identification of Independent mQTLs
2.4. Effector Genes of Genetically Influenced Metabolites
2.5. Potential Proteins Related to Genetically Influenced Metabolites
2.6. Associations Between GIMs and SSBP
2.7. Mendelian Randomization Analyses
2.8. Construction of SNP–Gene–Metabolite Association Network Related to SSBP
2.9. Replication Analyses
3. Discussion
4. Materials and Methods
4.1. Study Population and Samples
4.2. Determination of SS and SR
4.3. Untargeted Metabolomics Profiling and Data Processing
4.4. DNA Extraction, Genotyping, and Quality Control
4.5. mGWAS Analysis
4.6. Statistical Analysis
4.7. Replication Set
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
GIM | Genetically influenced metabolite |
mGWAS | Metabolome genome-wide association study |
MR | Mendelian randomization |
LD | Linear dichroism |
SSBP | Salt sensitivity of blood pressure |
SS | Salt-sensitive |
SR | Salt-resistant |
GWAS | Genome-wide association study |
mQTLs | Metabolic quantitative trait loci |
SBP | Systolic blood pressure |
DBP | Diastolic blood pressure |
MAP | Mean arterial pressure |
uGRSs | Unweighted genetic risk scores |
wGRSs | Weighted genetic risk scores |
2SLSs | Two-stage least squares |
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Variables | Total (n = 54) | SS (n = 30) | SR (n = 24) | p |
---|---|---|---|---|
Age (year) | 57.57 ± 5.43 | 57.73 ± 5.77 | 57.38 ± 5.11 | 0.812 a |
Gender (Male, n, %) | 17 (31.5) | 8 (33.3) | 9 (30.0) | 1.000 c |
BMI (kg/m2) | 26.62 ± 3.52 | 26.39 ± 3.26 | 26.92 ± 3.86 | 0.586 a |
FBG (mmol/L) | 5.45 ± 0.63 | 5.44 ± 0.61 | 5.47 ± 0.66 | 0.924 b |
TC (mmol/L) | 5.48 ± 0.94 | 5.37 ± 1.03 | 5.61 ± 0.80 | 0.360 a |
TGs (mmol/L) | 1.83 ± 1.03 | 1.86 ± 1.09 | 1.79 ± 0.96 | 0.721 b |
LDL-C (mmol/L) | 2.32 ± 0.91 | 2.24 ± 0.88 | 2.42 ± 0.95 | 0.461 a |
HDL-C (mmol/L) | 1.95 ± 1.17 | 1.93 ± 1.21 | 1.97 ± 1.14 | 0.614 b |
SBP (mmHg) | 122.01 ± 20.45 | 114.19 ± 21.10 | 131.78 ± 14.94 | 0.001 a |
DBP (mmHg) | 78.11 ± 12.02 | 71.72 ± 10.72 | 86.10 ± 8.25 | <0.001 a |
MAP (mmHg) | 92.74 ± 13.39 | 85.87 ± 12.52 | 101.33 ± 8.78 | <0.001 a |
ΔMAP1 (mmHg) | −2.62 ± 15.14 | 10.16 ± 3.31 | −18.59 ± 5.92 | <0.001 b |
ΔMAP2 (mmHg) | −2.07 ± 10.78 | −10.48 ± 5.44 | 8.44 ± 4.81 | <0.001 a |
Smoking (n, %) | 7 (13.0) | 5 (16.7) | 2 (8.3) | 0.443 d |
Drinking (n, %) | 26 (48.1) | 16 (53.3) | 10 (41.7) | 0.563 c |
Hypertension (n, %) | 28 (51.9) | 15 (50.0) | 13 (54.2) | 0.976 c |
Family history of hypertension (n, %) | 29 (53.7) | 18 (60.0) | 11 (45.8) | 0.446 c |
GIMs | Numbers of mQTLs | SNP * | CHR | Position | Minor Allele | Other Allele | MAF | p |
---|---|---|---|---|---|---|---|---|
Arabinonic acid | 67 | rs3792688 | 14 | 36788896 | G | C | 0.010 | 7.13 × 10−21 |
Feruloylquinic acid | 46 | rs11076702 | 16 | 88774569 | A | C | 0.019 | 4.20 × 10−15 |
Phe-lle | 43 | rs11758014 | 6 | 148830586 | C | G | 0.010 | 2.73 × 10−16 |
Phe-Phe | 42 | rs111865319 | 14 | 23507554 | T | G | 0.010 | 4.08 × 10−16 |
LysoPC (0:0/22:5n-3) | 34 | rs17773637 | 2 | 103168041 | A | T | 0.010 | 1.40 × 10−13 |
Androsterone sulfate | 29 | rs193142735 | 7 | 28077870 | T | A | 0.010 | 1.34 × 10−13 |
Fumaric acid | 29 | rs117266991 | 6 | 93172013 | G | A | 0.028 | 3.96 × 10−14 |
TGs (12:0/12:0/12:0) | 24 | rs11076702 | 16 | 88774569 | A | C | 0.019 | 4.20 × 10−15 |
Glycoursodeoxycholate 3-glucuronide | 23 | rs111941908 | 2 | 29660776 | G | A | 0.019 | 9.95 × 10−14 |
Oleic acid | 19 | rs148784825 | 1 | 196024278 | C | T | 0.019 | 4.41 × 10−15 |
LysoPC (0:0/14:0) | 2 | rs7523503 | 1 | 200899804 | A | G | 0.151 | 4.60 × 10−11 |
16α-hydroxy DHEA 3-sulfate isomer | 2 | rs3782520 | 12 | 109027340 | T | C | 0.074 | 1.25 × 10−11 |
L-Cystine | 2 | rs17812386 | 9 | 113942888 | A | G | 0.029 | 1.65 × 10−13 |
X-MZ140RT42 | 2 | rs117266991 | 6 | 93172013 | G | A | 0.028 | 3.16 × 10−12 |
Glycoursocholic acid | 1 | rs117458538 | 16 | 86932146 | G | A | 0.056 | 6.90 × 10−12 |
DG (18:0/18:0) | 1 | rs146258959 | 18 | 34962385 | C | T | 0.028 | 2.40 × 10−11 |
Palmitic amide | 1 | rs118008665 | 17 | 59640888 | T | C | 0.028 | 5.92 × 10−12 |
N-Acetyl-l-aspartic acid | 1 | rs145741649 | 5 | 105503858 | A | G | 0.020 | 2.89 × 10−11 |
GIMs | Model 1 a | Model 2 b | ||||
---|---|---|---|---|---|---|
β | ORs (95%CI) | p | β | ORs (95%CI) | p | |
Arabinonic acid | −0.087 | 0.916 (0.866, 0.970) | 0.004 | −0.085 | 0.919 (0.871, 0.970) | 0.003 |
Feruloylquinic acid | −0.052 | 0.949 (0.915, 0.984) | 0.007 | −0.054 | 0.947 (0.915, 0.981) | 0.003 |
Phe-lle | −0.097 | 0.908 (0.881, 0.936) | <0.001 | −0.093 | 0.911 (0.887, 0.935) | <0.001 |
Phe-Phe | −0.088 | 0.915 (0.892, 0.939) | <0.001 | −0.087 | 0.916 (0.894, 0.939) | <0.001 |
LysoPC (0:0/22:5n-3) | 0.092 | 1.097 (1.046, 1.150) | <0.001 | 0.093 | 1.098 (1.047, 1.151) | <0.001 |
Androsterone sulfate | −0.065 | 0.937 (0.909, 0.967) | <0.001 | −0.066 | 0.937 (0.908, 0.966) | <0.001 |
Fumaric acid | −0.563 | 0.570 (0.389, 0.834) | 0.006 | −0.564 | 0.569 (0.388, 0.834) | 0.006 |
TGs (12:0/12:0/12:0) | −0.182 | 0.833 (0.794, 0.875) | <0.001 | −0.180 | 0.835 (0.796, 0.877) | <0.001 |
Glycoursodeoxycholate 3-glucuronide | −0.053 | 0.948 (0.928, 0.969) | <0.001 | −0.056 | 0.946 (0.926, 0.966) | <0.001 |
Oleic acid | −0.044 | 0.957 (0.934, 0.981) | 0.001 | −0.045 | 0.956 (0.934, 0.979) | <0.001 |
LysoPC (0:0/14:0) | −0.353 | 0.702 (0.553, 0.891) | 0.005 | −0.353 | 0.702 (0.553, 0.891) | 0.005 |
16α-hydroxy DHEA 3-sulfate isomer | −0.037 | 0.964 (0.881, 1.055) | 0.428 | −0.027 | 0.973 (0.887, 1.068) | 0.567 |
L-Cystine | −0.207 | 0.813 (0.711, 0.930) | 0.004 | −0.198 | 0.820 (0.726, 0.927) | 0.002 |
X-MZ140RT42 | −0.528 | 0.590 (0.428, 0.814) | 0.002 | −0.533 | 0.587 (0.423, 0.815) | 0.002 |
Glycoursocholic acid | −0.050 | 0.951 (0.895, 1.011) | 0.117 | −0.050 | 0.951 (0.895, 1.011) | 0.117 |
DG (18:0/18:0) | 0.068 | 1.071 (0.798, 1.437) | 0.652 | 0.068 | 1.071 (0.798, 1.437) | 0.652 |
Palmitic amide | 0.140 | 1.150 (0.673, 1.965) | 0.611 | 0.140 | 1.150 (0.673, 1.965) | 0.611 |
N-Acetyl-l-aspartic acid | −0.486 | 0.615 (0.466, 0.811) | 0.001 | −0.486 | 0.615 (0.466, 0.811) | 0.001 |
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Yang, X.; Zhang, B.; Wen, F.; Qi, H.; Zhang, F.; Xie, Y.; Peng, W.; Li, B.; Qu, A.; Yao, X.; et al. Novel Metabolites Genetically Linked to Salt Sensitivity of Blood Pressure: Evidence from mGWAS in Chinese Population. Int. J. Mol. Sci. 2025, 26, 4538. https://doi.org/10.3390/ijms26104538
Yang X, Zhang B, Wen F, Qi H, Zhang F, Xie Y, Peng W, Li B, Qu A, Yao X, et al. Novel Metabolites Genetically Linked to Salt Sensitivity of Blood Pressure: Evidence from mGWAS in Chinese Population. International Journal of Molecular Sciences. 2025; 26(10):4538. https://doi.org/10.3390/ijms26104538
Chicago/Turabian StyleYang, Xiaojun, Bowen Zhang, Fuyuan Wen, Han Qi, Fengxu Zhang, Yunyi Xie, Wenjuan Peng, Boya Li, Aibin Qu, Xinyue Yao, and et al. 2025. "Novel Metabolites Genetically Linked to Salt Sensitivity of Blood Pressure: Evidence from mGWAS in Chinese Population" International Journal of Molecular Sciences 26, no. 10: 4538. https://doi.org/10.3390/ijms26104538
APA StyleYang, X., Zhang, B., Wen, F., Qi, H., Zhang, F., Xie, Y., Peng, W., Li, B., Qu, A., Yao, X., & Zhang, L. (2025). Novel Metabolites Genetically Linked to Salt Sensitivity of Blood Pressure: Evidence from mGWAS in Chinese Population. International Journal of Molecular Sciences, 26(10), 4538. https://doi.org/10.3390/ijms26104538